Carrel name: keyword-cov-cord Creating study carrel named keyword-cov-cord Initializing database file: cache/cord-024133-zv0ysi8m.json key: cord-024133-zv0ysi8m authors: Saxena, Shailendra K.; Kumar, Swatantra; Maurya, Vimal K.; Sharma, Raman; Dandu, Himanshu R.; Bhatt, Madan L. B. title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) date: 2020-04-30 journal: Coronavirus Disease 2019 (COVID-19) DOI: 10.1007/978-981-15-4814-7_1 sha: doc_id: 24133 cord_uid: zv0ysi8m file: cache/cord-025119-201ac32t.json key: cord-025119-201ac32t authors: Salman, Saad; Shah, Fahad H; Idrees, Jawaria; Idrees, Fariha; Velagala, Shreya; Ali, Johar; Khan, Abid A title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 journal: nan DOI: 10.2217/fvl-2020-0079 sha: doc_id: 25119 cord_uid: 201ac32t file: cache/cord-029813-o2uzcuai.json key: cord-029813-o2uzcuai authors: Rusconi, Stefano; Hayden, Frederick G title: COVID-19: studying the global pandemic – foreword date: 2020-07-27 journal: nan DOI: 10.2217/fvl-2020-0211 sha: doc_id: 29813 cord_uid: o2uzcuai file: cache/cord-031079-9lxhvyyb.json key: cord-031079-9lxhvyyb authors: Chen, Li; Chen, Haiyan; Dong, Shan; Huang, Wei; Chen, Li; Wei, Yuan; Shi, Liping; Li, Jinying; Zhu, Fengfeng; Zhu, Zhu; Wang, Yiyang; Lv, Xiuxiu; Yu, Xiaohui; Li, Hongmei; Wei, Wei; Zhang, Keke; Zhu, Lihong; Qu, Chen; Hong, Jian; Hu, Chaofeng; Dong, Jun; Qi, Renbin; Lu, Daxiang; Wang, Huadong; Peng, Shuang; Hao, Guang title: The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review date: 2020-07-27 journal: Function (Oxf) DOI: 10.1093/function/zqaa012 sha: doc_id: 31079 cord_uid: 9lxhvyyb file: cache/cord-124012-5zxkd2jy.json key: cord-124012-5zxkd2jy authors: Schwab, Patrick; Schutte, August DuMont; Dietz, Benedikt; Bauer, Stefan title: predCOVID-19: A Systematic Study of Clinical Predictive Models for Coronavirus Disease 2019 date: 2020-05-17 journal: nan DOI: nan sha: doc_id: 124012 cord_uid: 5zxkd2jy file: cache/cord-009476-4emc4o6n.json key: cord-009476-4emc4o6n authors: Madani, Tariq A title: Case definition and management of patients with MERS coronavirus in Saudi Arabia date: 2014-09-22 journal: Lancet Infect Dis DOI: 10.1016/s1473-3099(14)70918-1 sha: doc_id: 9476 cord_uid: 4emc4o6n file: cache/cord-193489-u6ewlh16.json key: cord-193489-u6ewlh16 authors: Wang, Rui; Hozumi, Yuta; Yin, Changchuan; Wei, Guo-Wei title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date: 2020-04-29 journal: nan DOI: nan sha: doc_id: 193489 cord_uid: u6ewlh16 file: cache/cord-257399-p6of5fno.json key: cord-257399-p6of5fno authors: Gentry, Chris A; Humphrey, Mary Beth; Thind, Sharanjeet K; Hendrickson, Sage C; Kurdgelashvili, George; Williams, Riley J title: Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study date: 2020-09-21 journal: Lancet Rheumatol DOI: 10.1016/s2665-9913(20)30305-2 sha: doc_id: 257399 cord_uid: p6of5fno file: cache/cord-015503-j99cgsjt.json key: cord-015503-j99cgsjt authors: Tang, Xiaolu; Wu, Changcheng; Li, Xiang; Song, Yuhe; Yao, Xinmin; Wu, Xinkai; Duan, Yuange; Zhang, Hong; Wang, Yirong; Qian, Zhaohui; Cui, Jie; Lu, Jian title: On the origin and continuing evolution of SARS-CoV-2 date: 2020-03-03 journal: Natl Sci Rev DOI: 10.1093/nsr/nwaa036 sha: doc_id: 15503 cord_uid: j99cgsjt file: cache/cord-019048-29wzpwvr.json key: cord-019048-29wzpwvr authors: Franks, Teri J.; Galvin, Jeffrey R. title: Coronavirus date: 2013-08-26 journal: Viruses and the Lung DOI: 10.1007/978-3-642-40605-8_13 sha: doc_id: 19048 cord_uid: 29wzpwvr file: cache/cord-029112-u507i0t0.json key: cord-029112-u507i0t0 authors: Smith, Keisha; Pace, Amy; Ortiz, Stephan; Kazani, Shamsah; Rottinghaus, Scott title: A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study protocol for a randomised controlled trial date: 2020-07-13 journal: Trials DOI: 10.1186/s13063-020-04548-z sha: doc_id: 29112 cord_uid: u507i0t0 file: cache/cord-032751-pmclolvh.json key: cord-032751-pmclolvh authors: Head, Katharine J.; Kasting, Monica L.; Sturm, Lynne A.; Hartsock, Jane A.; Zimet, Gregory D. title: A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts date: 2020-09-23 journal: Sci Commun DOI: 10.1177/1075547020960463 sha: doc_id: 32751 cord_uid: pmclolvh file: cache/cord-158628-71n1tgrw.json key: cord-158628-71n1tgrw authors: Russo, Giulia; Pennisi, Marzio; Viceconti, Marco; Pappalardo, Francesco title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform date: 2020-05-05 journal: nan DOI: nan sha: doc_id: 158628 cord_uid: 71n1tgrw file: cache/cord-252389-xrdbmosj.json key: cord-252389-xrdbmosj authors: Kumar, Mukesh; Thakur, Ajit Kumar title: Neurological manifestations and comorbidity associated with COVID-19: an overview date: 2020-10-14 journal: Neurol Sci DOI: 10.1007/s10072-020-04823-6 sha: doc_id: 252389 cord_uid: xrdbmosj file: cache/cord-033551-eojpkxz9.json key: cord-033551-eojpkxz9 authors: Shekh, Shamasoddin; Reddy, K. Kasi Amarnath; Gowd, Konkallu Hanumae title: In silico allicin induced S-thioallylation of SARS-CoV-2 main protease date: 2020-09-16 journal: nan DOI: 10.1080/17415993.2020.1817457 sha: doc_id: 33551 cord_uid: eojpkxz9 file: cache/cord-254446-yxqbe1dj.json key: cord-254446-yxqbe1dj authors: Ren, Yunzhao R.; Golding, Amit; Sorbello, Alfred; Ji, Ping; Chen, Jianmeng; Bhawana, Saluja; Witzmann, Kimberly; Arya, Vikram; Reynolds, Kellie S.; Choi, Su‐Young; Nikolov, Nikolay; Sahajwalla, Chandrahas title: A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19 date: 2020-05-29 journal: J Clin Pharmacol DOI: 10.1002/jcph.1673 sha: doc_id: 254446 cord_uid: yxqbe1dj file: cache/cord-031289-uxoz0xhk.json key: cord-031289-uxoz0xhk authors: Coccolini, Federico; Tartaglia, Dario; Puglisi, Adolfo; Giordano, Cesira; Pistello, Mauro; Lodato, Marianna; Chiarugi, Massimo title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients date: 2020-05-18 journal: Ann Surg DOI: 10.1097/sla.0000000000004030 sha: doc_id: 31289 cord_uid: uxoz0xhk file: cache/cord-032222-i6gfp4me.json key: cord-032222-i6gfp4me authors: Xue, Ling; Li, Jiao; Wei, Lin; Ma, Cuiqing title: A quick look at the latest developments in the COVID-19 pandemic date: 2020-09-10 journal: J Int Med Res DOI: 10.1177/0300060520943802 sha: doc_id: 32222 cord_uid: i6gfp4me file: cache/cord-150183-zzzyewjb.json key: cord-150183-zzzyewjb authors: Phillips, J. C. title: Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date: 2020-08-27 journal: nan DOI: nan sha: doc_id: 150183 cord_uid: zzzyewjb file: cache/cord-253457-gawn4s9g.json key: cord-253457-gawn4s9g authors: Yau, Kevin; Muller, Matthew P.; Lin, Molly; Siddiqui, Naureen; Neskovic, Sanja; Shokar, Gagan; Fattouh, Ramzi; Matukas, Larissa M.; Beaubien-Souligny, William; Thomas, Alison; Weinstein, Jordan J.; Zaltzman, Jeffrey; Wald, Ron title: COVID-19 Outbreak in an Urban Hemodialysis Unit date: 2020-07-15 journal: Am J Kidney Dis DOI: 10.1053/j.ajkd.2020.07.001 sha: doc_id: 253457 cord_uid: gawn4s9g file: cache/cord-254636-3lr008th.json key: cord-254636-3lr008th authors: Shishir, Tushar Ahmed; Naser, Iftekhar Bin; Faruque, Shah M. title: In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.07.20.212563 sha: doc_id: 254636 cord_uid: 3lr008th file: cache/cord-256146-d599uera.json key: cord-256146-d599uera authors: Kuiken, Thijs; Fouchier, Ron AM; Schutten, Martin; Rimmelzwaan, Guus F; van Amerongen, Geert; van Riel, Debby; Laman, Jon D; de Jong, Ton; van Doornum, Gerard; Lim, Wilina; Ling, Ai Ee; Chan, Paul KS; Tam, John S; Zambon, Maria C; Gopal, Robin; Drosten, Christian; van der Werf, Sylvie; Escriou, Nicolas; Manuguerra, Jean-Claude; Stöhr, Klaus; Peiris, J S Malik; Osterhaus, Albert DME title: Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome date: 2003-07-26 journal: Lancet DOI: 10.1016/s0140-6736(03)13967-0 sha: doc_id: 256146 cord_uid: d599uera file: cache/cord-252600-bvh1o64r.json key: cord-252600-bvh1o64r authors: Galasiti Kankanamalage, Anushka C.; Kim, Yunjeong; Damalanka, Vishnu C.; Rathnayake, Athri D.; Fehr, Anthony R.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Lushington, Gerald H.; Perlman, Stanley; Chang, Kyeong-Ok; Groutas, William C. title: Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element date: 2018-04-25 journal: European Journal of Medicinal Chemistry DOI: 10.1016/j.ejmech.2018.03.004 sha: doc_id: 252600 cord_uid: bvh1o64r file: cache/cord-104500-m0kfom0x.json key: cord-104500-m0kfom0x authors: Kyriakopoulos, Anthony M.; Papaefthymiou, Apostolis; Georgilas, Nikolaos; Doulberis, Michael; Kountouras, Jannis title: The Potential Role of Super Spread Events in SARS-COV-2 Pandemic; a Narrative Review date: 2020-09-21 journal: Arch Acad Emerg Med DOI: nan sha: doc_id: 104500 cord_uid: m0kfom0x file: cache/cord-253844-y6xdcf20.json key: cord-253844-y6xdcf20 authors: Yesudhas, Dhanusha; Srivastava, Ambuj; Gromiha, M. Michael title: COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date: 2020-09-04 journal: Infection DOI: 10.1007/s15010-020-01516-2 sha: doc_id: 253844 cord_uid: y6xdcf20 file: cache/cord-033780-184e64tr.json key: cord-033780-184e64tr authors: Smith, Rasheid; Geary, Sean M; Salem, Aliasger K title: Implications of current and future approaches to coronavirus disease 2019 testing date: 2020-10-13 journal: nan DOI: 10.2217/fvl-2020-0318 sha: doc_id: 33780 cord_uid: 184e64tr file: cache/cord-193133-puqcbf8t.json key: cord-193133-puqcbf8t authors: Piplani, Sakshi; Singh, Puneet Kumar; Winkler, David A.; Petrovsky, Nikolai title: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date: 2020-05-13 journal: nan DOI: nan sha: doc_id: 193133 cord_uid: puqcbf8t file: cache/cord-252767-as841xo0.json key: cord-252767-as841xo0 authors: Fischer, Bastian; Knabbe, Cornelius; Vollmer, Tanja title: SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 date: 2020-07-16 journal: Euro Surveill DOI: 10.2807/1560-7917.es.2020.25.28.2001285 sha: doc_id: 252767 cord_uid: as841xo0 file: cache/cord-256508-ce59ovan.json key: cord-256508-ce59ovan authors: Asselah, Tarik; Durantel, David; Pasmant, Eric; Lau, George; Schinazi, Raymond F. title: COVID-19: discovery, diagnostics and drug development date: 2020-10-08 journal: J Hepatol DOI: 10.1016/j.jhep.2020.09.031 sha: doc_id: 256508 cord_uid: ce59ovan file: cache/cord-256888-tdx12ccj.json key: cord-256888-tdx12ccj authors: Bradley, Benjamin T; Maioli, Heather; Johnston, Robert; Chaudhry, Irfan; Fink, Susan L; Xu, Haodong; Najafian, Behzad; Deutsch, Gail; Lacy, J Matthew; Williams, Timothy; Yarid, Nicole; Marshall, Desiree A title: Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series date: 2020-07-16 journal: Lancet DOI: 10.1016/s0140-6736(20)31305-2 sha: doc_id: 256888 cord_uid: tdx12ccj file: cache/cord-029547-9ei1ram3.json key: cord-029547-9ei1ram3 authors: Li, Jingwei; Shao, Jun; Wang, Chengdi; Li, Weimin title: The epidemiology and therapeutic options for the COVID-19 date: 2020-05-28 journal: Precis Clin Med DOI: 10.1093/pcmedi/pbaa017 sha: doc_id: 29547 cord_uid: 9ei1ram3 file: cache/cord-252232-vgq6gjpx.json key: cord-252232-vgq6gjpx authors: Hou, Yuxuan; Peng, Cheng; Yu, Meng; Li, Yan; Han, Zhenggang; Li, Fang; Wang, Lin-Fa; Shi, Zhengli title: Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry date: 2010-06-22 journal: Arch Virol DOI: 10.1007/s00705-010-0729-6 sha: doc_id: 252232 cord_uid: vgq6gjpx file: cache/cord-253905-zknmfgsh.json key: cord-253905-zknmfgsh authors: Li, Xingguang; Zai, Junjie; Zhao, Qiang; Nie, Qing; Li, Yi; Foley, Brian T.; Chaillon, Antoine title: Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 date: 2020-03-11 journal: J Med Virol DOI: 10.1002/jmv.25731 sha: doc_id: 253905 cord_uid: zknmfgsh file: cache/cord-024317-w1ep0wq8.json key: cord-024317-w1ep0wq8 authors: Ku, Zhiqiang; Ye, Xiaohua; Toa Salazar, Georgina; Zhang, Ningyan; An, Zhiqiang title: Antibody therapies for the treatment of COVID-19 date: 2020-04-30 journal: Antib Ther DOI: 10.1093/abt/tbaa007 sha: doc_id: 24317 cord_uid: w1ep0wq8 file: cache/cord-030934-t7akdu6x.json key: cord-030934-t7akdu6x authors: Bahrami, Afsane; Ferns, Gordon A title: Genetic and pathogenic characterization of SARS-CoV-2: a review date: 2020-08-26 journal: nan DOI: 10.2217/fvl-2020-0129 sha: doc_id: 30934 cord_uid: t7akdu6x file: cache/cord-252049-rgdynmla.json key: cord-252049-rgdynmla authors: Tomar, Sakshi; Johnston, Melanie L.; St. John, Sarah E.; Osswald, Heather L.; Nyalapatla, Prasanth R.; Paul, Lake N.; Ghosh, Arun K.; Denison, Mark R.; Mesecar, Andrew D. title: Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS date: 2015-06-08 journal: Journal of Biological Chemistry DOI: 10.1074/jbc.m115.651463 sha: doc_id: 252049 cord_uid: rgdynmla file: cache/cord-256020-wrui3i2l.json key: cord-256020-wrui3i2l authors: Fadaka, Adewale Oluwaseun; Sibuyi, Nicole Remaliah Samantha; Adewale, Olusola Bolaji; Bakare, Olalekan Olanrewaju; Akanbi, Musa Oyebowale; Klein, Ashwil; Madiehe, Abram Madimabe; Meyer, Mervin title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 journal: J Int Med Res DOI: 10.1177/0300060520949077 sha: doc_id: 256020 cord_uid: wrui3i2l file: cache/cord-214854-ck61ja2t.json key: cord-214854-ck61ja2t authors: Zhong, Jing; Roesch, Enja Laureen; Viereck, Thilo; Schilling, Meinhard; Ludwig, Frank title: Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles date: 2020-10-08 journal: nan DOI: nan sha: doc_id: 214854 cord_uid: ck61ja2t file: cache/cord-254395-tu4aqczj.json key: cord-254395-tu4aqczj authors: Froggatt, Heather M.; Heaton, Brook E.; Heaton, Nicholas S. title: Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CL(pro) Reporter Assay date: 2020-10-27 journal: J Virol DOI: 10.1128/jvi.01265-20 sha: doc_id: 254395 cord_uid: tu4aqczj file: cache/cord-256217-fnjer0e0.json key: cord-256217-fnjer0e0 authors: Neri, Piergiorgio; Pichi, Francesco title: COVID-19 and the eye immunity: lesson learned from the past and possible new therapeutic insights date: 2020-04-20 journal: Int Ophthalmol DOI: 10.1007/s10792-020-01389-2 sha: doc_id: 256217 cord_uid: fnjer0e0 file: cache/cord-256737-ptjng78b.json key: cord-256737-ptjng78b authors: McBride, Corrin E.; Machamer, Carolyn E. title: Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein date: 2010-09-01 journal: Virology DOI: 10.1016/j.virol.2010.05.031 sha: doc_id: 256737 cord_uid: ptjng78b file: cache/cord-258268-7ypq0t3d.json key: cord-258268-7ypq0t3d authors: Zanin, Luca; Saraceno, Giorgio; Panciani, Pier Paolo; Renisi, Giulia; Signorini, Liana; Migliorati, Karol; Fontanella, Marco Maria title: SARS-CoV-2 can induce brain and spine demyelinating lesions date: 2020-05-04 journal: Acta Neurochir (Wien) DOI: 10.1007/s00701-020-04374-x sha: doc_id: 258268 cord_uid: 7ypq0t3d file: cache/cord-034354-4xu97je3.json key: cord-034354-4xu97je3 authors: Wang, Hongye; Wu, Xian; Zhang, Xiaomei; Hou, Xin; Liang, Te; Wang, Dan; Teng, Fei; Dai, Jiayu; Duan, Hu; Guo, Shubin; Li, Yongzhe; Yu, Xiaobo title: SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution date: 2020-10-21 journal: ACS Cent Sci DOI: 10.1021/acscentsci.0c00742 sha: doc_id: 34354 cord_uid: 4xu97je3 file: cache/cord-253862-jl1zhg13.json key: cord-253862-jl1zhg13 authors: Khalaf, Khalil; Papp, Natalia; Chou, Jadzia Tin-Tsen; Hana, Doris; Mackiewicz, Andrzej; Kaczmarek, Mariusz title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.570927 sha: doc_id: 253862 cord_uid: jl1zhg13 file: cache/cord-254968-czrgzyr3.json key: cord-254968-czrgzyr3 authors: Zhang, Qiang; Zhang, Huajun; Gao, Jindong; Huang, Kun; Yang, Yong; Hui, Xianfeng; He, Xinglin; Li, Chengfei; Gong, Wenxiao; Zhang, Yufei; Zhao, Ya; Peng, Cheng; Gao, Xiaoxiao; Chen, Huanchun; Zou, Zhong; Shi, Zheng-Li; Jin, Meilin title: A serological survey of SARS-CoV-2 in cat in Wuhan date: 2020-09-17 journal: Emerging microbes & infections DOI: 10.1080/22221751.2020.1817796 sha: doc_id: 254968 cord_uid: czrgzyr3 file: cache/cord-255552-k1retwa4.json key: cord-255552-k1retwa4 authors: Gassen, Nils C.; Papies, Jan; Bajaj, Thomas; Dethloff, Frederik; Emanuel, Jackson; Weckmann, Katja; Heinz, Daniel E.; Heinemann, Nicolas; Lennarz, Martina; Richter, Anja; Niemeyer, Daniela; Corman, Victor M.; Giavalisco, Patrick; Drosten, Christian; Müller, Marcel A. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 journal: bioRxiv DOI: 10.1101/2020.04.15.997254 sha: doc_id: 255552 cord_uid: k1retwa4 file: cache/cord-255815-5d9bqji0.json key: cord-255815-5d9bqji0 authors: Malik, Ajamaluddin; Alsenaidy, Mohammad A. title: MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization date: 2017-05-30 journal: 3 Biotech DOI: 10.1007/s13205-017-0744-3 sha: doc_id: 255815 cord_uid: 5d9bqji0 file: cache/cord-255883-mz6nyisw.json key: cord-255883-mz6nyisw authors: Asif, Muhammad; Saleem, Mohammad; Saadullah, Malik; Yaseen, Hafiza Sidra; Al Zarzour, Raghdaa title: COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties date: 2020-08-14 journal: Inflammopharmacology DOI: 10.1007/s10787-020-00744-0 sha: doc_id: 255883 cord_uid: mz6nyisw file: cache/cord-255997-oer5lxxr.json key: cord-255997-oer5lxxr authors: Onodi, Fanny; Bonnet-Madin, Lucie; Karpf, Léa; Meertens, Laurent; Poirot, Justine; Legoff, Jérome; Delaugerre, Constance; Amara, Ali; Soumelis, Vassili title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 journal: bioRxiv DOI: 10.1101/2020.07.10.197343 sha: doc_id: 255997 cord_uid: oer5lxxr file: cache/cord-258881-74aijckl.json key: cord-258881-74aijckl authors: Wang, Maomao; Luo, Limin; Bu, Haiji; Xia, Hu title: Case Report: One Case of Coronavirus Desease 2019(COVID-19) in Patient Co-nfected by HIV With a Low CD4+ T Cell Count date: 2020-04-23 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.04.060 sha: doc_id: 258881 cord_uid: 74aijckl file: cache/cord-259229-e8m8m4ut.json key: cord-259229-e8m8m4ut authors: Samidurai, Arun; Das, Anindita title: Cardiovascular Complications Associated with COVID-19 and Potential Therapeutic Strategies date: 2020-09-16 journal: Int J Mol Sci DOI: 10.3390/ijms21186790 sha: doc_id: 259229 cord_uid: e8m8m4ut file: cache/cord-254469-7q6xi2xx.json key: cord-254469-7q6xi2xx authors: Wang, Fuzhou; Kream, Richard M.; Stefano, George B. title: An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development date: 2020-05-05 journal: Med Sci Monit DOI: 10.12659/msm.924700 sha: doc_id: 254469 cord_uid: 7q6xi2xx file: cache/cord-259603-bh198xgl.json key: cord-259603-bh198xgl authors: Snijder, E.J.; Decroly, E.; Ziebuhr, J. title: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date: 2016-09-14 journal: Adv Virus Res DOI: 10.1016/bs.aivir.2016.08.008 sha: doc_id: 259603 cord_uid: bh198xgl file: cache/cord-257958-yehnlabq.json key: cord-257958-yehnlabq authors: Barh, Debmalya; Tiwari, Sandeep; Weener, Marianna E.; Azevedo, Vasco; Góes-Neto, Aristóteles; Gromiha, M. Michael; Ghosh, Preetam title: Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19 date: 2020-10-10 journal: Comput Biol Med DOI: 10.1016/j.compbiomed.2020.104051 sha: doc_id: 257958 cord_uid: yehnlabq file: cache/cord-258914-g6pv8zz9.json key: cord-258914-g6pv8zz9 authors: Proud, Pamela C.; Tsitoura, Daphne; Watson, Robert J.; Chua, Brendon Y; Aram, Marilyn J.; Bewley, Kevin R.; Cavell, Breeze E.; Cobb, Rebecca; Dowall, Stuart; Fotheringham, Susan A.; Ho, Catherine M. K.; Lucas, Vanessa; Ngabo, Didier; Rayner, Emma; Ryan, Kathryn A.; Slack, Gillian S.; Thomas, Stephen; Wand, Nadina I.; Yeates, Paul; Demaison, Christophe; Jackson, David C.; Bartlett, Nathan W.; Mercuri, Francesca; Carroll, Miles W. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 journal: bioRxiv DOI: 10.1101/2020.09.25.309914 sha: doc_id: 258914 cord_uid: g6pv8zz9 file: cache/cord-258312-3v5t4k8d.json key: cord-258312-3v5t4k8d authors: Majachani, Nicole; Francois, Jean Luc M.; Fernando, Ashen K.; Zuberi, Jamshed title: A Case of a Newborn Baby Girl Infected with SARS-CoV-2 Due to Transplacental Viral Transmission date: 2020-10-25 journal: Am J Case Rep DOI: 10.12659/ajcr.925766 sha: doc_id: 258312 cord_uid: 3v5t4k8d file: cache/cord-258595-bk35vxlr.json key: cord-258595-bk35vxlr authors: Westhaus, Sandra; Weber, Frank-Andreas; Schiwy, Sabrina; Linnemann, Volker; Brinkmann, Markus; Widera, Marek; Greve, Carola; Janke, Axel; Hollert, Henner; Wintgens, Thomas; Ciesek, Sandra title: Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks date: 2020-08-18 journal: Sci Total Environ DOI: 10.1016/j.scitotenv.2020.141750 sha: doc_id: 258595 cord_uid: bk35vxlr file: cache/cord-262328-q7mt0xve.json key: cord-262328-q7mt0xve authors: Wajnberg, Ania; Mansour, Mayce; Leven, Emily; Bouvier, Nicole M; Patel, Gopi; Firpo-Betancourt, Adolfo; Mendu, Rao; Jhang, Jeffrey; Arinsburg, Suzanne; Gitman, Melissa; Houldsworth, Jane; Sordillo, Emilia; Paniz-Mondolfi, Alberto; Baine, Ian; Simon, Viviana; Aberg, Judith; Krammer, Florian; Reich, David; Cordon-Cardo, Carlos title: Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study date: 2020-09-25 journal: Lancet Microbe DOI: 10.1016/s2666-5247(20)30120-8 sha: doc_id: 262328 cord_uid: q7mt0xve file: cache/cord-253665-1dn3ek34.json key: cord-253665-1dn3ek34 authors: Vishnubalaji, Radhakrishnan; Shaath, Hibah; Alajez, Nehad M. title: Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response date: 2020-07-07 journal: Genes (Basel) DOI: 10.3390/genes11070760 sha: doc_id: 253665 cord_uid: 1dn3ek34 file: cache/cord-260729-b12v3c8c.json key: cord-260729-b12v3c8c authors: de Lang, Anna; Baas, Tracey; Teal, Thomas; Leijten, Lonneke M; Rain, Brandon; Osterhaus, Albert D; Haagmans, Bart L; Katze, Michael G title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date: 2007-08-10 journal: PLoS Pathog DOI: 10.1371/journal.ppat.0030112 sha: doc_id: 260729 cord_uid: b12v3c8c file: cache/cord-261718-zqoggwnk.json key: cord-261718-zqoggwnk authors: Pietschmann, Jan; Vöpel, Nadja; Spiegel, Holger; Krause, Hans-Joachim; Schröper, Florian title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 journal: bioRxiv DOI: 10.1101/2020.06.02.131102 sha: doc_id: 261718 cord_uid: zqoggwnk file: cache/cord-265128-i0d4lxko.json key: cord-265128-i0d4lxko authors: Gurung, Arun Bahadur; Ali, Mohammad Ajmal; Lee, Joongku; Farah, Mohammad Abul; Al-Anazi, Khalid Mashay title: Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach date: 2020-05-22 journal: Life Sci DOI: 10.1016/j.lfs.2020.117831 sha: doc_id: 265128 cord_uid: i0d4lxko file: cache/cord-265322-3854ddb9.json key: cord-265322-3854ddb9 authors: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109759 sha: doc_id: 265322 cord_uid: 3854ddb9 file: cache/cord-262276-5nue46dm.json key: cord-262276-5nue46dm authors: Roussel, Yanis; Giraud-Gatineau, Audrey; Jimeno, Marie-Thérèse; Rolain, Jean-Marc; Zandotti, Christine; Colson, Philippe; Raoult, Didier title: SARS-CoV-2: fear versus data date: 2020-03-19 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.105947 sha: doc_id: 262276 cord_uid: 5nue46dm file: cache/cord-261075-wqtxhiy8.json key: cord-261075-wqtxhiy8 authors: Zhang, Meng; Zhou, Lingyan; Wang, Jing; Wang, Kun; Wang, Yuan; Pan, Xudong; Ma, Aijun title: The nervous system——a new territory being explored of SARS-CoV-2 date: 2020-10-28 journal: J Clin Neurosci DOI: 10.1016/j.jocn.2020.10.056 sha: doc_id: 261075 cord_uid: wqtxhiy8 file: cache/cord-266511-g5h4tazp.json key: cord-266511-g5h4tazp authors: Deslandes, A; Berti, V; Tandjaoui-Lambotte, Y; Alloui, Chakib; Carbonnelle, E; Zahar, JR; Brichler, S; Cohen, Yves title: SARS-COV-2 was already spreading in France in late December 2019 date: 2020-05-03 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.106006 sha: doc_id: 266511 cord_uid: g5h4tazp file: cache/cord-252456-971d0sir.json key: cord-252456-971d0sir authors: Hemida, Maged Gomaa; Ba Abduallah, Mohammed M. title: The SARS-CoV-2 outbreak from a one health perspective date: 2020-03-16 journal: One Health DOI: 10.1016/j.onehlt.2020.100127 sha: doc_id: 252456 cord_uid: 971d0sir file: cache/cord-261566-fn08b0y2.json key: cord-261566-fn08b0y2 authors: Mudgal, Rajat; Nehul, Sanketkumar; Tomar, Shailly title: Prospects for mucosal vaccine: shutting the door on SARS-CoV-2 date: 2020-09-15 journal: Human vaccines & immunotherapeutics DOI: 10.1080/21645515.2020.1805992 sha: doc_id: 261566 cord_uid: fn08b0y2 file: cache/cord-264267-weat0qs6.json key: cord-264267-weat0qs6 authors: Kleine-Weber, Hannah; Schroeder, Simon; Krüger, Nadine; Prokscha, Alexander; Naim, Hassan Y.; Müller, Marcel A.; Drosten, Christian; Pöhlmann, Stefan; Hoffmann, Markus title: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus date: 2020-01-21 journal: Emerg Microbes Infect DOI: 10.1080/22221751.2020.1713705 sha: doc_id: 264267 cord_uid: weat0qs6 file: cache/cord-265329-bsypo08l.json key: cord-265329-bsypo08l authors: van Dorp, Lucy; Acman, Mislav; Richard, Damien; Shaw, Liam P.; Ford, Charlotte E.; Ormond, Louise; Owen, Christopher J.; Pang, Juanita; Tan, Cedric C.S.; Boshier, Florencia A.T.; Ortiz, Arturo Torres; Balloux, François title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 date: 2020-05-05 journal: Infect Genet Evol DOI: 10.1016/j.meegid.2020.104351 sha: doc_id: 265329 cord_uid: bsypo08l file: cache/cord-262266-m0fjt483.json key: cord-262266-m0fjt483 authors: Peddu, Vikas; Shean, Ryan C; Xie, Hong; Shrestha, Lasata; Perchetti, Garrett A; Minot, Samuel S; Roychoudhury, Pavitra; Huang, Meei-Li; Nalla, Arun; Reddy, Shriya B; Phung, Quynh; Reinhardt, Adam; Jerome, Keith R; Greninger, Alexander L title: Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization date: 2020-05-07 journal: Clin Chem DOI: 10.1093/clinchem/hvaa106 sha: doc_id: 262266 cord_uid: m0fjt483 file: cache/cord-264031-0y7xbgun.json key: cord-264031-0y7xbgun authors: Wierbowski, Shayne D.; Liang, Siqi; Chen, You; Andre, Nicole M.; Lipkin, Steven M.; Whittaker, Gary R.; Yu, Haiyuan title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 journal: bioRxiv DOI: 10.1101/2020.10.13.308676 sha: doc_id: 264031 cord_uid: 0y7xbgun file: cache/cord-266348-tbr2ynx0.json key: cord-266348-tbr2ynx0 authors: Stroemer, A.; Grobe, O.; Rose, R.; Fickenscher, H.; Lorentz, T.; Krumbholz, A. title: Diagnostic accuracy of six commercial SARS-CoV-2 IgG/total antibody assays and identification of SARS-CoV-2 neutralizing antibodies in convalescent sera date: 2020-06-17 journal: nan DOI: 10.1101/2020.06.15.20131672 sha: doc_id: 266348 cord_uid: tbr2ynx0 file: cache/cord-260508-z11exbyu.json key: cord-260508-z11exbyu authors: Wang, Hongru; Pipes, Lenore; Nielsen, Rasmus title: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.04.20.052019 sha: doc_id: 260508 cord_uid: z11exbyu file: cache/cord-262119-s6hc7fxs.json key: cord-262119-s6hc7fxs authors: Ostaszewski, Marek; Niarakis, Anna; Mazein, Alexander; Kuperstein, Inna; Phair, Robert; Orta-Resendiz, Aurelio; Singh, Vidisha; Aghamiri, Sara Sadat; Acencio, Marcio Luis; Glaab, Enrico; Ruepp, Andreas; Fobo, Gisela; Montrone, Corinna; Brauner, Barbara; Frischman, Goar; Monraz Gómez, Luis Cristóbal; Somers, Julia; Hoch, Matti; Gupta, Shailendra Kumar; Scheel, Julia; Borlinghaus, Hanna; Czauderna, Tobias; Schreiber, Falk; Montagud, Arnau; de Leon, Miguel Ponce; Funahashi, Akira; Hiki, Yusuke; Hiroi, Noriko; Yamada, Takahiro G.; Dräger, Andreas; Renz, Alina; Naveez, Muhammad; Bocskei, Zsolt; Messina, Francesco; Börnigen, Daniela; Fergusson, Liam; Conti, Marta; Rameil, Marius; Nakonecnij, Vanessa; Vanhoefer, Jakob; Schmiester, Leonard; Wang, Muying; Ackerman, Emily E.; Shoemaker, Jason; Zucker, Jeremy; Oxford, Kristie; Teuton, Jeremy; Kocakaya, Ebru; Summak, Gökçe Yağmur; Hanspers, Kristina; Kutmon, Martina; Coort, Susan; Eijssen, Lars; Ehrhart, Friederike; Rex, D. A. B.; Slenter, Denise; Martens, Marvin; Haw, Robin; Jassal, Bijay; Matthews, Lisa; Orlic-Milacic, Marija; Senff Ribeiro, Andrea; Rothfels, Karen; Shamovsky, Veronica; Stephan, Ralf; Sevilla, Cristoffer; Varusai, Thawfeek; Ravel, Jean-Marie; Fraser, Rupsha; Ortseifen, Vera; Marchesi, Silvia; Gawron, Piotr; Smula, Ewa; Heirendt, Laurent; Satagopam, Venkata; Wu, Guanming; Riutta, Anders; Golebiewski, Martin; Owen, Stuart; Goble, Carole; Hu, Xiaoming; Overall, Rupert W.; Maier, Dieter; Bauch, Angela; Gyori, Benjamin M.; Bachman, John A.; Vega, Carlos; Grouès, Valentin; Vazquez, Miguel; Porras, Pablo; Licata, Luana; Iannuccelli, Marta; Sacco, Francesca; Nesterova, Anastasia; Yuryev, Anton; de Waard, Anita; Turei, Denes; Luna, Augustin; Babur, Ozgun; Soliman, Sylvain; Valdeolivas, Alberto; Esteban-Medina, Marina; Peña-Chilet, Maria; Helikar, Tomáš; Puniya, Bhanwar Lal; Modos, Dezso; Treveil, Agatha; Olbei, Marton; De Meulder, Bertrand; Dugourd, Aurélien; Naldi, Aurelien; Noel, Vincent; Calzone, Laurence; Sander, Chris; Demir, Emek; Korcsmaros, Tamas; Freeman, Tom C.; Augé, Franck; Beckmann, Jacques S.; Hasenauer, Jan; Wolkenhauer, Olaf; Wilighagen, Egon L.; Pico, Alexander R.; Evelo, Chris T.; Gillespie, Marc E.; Stein, Lincoln D.; Hermjakob, Henning; D’Eustachio, Peter; Saez-Rodriguez, Julio; Dopazo, Joaquin; Valencia, Alfonso; Kitano, Hiroaki; Barillot, Emmanuel; Auffray, Charles; Balling, Rudi; Schneider, Reinhard title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 journal: bioRxiv DOI: 10.1101/2020.10.26.356014 sha: doc_id: 262119 cord_uid: s6hc7fxs file: cache/cord-263481-w5ytp1q7.json key: cord-263481-w5ytp1q7 authors: Lokman, Syed Mohammad; Rasheduzzaman, M.D.; Salauddin, Asma; Barua, Rocktim; Tanzina, Afsana Yeasmin; Rumi, Meheadi Hasan; Hossain, M.D. Imran; Siddiki, A.M.A.M. Zonaed; Mannan, Adnan; Hasan, M.D. Mahbub title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach date: 2020-06-02 journal: Infect Genet Evol DOI: 10.1016/j.meegid.2020.104389 sha: doc_id: 263481 cord_uid: w5ytp1q7 file: cache/cord-257105-vrwuaknf.json key: cord-257105-vrwuaknf authors: Davies, Julie; Randeva, Harpal S.; Chatha, Kamaljit; Hall, Marcia; Spandidos, Demetrios A.; Karteris, Emmanouil; Kyrou, Ioannis title: Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19 date: 2020-09-15 journal: Mol Med Rep DOI: 10.3892/mmr.2020.11510 sha: doc_id: 257105 cord_uid: vrwuaknf file: cache/cord-262045-r2iqpmmc.json key: cord-262045-r2iqpmmc authors: Smits, Saskia L.; Raj, V. Stalin; Pas, Suzan D.; Reusken, Chantal B.E.M.; Mohran, Khaled; Farag, Elmoubasher A.B.A.; Al-Romaihi, Hamad E.; AlHajri, Mohd M.; Haagmans, Bart L.; Koopmans, Marion P. title: Reliable typing of MERS-CoV variants with a small genome fragment date: 2014-12-15 journal: J Clin Virol DOI: 10.1016/j.jcv.2014.12.006 sha: doc_id: 262045 cord_uid: r2iqpmmc file: cache/cord-265366-vmuqbpkk.json key: cord-265366-vmuqbpkk authors: Leibowitz, Jill; Krief, William; Barone, Stephen; Williamson, Kristy A.; Goenka, Pratichi K.; Rai, Shipra; Moriarty, Shannon; Baodhankar, Prachi; Rubin, Lorry G. title: Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without SARS-CoV-2 Infection date: 2020-10-09 journal: J Pediatr DOI: 10.1016/j.jpeds.2020.10.002 sha: doc_id: 265366 cord_uid: vmuqbpkk file: cache/cord-254916-y1rw9q11.json key: cord-254916-y1rw9q11 authors: Ogando, Natacha S.; Dalebout, Tim J.; Zevenhoven-Dobbe, Jessika C.; Limpens, Ronald W.A.L.; van der Meer, Yvonne; Caly, Leon; Druce, Julian; de Vries, Jutte J. C.; Kikkert, Marjolein; Bárcena, Montserrat; Sidorov, Igor; Snijder, Eric J. title: SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology date: 2020-06-22 journal: J Gen Virol DOI: 10.1099/jgv.0.001453 sha: doc_id: 254916 cord_uid: y1rw9q11 file: cache/cord-262786-otxpc46a.json key: cord-262786-otxpc46a authors: Mohammadi, Soheil; Moosaie, Fatemeh; Aarabi, Mohammad Hadi title: Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms date: 2020-09-01 journal: Mol Neurobiol DOI: 10.1007/s12035-020-02094-y sha: doc_id: 262786 cord_uid: otxpc46a file: cache/cord-262958-tmp6yxlv.json key: cord-262958-tmp6yxlv authors: Pinto, Dora; Park, Young-Jun; Beltramello, Martina; Walls, Alexandra C.; Tortorici, M. Alejandra; Bianchi, Siro; Jaconi, Stefano; Culap, Katja; Zatta, Fabrizia; De Marco, Anna; Peter, Alessia; Guarino, Barbara; Spreafico, Roberto; Cameroni, Elisabetta; Case, James Brett; Chen, Rita E.; Havenar-Daughton, Colin; Snell, Gyorgy; Telenti, Amalio; Virgin, Herbert W.; Lanzavecchia, Antonio; Diamond, Michael S.; Fink, Katja; Veesler, David; Corti, Davide title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody date: 2020-04-09 journal: bioRxiv DOI: 10.1101/2020.04.07.023903 sha: doc_id: 262958 cord_uid: tmp6yxlv file: cache/cord-263945-yli5suxb.json key: cord-263945-yli5suxb authors: Iancu, Gabriela Mariana; Solomon, Adelaida; Birlutiu, Victoria title: Viral exanthema as manifestation of SARS-CoV-2 infection: A case report date: 2020-08-28 journal: Medicine (Baltimore) DOI: 10.1097/md.0000000000021810 sha: doc_id: 263945 cord_uid: yli5suxb file: cache/cord-264814-v4wnmg03.json key: cord-264814-v4wnmg03 authors: Flanagan, Katie L.; Best, Emma; Crawford, Nigel W.; Giles, Michelle; Koirala, Archana; Macartney, Kristine; Russell, Fiona; Teh, Benjamin W.; Wen, Sophie CH title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 journal: Front Immunol DOI: 10.3389/fimmu.2020.579250 sha: doc_id: 264814 cord_uid: v4wnmg03 file: cache/cord-266156-xmf4emln.json key: cord-266156-xmf4emln authors: Miller, Tyler E.; Garcia Beltran, Wilfredo F.; Bard, Adam Z.; Gogakos, Tasos; Anahtar, Melis N.; Astudillo, Michael Gerino; Yang, Diane; Thierauf, Julia; Fisch, Adam S.; Mahowald, Grace K.; Fitzpatrick, Megan J.; Nardi, Valentina; Feldman, Jared; Hauser, Blake M.; Caradonna, Timothy M.; Marble, Hetal D.; Ritterhouse, Lauren L.; Turbett, Sara E.; Batten, Julie; Georgantas, Nicholas Zeke; Alter, Galit; Schmidt, Aaron G.; Harris, Jason B.; Gelfand, Jeffrey A.; Poznansky, Mark C.; Bernstein, Bradley E.; Louis, David N.; Dighe, Anand; Charles, Richelle C.; Ryan, Edward T.; Branda, John A.; Pierce, Virginia M.; Murali, Mandakolathur R.; Iafrate, A. John; Rosenberg, Eric S.; Lennerz, Jochen K. title: Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital date: 2020-08-28 journal: FASEB J DOI: 10.1096/fj.202001700rr sha: doc_id: 266156 cord_uid: xmf4emln file: cache/cord-266885-a5fdeuvv.json key: cord-266885-a5fdeuvv authors: Dlotko, P.; Rudkin, S. title: Covid-19 clinical data analysis using Ball Mapper date: 2020-04-15 journal: nan DOI: 10.1101/2020.04.10.20061374 sha: doc_id: 266885 cord_uid: a5fdeuvv file: cache/cord-267115-6jqdi417.json key: cord-267115-6jqdi417 authors: Giobbe, Giovanni Giuseppe; Bonfante, Francesco; Zambaiti, Elisa; Gagliano, Onelia; Jones, Brendan C.; Luni, Camilla; Laterza, Cecilia; Perin, Silvia; Stuart, Hannah T.; Pagliari, Matteo; Bortolami, Alessio; Mazzetto, Eva; Manfredi, Anna; Colantuono, Chiara; Di Filippo, Lucio; Pellegata, Alessandro; Li, Vivian Sze Wing; Eaton, Simon; Thapar, Nikhil; Cacchiarelli, Davide; Elvassore, Nicola; De Coppi, Paolo title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.24.167049 sha: doc_id: 267115 cord_uid: 6jqdi417 file: cache/cord-267134-5gz2dotn.json key: cord-267134-5gz2dotn authors: Sallenave, Jean-Michel; Guillot, Loïc title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date: 2020-05-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.01229 sha: doc_id: 267134 cord_uid: 5gz2dotn file: cache/cord-267782-4pjfnund.json key: cord-267782-4pjfnund authors: Lan, Fan-Yun; Suharlim, Christian; Kales, Stefanos N; Yang, Justin title: Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the USA date: 2020-10-30 journal: Occup Environ Med DOI: 10.1136/oemed-2020-106774 sha: doc_id: 267782 cord_uid: 4pjfnund file: cache/cord-267458-uofy7jyx.json key: cord-267458-uofy7jyx authors: Jiang, Xiao-Lin; Zhang, Xiao-Li; Zhao, Xiang-Na; Li, Cun-Bao; Lei, Jie; Kou, Zeng-Qiang; Sun, Wen-Kui; Hang, Yang; Gao, Feng; Ji, Sheng-Xiang; Lin, Can-Fang; Pang, Bo; Yao, Ming-Xiao; Anderson, Benjamin D; Wang, Guo-Lin; Yao, Lin; Duan, Li-Jun; Kang, Dian-Ming; Ma, Mai-Juan title: Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China date: 2020-04-22 journal: J Infect Dis DOI: 10.1093/infdis/jiaa206 sha: doc_id: 267458 cord_uid: uofy7jyx file: cache/cord-260048-yis26g81.json key: cord-260048-yis26g81 authors: McNamara, Ryan P.; Caro-Vegas, Carolina; Landis, Justin T.; Moorad, Razia; Pluta, Linda J.; Eason, Anthony B.; Thompson, Cecilia; Bailey, Aubrey; Villamor, Femi Cleola S.; Lange, Philip T.; Wong, Jason P.; Seltzer, Tischan; Seltzer, Jedediah; Zhou, Yijun; Vahrson, Wolfgang; Juarez, Angelica; Meyo, James O.; Calabre, Tiphaine; Broussard, Grant; Rivera-Soto, Ricardo; Chappell, Danielle L.; Baric, Ralph S.; Damania, Blossom; Miller, Melissa B.; Dittmer, Dirk P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-10-20 journal: Cell Rep DOI: 10.1016/j.celrep.2020.108352 sha: doc_id: 260048 cord_uid: yis26g81 file: cache/cord-266444-rw94yls8.json key: cord-266444-rw94yls8 authors: Dominguez Andres, Ana; Feng, Yongmei; Campos, Alexandre Rosa; Yin, Jun; Yang, Chih-Cheng; James, Brian; Murad, Rabi; Kim, Hyungsoo; Deshpande, Aniruddha J.; Gordon, David E.; Krogan, Nevan; Pippa, Raffaella; Ronai, Ze’ev A. title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 journal: bioRxiv DOI: 10.1101/2020.08.18.256776 sha: doc_id: 266444 cord_uid: rw94yls8 file: cache/cord-263532-q044i7ym.json key: cord-263532-q044i7ym authors: Goyal, Bhupesh; Goyal, Deepti title: Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy date: 2020-05-13 journal: ACS Comb Sci DOI: 10.1021/acscombsci.0c00058 sha: doc_id: 263532 cord_uid: q044i7ym file: cache/cord-266987-ikt8r2o1.json key: cord-266987-ikt8r2o1 authors: Loeffelholz, Michael J.; Tang, Yi-Wei title: Laboratory diagnosis of emerging human coronavirus infections – the state of the art date: 2020-03-30 journal: Emerg Microbes Infect DOI: 10.1080/22221751.2020.1745095 sha: doc_id: 266987 cord_uid: ikt8r2o1 file: cache/cord-264968-ctx39vhi.json key: cord-264968-ctx39vhi authors: Woo, Patrick CY; Lau, Susanna KP; Tsoi, Hoi-wah; Chan, Kwok-hung; Wong, Beatrice HL; Che, Xiao-yan; Tam, Victoria KP; Tam, Sidney CF; Cheng, Vincent CC; Hung, Ivan FN; Wong, Samson SY; Zheng, Bo-jian; Guan, Yi; Yuen, Kwok-yung title: Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia date: 2004-03-13 journal: Lancet DOI: 10.1016/s0140-6736(04)15729-2 sha: doc_id: 264968 cord_uid: ctx39vhi file: cache/cord-267770-ik1ib3zb.json key: cord-267770-ik1ib3zb authors: Koo, Hyun Jung; Choi, Sang-Ho; Sung, Heungsup; Choe, Jooae; Do, Kyung-Hyun title: RadioGraphics Update: Radiographic and CT Features of Viral Pneumonia date: 2020-06-05 journal: Radiographics DOI: 10.1148/rg.2020200097 sha: doc_id: 267770 cord_uid: ik1ib3zb file: cache/cord-268468-036i1082.json key: cord-268468-036i1082 authors: Asif, Muhammad; Ajmal, Muhammad; Ashraf, Ghazala; Muhammad, Nadeem; Aziz, Ayesha; Iftikhar, Tayyaba; Wang, Junlei; Liu, Hongfang title: The role of biosensors in COVID-19 outbreak date: 2020-09-18 journal: Curr Opin Electrochem DOI: 10.1016/j.coelec.2020.08.011 sha: doc_id: 268468 cord_uid: 036i1082 file: cache/cord-267887-ntwvquqz.json key: cord-267887-ntwvquqz authors: Yang, Ren; Huang, Baoying; Ruhan, A.; Li, Wenhui; Wang, Wenling; Deng, Yao; Tan, Wenjie title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro date: 2020-08-21 journal: Biosaf Health DOI: 10.1016/j.bsheal.2020.08.004 sha: doc_id: 267887 cord_uid: ntwvquqz file: cache/cord-268034-7id7sfsu.json key: cord-268034-7id7sfsu authors: Auerswald, Heidi; 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Masudur; Elshabrawy, Hatem A. title: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks date: 2020-03-04 journal: Pathogens DOI: 10.3390/pathogens9030186 sha: doc_id: 271648 cord_uid: m2c5bvuj file: cache/cord-268540-wrjzr3ws.json key: cord-268540-wrjzr3ws authors: Park, You Jeong; Farooq, Jeffrey; Cho, Justin; Sadanandan, Nadia; Cozene, Blaise; Gonzales-Portillo, Bella; Saft, Madeline; Borlongan, Maximillian C.; Borlongan, Mia C.; Shytle, R. Douglas; Willing, Alison E.; Garbuzova-Davis, Svitlana; Sanberg, Paul R.; Borlongan, Cesar V. title: Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics date: 2020-08-13 journal: Stem Cell Rev Rep DOI: 10.1007/s12015-020-10026-5 sha: doc_id: 268540 cord_uid: wrjzr3ws file: cache/cord-271505-eot38721.json key: cord-271505-eot38721 authors: Wang, Hongliang; Rao, Shuan; Jiang, Chengyu title: Molecular pathogenesis of severe acute respiratory syndrome date: 2006-09-28 journal: Microbes Infect DOI: 10.1016/j.micinf.2006.06.012 sha: doc_id: 271505 cord_uid: eot38721 file: cache/cord-272603-nbosceoz.json key: cord-272603-nbosceoz authors: Lin, Qiuyuan; Wen, Donghua; Wu, Jing; Liu, Liling; Wu, Wenjuan; Fang, Xueen; Kong, Jilie title: Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min date: 2020-07-02 journal: Anal Chem DOI: 10.1021/acs.analchem.0c01635 sha: doc_id: 272603 cord_uid: nbosceoz file: cache/cord-272654-hh29olk7.json key: cord-272654-hh29olk7 authors: Bošnjak, Berislav; Stein, Saskia Catherina; Willenzon, Stefanie; Cordes, Anne Katrin; Puppe, Wolfram; Bernhardt, Günter; Ravens, Inga; Ritter, Christiane; Schultze-Florey, Christian R.; Gödecke, Nina; Martens, Jörg; Kleine-Weber, Hannah; Hoffmann, Markus; Cossmann, Anne; Yilmaz, Mustafa; Pink, Isabelle; Hoeper, Marius M.; Behrens, Georg M. 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P. title: The trinity of COVID-19: immunity, inflammation and intervention date: 2020-04-28 journal: Nat Rev Immunol DOI: 10.1038/s41577-020-0311-8 sha: doc_id: 274841 cord_uid: rcdoewwv file: cache/cord-275313-mfyff9ne.json key: cord-275313-mfyff9ne authors: Modjarrad, Kayvon title: Treatment strategies for Middle East respiratory syndrome coronavirus date: 2016-01-01 journal: Journal of virus eradication DOI: nan sha: doc_id: 275313 cord_uid: mfyff9ne file: cache/cord-274396-l611eisi.json key: cord-274396-l611eisi authors: Park, Su-Jin; Yu, Kwang-Min; Kim, Young-Il; Kim, Se-Mi; Kim, Eun-Ha; Kim, Seong-Gyu; Kim, Eun Ji; Casel, Mark Anthony B.; Rollon, Rare; Jang, Seung-Gyu; Lee, Min-Hyeok; Chang, Jae-Hyung; Song, Min-Suk; Jeong, Hye Won; Choi, Younho; Chen, Weiqiang; Shin, Woo-Jin; Jung, Jae U.; Choi, Young Ki title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 journal: mBio DOI: 10.1128/mbio.01114-20 sha: doc_id: 274396 cord_uid: l611eisi file: cache/cord-275252-4e3cn50u.json key: cord-275252-4e3cn50u authors: Rad SM, Ali Hosseini; McLellan, Alexander D. title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 journal: bioRxiv DOI: 10.1101/2020.05.15.098947 sha: doc_id: 275252 cord_uid: 4e3cn50u file: cache/cord-275926-rj23z7po.json key: cord-275926-rj23z7po authors: Fontanella, Marco M.; De Maria, Lucio; Zanin, Luca; Saraceno, Giorgio; Terzi di Bergamo, Lodovico; Servadei, Franco; Chaurasia, Bipin; Olivi, Alessandro; Vajkoczy, Peter; Schaller, Karl; Cappabianca, Paolo; Doglietto, Francesco title: Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey date: 2020-05-05 journal: World Neurosurg DOI: 10.1016/j.wneu.2020.04.204 sha: doc_id: 275926 cord_uid: rj23z7po file: cache/cord-275946-ofd2ipvs.json key: cord-275946-ofd2ipvs authors: Cheng, Matthew P.; Yansouni, Cedric P.; Basta, Nicole E.; Desjardins, Michaël; Kanjilal, Sanjat; Paquette, Katryn; Caya, Chelsea; Semret, Makeda; Quach, Caroline; Libman, Michael; Mazzola, Laura; Sacks, Jilian A.; Dittrich, Sabine; Papenburg, Jesse title: Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review date: 2020-06-04 journal: Ann Intern Med DOI: 10.7326/m20-2854 sha: doc_id: 275946 cord_uid: ofd2ipvs file: cache/cord-277841-7sp8ftbc.json key: cord-277841-7sp8ftbc authors: Kumari, Pratibha; Singh, Archana; Rinchui Ngasainao, Moses; Shakeel, Ilma; Kumar, Sanjay; Lal, Seema; Singhal, Anchal; Singh Sohal, Sukhwinder; Kumar Singh, Indrakant; Imtaiyaz Hassan, Md. title: Potential diagnostics and therapeutic approaches in COVID-19 date: 2020-08-12 journal: Clin Chim Acta DOI: 10.1016/j.cca.2020.08.013 sha: doc_id: 277841 cord_uid: 7sp8ftbc file: cache/cord-278522-e4qa19o6.json key: cord-278522-e4qa19o6 authors: Park, Se Yoon; Yun, Soon Gyu; Shin, Jeong Won; Lee, Bo Young; Son, Hyo-Ju; Lee, Seungjae; Lee, Eunjung; Kim, Tae Hyong title: Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs date: 2020-06-19 journal: Korean J Intern Med DOI: 10.3904/kjim.2020.203 sha: doc_id: 278522 cord_uid: e4qa19o6 file: cache/cord-275690-83nrzfon.json key: cord-275690-83nrzfon authors: Stanifer, Megan L.; Kee, Carmon; Cortese, Mirko; Triana, Sergio; Mukenhirn, Markus; Kraeusslich, Hans-Georg; Alexandrov, Theodore; Bartenschlager, Ralf; Boulant, Steeve title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 journal: bioRxiv DOI: 10.1101/2020.04.24.059667 sha: doc_id: 275690 cord_uid: 83nrzfon file: cache/cord-277487-jgbjxgh1.json key: cord-277487-jgbjxgh1 authors: Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij-Rammerstorfer, Sandra; Wright, Daniel; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W. P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valerie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.20.159715 sha: doc_id: 277487 cord_uid: jgbjxgh1 file: cache/cord-278362-pwi48i20.json key: cord-278362-pwi48i20 authors: Khan, Abbas; Ali, Syed Shujait; Khan, Muhammad Tahir; Saleem, Shoaib; Ali, Arif; Suleman, Muhammad; Babar, Zainib; Shafiq, Athar; Khan, Mazhar; Wei, Dong-Qing title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) date: 2020-06-18 journal: J Biomol Struct Dyn DOI: 10.1080/07391102.2020.1779128 sha: doc_id: 278362 cord_uid: pwi48i20 file: cache/cord-279443-2e4gz2bo.json key: cord-279443-2e4gz2bo authors: Khan, Suliman; Liu, Jianbo; Xue, Mengzhou title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns date: 2020-06-09 journal: Front Med (Lausanne) DOI: 10.3389/fmed.2020.00310 sha: doc_id: 279443 cord_uid: 2e4gz2bo file: cache/cord-274802-7ioiwsd8.json key: cord-274802-7ioiwsd8 authors: Varghese, Praveen Mathews; Tsolaki, Anthony G.; Yasmin, Hadida; Shastri, Abhishek; Ferluga, Janez; Vatish, Manu; Madan, Taruna; Kishore, Uday title: Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies date: 2020-08-19 journal: Immunobiology DOI: 10.1016/j.imbio.2020.152008 sha: doc_id: 274802 cord_uid: 7ioiwsd8 file: cache/cord-276630-qci7khki.json key: cord-276630-qci7khki authors: Lima, William Gustavo; Brito, Júlio César Moreira; Overhage, Joerg; Nizer, Waleska Stephanie da Cruz title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review date: 2020-06-08 journal: Arch Virol DOI: 10.1007/s00705-020-04693-5 sha: doc_id: 276630 cord_uid: qci7khki file: cache/cord-277253-vy0mvzeb.json key: cord-277253-vy0mvzeb authors: Liu, Hongbo; Ye, Fei; Sun, Qi; Liang, Hao; Li, Chunmei; Lu, Roujian; Huang, Baoying; Tan, Wenjie; Lai, Luhua title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.10.035824 sha: doc_id: 277253 cord_uid: vy0mvzeb file: cache/cord-278370-fuu20ae7.json key: cord-278370-fuu20ae7 authors: Palao, M.; Fernández-Díaz, E.; Gracia-Gil, J.; Romero-Sánchez, C.M.; Díaz-Maroto, I.; Segura, T. title: Multiple Sclerosis following SARS-CoV-2 infection date: 2020-07-07 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2020.102377 sha: doc_id: 278370 cord_uid: fuu20ae7 file: cache/cord-280662-gakayv6e.json key: cord-280662-gakayv6e authors: Bian, Jingwei; Li, Zijian title: Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator date: 2020-10-13 journal: Acta Pharm Sin B DOI: 10.1016/j.apsb.2020.10.006 sha: doc_id: 280662 cord_uid: gakayv6e file: cache/cord-277399-0w8is9xm.json key: cord-277399-0w8is9xm authors: Esteves, Sandro C.; Lombardo, Francesco; Garrido, Nicolás; Alvarez, Juan; Zini, Armand; Colpi, Giovanni M.; Kirkman‐Brown, Jackson; Lewis, Sheena E. M.; Björndahl, Lars; Majzoub, Ahmad; Cho, Chak‐Lam; Vendeira, Pedro; Hallak, Jorge; Amar, Edouard; Cocuzza, Marcello; Bento, Fabiola C.; Figueira, Rita C.; Sciorio, Romualdo; Laursen, Rita J.; Metwalley, Ahmad M.; Jindal, Sunil K.; Parekattil, Sijo; Ramasamy, Ranjith; Alviggi, Carlo; Humaidan, Peter; Yovich, John L.; Agarwal, Ashok title: SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services date: 2020-05-22 journal: Andrology DOI: 10.1111/andr.12809 sha: doc_id: 277399 cord_uid: 0w8is9xm file: cache/cord-278618-7tu5c7m1.json key: cord-278618-7tu5c7m1 authors: Romano-Bertrand, Sara; Aho-Glele, Ludwig-Serge; Grandbastien, Bruno; Gehanno, Jean-François; Lepelletier, Didier title: Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission? date: 2020-06-12 journal: J Hosp Infect DOI: 10.1016/j.jhin.2020.06.018 sha: doc_id: 278618 cord_uid: 7tu5c7m1 file: cache/cord-280068-rszu1c48.json key: cord-280068-rszu1c48 authors: Twomey, Julianne D.; Luo, Shen; Dean, Alexis Q.; Bozza, William P.; Nalli, Ancy; Zhang, Baolin title: COVID-19 update: The race to therapeutic development date: 2020-10-24 journal: Drug Resist Updat DOI: 10.1016/j.drup.2020.100733 sha: doc_id: 280068 cord_uid: rszu1c48 file: cache/cord-281281-knelqmzx.json key: cord-281281-knelqmzx authors: Villas-Boas, Gustavo R.; Rescia, Vanessa C.; Paes, Marina M.; Lavorato, Stefânia N.; de Magalhães-Filho, Manoel F.; Cunha, Mila S.; Simões, Rafael da C.; de Lacerda, Roseli B.; de Freitas-Júnior, Renilson S.; Ramos, Bruno H. da S.; Mapeli, Ana M.; Henriques, Matheus da S. T.; de Freitas, William R.; Lopes, Luiz A. F.; Oliveira, Luiz G. R.; da Silva, Jonatas G.; Silva-Filho, Saulo E.; da Silveira, Ana P. S.; Leão, Katyuscya V.; Matos, Maria M. de S.; Fernandes, Jamille S.; Cuman, Roberto K. N.; Silva-Comar, Francielli M. de S.; Comar, Jurandir F.; Brasileiro, Luana do A.; dos Santos, Jussileide N.; Oesterreich, Silvia A. title: The New Coronavirus (SARS-CoV-2): A Comprehensive Review on Immunity and the Application of Bioinformatics and Molecular Modeling to the Discovery of Potential Anti-SARS-CoV-2 Agents date: 2020-09-07 journal: Molecules DOI: 10.3390/molecules25184086 sha: doc_id: 281281 cord_uid: knelqmzx file: cache/cord-281529-2rec51xg.json key: cord-281529-2rec51xg authors: Haagmans, Bart L; Al Dhahiry, Said H S; Reusken, Chantal B E M; Raj, V Stalin; Galiano, Monica; Myers, Richard; Godeke, Gert-Jan; Jonges, Marcel; Farag, Elmoubasher; Diab, Ayman; Ghobashy, Hazem; Alhajri, Farhoud; Al-Thani, Mohamed; Al-Marri, Salih A; Al Romaihi, Hamad E; Al Khal, Abdullatif; Bermingham, Alison; Osterhaus, Albert D M E; AlHajri, Mohd M; Koopmans, Marion P G title: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation date: 2013-12-17 journal: Lancet Infect Dis DOI: 10.1016/s1473-3099(13)70690-x sha: doc_id: 281529 cord_uid: 2rec51xg file: cache/cord-277076-yvsyo4l9.json key: cord-277076-yvsyo4l9 authors: Berger, A.; Preiser, W. title: SARS date: 2019-09-12 journal: Encyclopedia of Environmental Health DOI: 10.1016/b978-0-444-63951-6.00624-0 sha: doc_id: 277076 cord_uid: yvsyo4l9 file: cache/cord-282142-76jr4p7n.json key: cord-282142-76jr4p7n authors: Wang, Yun; Wang, Yiliang; Han, Xiaoxue; Ye, Jiazhuo; Li, Ruiman title: Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS date: 2020-08-07 journal: Front Pediatr DOI: 10.3389/fped.2020.00511 sha: doc_id: 282142 cord_uid: 76jr4p7n file: cache/cord-280774-r2xm164s.json key: cord-280774-r2xm164s authors: Gallizzi, Romina; Sutera, Diana; Spagnolo, Alessandra; Bagnato, Anna Maria; Cannavò, Serafinella Patrizia; Grasso, Loredana; Guarneri, Claudio; Nunnari, Giuseppe; Mazza, Francesca; Pajno, Giovanni Battista title: Management of pernio‐like cutaneous manifestations in children during the outbreak of covid‐19. date: 2020-09-19 journal: Dermatol Ther DOI: 10.1111/dth.14312 sha: doc_id: 280774 cord_uid: r2xm164s file: cache/cord-279940-i2rgjpxf.json key: cord-279940-i2rgjpxf authors: Comentale, Giuseppe; Manzo, Rachele; Pilato, Emanuele title: Sars-Cov-2 interference in HEME production: is it the time for an early predictive biomarker? date: 2020-06-29 journal: J Mol Med (Berl) DOI: 10.1007/s00109-020-01945-4 sha: doc_id: 279940 cord_uid: i2rgjpxf file: cache/cord-282338-u01qv3uc.json key: cord-282338-u01qv3uc authors: Cherry, James. D. title: The chronology of the 2002–2003 SARS mini pandemic date: 2004-11-05 journal: Paediatr Respir Rev DOI: 10.1016/j.prrv.2004.07.009 sha: doc_id: 282338 cord_uid: u01qv3uc file: cache/cord-279105-e2zjxjox.json key: cord-279105-e2zjxjox authors: Lee, Cheryl Yi-Pin; Lin, Raymond T. P.; Renia, Laurent; Ng, Lisa F. P. title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 journal: Front Immunol DOI: 10.3389/fimmu.2020.00879 sha: doc_id: 279105 cord_uid: e2zjxjox file: cache/cord-283956-zgrtux7i.json key: cord-283956-zgrtux7i authors: Amin, Sk. 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R.; Richt, Juergen A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.08.15.252395 sha: doc_id: 281679 cord_uid: xmbnpawj file: cache/cord-281684-m3m4mhye.json key: cord-281684-m3m4mhye authors: Fagre, Anna C.; Manhard, John; Adams, Rachel; Eckley, Miles; Zhan, Shijun; Lewis, Juliette; Rocha, Savannah M.; Woods, Catherine; Kuo, Karina; Liao, Wuxiang; Li, Lin; Corper, Adam; Challa, Dilip; Mount, Emily; Tumanut, Christine; Tjalkens, Ronald B.; Aboelleil, Tawfik; Fan, Xiaomin; Schountz, Tony title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 journal: bioRxiv DOI: 10.1101/2020.09.25.313601 sha: doc_id: 281684 cord_uid: m3m4mhye file: cache/cord-279255-v861kk0i.json key: cord-279255-v861kk0i authors: Dhama, Kuldeep; Khan, Sharun; Tiwari, Ruchi; Sircar, Shubhankar; Bhat, Sudipta; Malik, Yashpal Singh; Singh, Karam Pal; Chaicumpa, Wanpen; Bonilla-Aldana, D. Katterine; Rodriguez-Morales, Alfonso J. title: Coronavirus Disease 2019–COVID-19 date: 2020-06-24 journal: Clin Microbiol Rev DOI: 10.1128/cmr.00028-20 sha: doc_id: 279255 cord_uid: v861kk0i file: cache/cord-284867-p4jgyusp.json key: cord-284867-p4jgyusp authors: Schöler, Lara; Le-Trilling, Vu Thuy Khanh; Eilbrecht, Mareike; Mennerich, Denise; Anastasiou, Olympia E.; Krawczyk, Adalbert; Herrmann, Anke; Dittmer, Ulf; Trilling, Mirko title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 journal: Front Immunol DOI: 10.3389/fimmu.2020.573526 sha: doc_id: 284867 cord_uid: p4jgyusp file: cache/cord-282058-it0ojdk3.json key: cord-282058-it0ojdk3 authors: Yu, Yuanqiang; Chen, Pingyang title: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review date: 2020-05-15 journal: Front Pediatr DOI: 10.3389/fped.2020.00287 sha: doc_id: 282058 cord_uid: it0ojdk3 file: cache/cord-287501-7it4kh0e.json key: cord-287501-7it4kh0e authors: Roh, Changhyun title: A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide date: 2012-05-03 journal: Int J Nanomedicine DOI: 10.2147/ijn.s31379 sha: doc_id: 287501 cord_uid: 7it4kh0e file: cache/cord-280821-kc0ut4oy.json key: cord-280821-kc0ut4oy authors: Venturini, Elisabetta; Montagnani, Carlotta; Garazzino, Silvia; Donà, Daniele; Pierantoni, Luca; Lo Vecchio, Andrea; Nicolini, Giangiacomo; Bianchini, Sonia; Krzysztofiak, Andrzej; Galli, Luisa; Villani, Alberto; Castelli-Gattinara, Guido title: Treatment of children with COVID-19: position paper of the Italian Society of Pediatric Infectious Disease date: 2020-09-24 journal: Ital J Pediatr DOI: 10.1186/s13052-020-00900-w sha: doc_id: 280821 cord_uid: kc0ut4oy file: cache/cord-284498-54j6ys8s.json key: cord-284498-54j6ys8s authors: Ihsanullah, Ihsanullah; Bilal, Muhammad; Naushad, Mu. title: Coronavirus 2 (SARS-CoV-2) in water environments: Current status, challenges and research opportunities date: 2020-10-16 journal: nan DOI: 10.1016/j.jwpe.2020.101735 sha: doc_id: 284498 cord_uid: 54j6ys8s file: cache/cord-284068-sbon3aes.json key: cord-284068-sbon3aes authors: Mok, Chee Keng; Ng, Yan Ling; Ahidjo, Bintou Ahmadou; Hua Lee, Regina Ching; Choy Loe, Marcus Wing; Liu, Jing; Tan, Kai Sen; Kaur, Parveen; Chng, Wee Joo; Wong, John Eu-Li; Wang, De Yun; Hao, Erwei; Hou, Xiaotao; Tan, Yong Wah; Mak, Tze Minn; Lin, Cui; Lin, Raymond; Tambyah, Paul; Deng, JiaGang; Hann Chu, Justin Jang title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 journal: bioRxiv DOI: 10.1101/2020.06.21.162396 sha: doc_id: 284068 cord_uid: sbon3aes file: cache/cord-284589-j1609xlu.json key: cord-284589-j1609xlu authors: Sedova, Mayya; Jaroszewski, Lukasz; Alisoltani, Arghavan; Godzik, Adam title: Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence date: 2020-05-29 journal: Bioinformatics DOI: 10.1093/bioinformatics/btaa550 sha: doc_id: 284589 cord_uid: j1609xlu file: cache/cord-285168-qkadqohe.json key: cord-285168-qkadqohe authors: Delatorre, Edson; Mir, Daiana; Graf, Tiago; Bello, Gonzalo title: Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries date: 2020-04-23 journal: nan DOI: 10.1101/2020.04.20.20073007 sha: doc_id: 285168 cord_uid: qkadqohe file: cache/cord-287658-c2lljdi7.json key: cord-287658-c2lljdi7 authors: Lopez-Rincon, Alejandro; Tonda, Alberto; Mendoza-Maldonado, Lucero; Mulders, Daphne G.J.C.; Molenkamp, Richard; Perez-Romero, Carmina A.; Claassen, Eric; Garssen, Johan; Kraneveld, Aletta D. title: Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date: 2020-09-10 journal: bioRxiv DOI: 10.1101/2020.03.13.990242 sha: doc_id: 287658 cord_uid: c2lljdi7 file: cache/cord-286298-pn9nwl64.json key: cord-286298-pn9nwl64 authors: Helmy, Yosra A.; Fawzy, Mohamed; Elaswad, Ahmed; Sobieh, Ahmed; Kenney, Scott P.; Shehata, Awad A. title: The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control date: 2020-04-24 journal: J Clin Med DOI: 10.3390/jcm9041225 sha: doc_id: 286298 cord_uid: pn9nwl64 file: cache/cord-288731-x2cwyvb7.json key: cord-288731-x2cwyvb7 authors: Puenpa, Jiratchaya; Suwannakarn, Kamol; Chansaenroj, Jira; Nilyanimit, Pornjarim; Yorsaeng, Ritthideach; Auphimai, Chompoonut; Kitphati, Rungrueng; Mungaomklang, Anek; Kongklieng, Amornmas; Chirathaworn, Chintana; Wanlapakorn, Nasamon; Poovorawan, Yong title: Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date: 2020-10-06 journal: Sci Rep DOI: 10.1038/s41598-020-73554-7 sha: doc_id: 288731 cord_uid: x2cwyvb7 file: cache/cord-289716-nleql08z.json key: cord-289716-nleql08z authors: Tsitsilonis, Ourania E.; Paraskevis, Dimitrios; Lianidou, Evi; Pierros, Vassilios; Akalestos, Athanasios; Kastritis, Efstathios; Moutsatsou, Paraskevi; Scorilas, Andreas; Sphicopoulos, Thomas; Terpos, Evangelos; Thomaidis, Nikolaos; Tsakris, Athanassios; Voulgaris, Nikolaos; Daskalaki, Christina C.; Evangelakou, Zoi; Fouki, Christina; Gianniou, Despoina D.; Gumeni, Sentiljana; Kostaki, Evangelia-Georgia; Kostopoulos, Ioannis V.; Manola, Maria S.; Orologas-Stavrou, Nikolaos; Panteli, Chrysanthi; Papanagnou, Eleni-Dimitra; Rousakis, Pantelis; Sklirou, Aimilia D.; Smilkou, Stavroula; Stergiopoulou, Dimitra; Trougakos, Ioannis P.; Tsiodras, Soritios; Sfikakis, Petros P.; Dimopoulos, Meletios-Athanasios title: Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report date: 2020-09-21 journal: Life (Basel) DOI: 10.3390/life10090214 sha: doc_id: 289716 cord_uid: nleql08z file: cache/cord-289588-n61gz7pi.json key: cord-289588-n61gz7pi authors: Samudrala, Pavan Kumar; Kumar, Pramod; Choudhary, Kamlesh; Thakur, Nagender; Wadekar, Gaurav Suresh; Dayaramani, Richa; Agrawal, Mukta; Alexander, Amit title: Virology, pathogenesis, diagnosis and in-line treatment of COVID-19 date: 2020-07-17 journal: Eur J Pharmacol DOI: 10.1016/j.ejphar.2020.173375 sha: doc_id: 289588 cord_uid: n61gz7pi file: cache/cord-286269-vrjyj2y1.json key: cord-286269-vrjyj2y1 authors: Sagheb, Setareh; Lamsehchi, Ameneh; Jafary, Mohamadreza; Atef-Yekta, Reza; Sadeghi, Kourosh title: Two seriously ill neonates born to mothers with COVID-19 pneumonia- a case report date: 2020-09-21 journal: Ital J Pediatr DOI: 10.1186/s13052-020-00897-2 sha: doc_id: 286269 cord_uid: vrjyj2y1 file: cache/cord-290056-x74cq2k5.json key: cord-290056-x74cq2k5 authors: Delgado-Roche, Livan; Mesta, Fernando title: Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection date: 2020-04-30 journal: Arch Med Res DOI: 10.1016/j.arcmed.2020.04.019 sha: doc_id: 290056 cord_uid: x74cq2k5 file: cache/cord-289407-8fje16z1.json key: cord-289407-8fje16z1 authors: Moore, G.; Rickard, H.; Stevenson, D.; Aranega Bou, P.; Pitman, J.; Crook, A.; Davies, K.; Spencer, A.; Burton, C.; Easterbrook, L.; Love, H. E.; Summers, S.; Welch, S. R.; Wand, N.; Thompson, K.-A.; Pottage, T.; Richards, K. S.; Dunning, J.; Bennett, A. title: Detection of SARS-CoV-2 within the healthcare environment: a multicentre study conducted during the first wave of the COVID-19 outbreak in England date: 2020-09-25 journal: nan DOI: 10.1101/2020.09.24.20191411 sha: doc_id: 289407 cord_uid: 8fje16z1 file: cache/cord-290792-ggcz1zfw.json key: cord-290792-ggcz1zfw authors: Qutob, N.; Awartani, F.; Salah, Z.; Asia, M.; Abu Khader, I.; Herzallah, K.; Balqis, N.; Sallam, H. title: Seroprevalence of SARS-CoV-2 in Palestine: a cross-sectional seroepidemiological study date: 2020-09-01 journal: nan DOI: 10.1101/2020.08.28.20180083 sha: doc_id: 290792 cord_uid: ggcz1zfw file: cache/cord-290796-x9xqqcj6.json key: cord-290796-x9xqqcj6 authors: Stefanelli, P.; Bella, A.; Fedele, G.; Fiore, S.; Pancheri, S.; Benedetti, E.; Fabiani, C.; Leone, P.; Vacca, P.; Schiavoni, I.; Neri, A.; Carannante, A.; Simmaco, M.; Santino, I.; Zuccali, M. G.; Bizzarri, G.; Magnoni, R.; Benetollo, P. P.; Brusaferro, S.; Rezza, G.; Ferro, A. title: Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento date: 2020-11-13 journal: nan DOI: 10.1101/2020.11.11.20229062 sha: doc_id: 290796 cord_uid: x9xqqcj6 file: cache/cord-289535-srrfr1es.json key: cord-289535-srrfr1es authors: Tregoning, J. S.; Brown, E. S.; Cheeseman, H. M.; Flight, K. E.; Higham, S. L.; Lemm, N.‐M.; Pierce, B. F.; Stirling, D. C.; Wang, Z.; Pollock, K. M. title: Vaccines for COVID‐19 date: 2020-10-18 journal: Clin Exp Immunol DOI: 10.1111/cei.13517 sha: doc_id: 289535 cord_uid: srrfr1es file: cache/cord-290290-wyx9ib7s.json key: cord-290290-wyx9ib7s authors: Sinegubova, Maria V.; Orlova, Nadezhda A.; Kovnir, Sergey V.; Dayanova, Lutsia K.; Vorobiev, Ivan I title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.368092 sha: doc_id: 290290 cord_uid: wyx9ib7s file: cache/cord-293688-g6kag5ij.json key: cord-293688-g6kag5ij authors: Nora, Holtmann; Philippos, Edimiris; Marcel, Andree; Cornelius, Doehmen; Dunja, Baston-Buest; Ortwin, Adams; Jan-Steffen, Kruessel; Petra, Bielfeld Alexandra title: Assessment of SARS-CoV-2 in human semen - a cohort study date: 2020-05-29 journal: Fertil Steril DOI: 10.1016/j.fertnstert.2020.05.028 sha: doc_id: 293688 cord_uid: g6kag5ij file: cache/cord-288484-qy619tfg.json key: cord-288484-qy619tfg authors: Bernard‐Valnet, R.; Pizzarotti, B.; Anichini, A.; Demars, Y.; Russo, E.; Schmidhauser, M.; Cerutti‐Sola, J.; Rossetti, A. O.; Du Pasquier, R. title: Two patients with acute meningoencephalitis concomitant with SARS‐CoV‐2 infection date: 2020-05-30 journal: Eur J Neurol DOI: 10.1111/ene.14298 sha: doc_id: 288484 cord_uid: qy619tfg file: cache/cord-292025-dr611nse.json key: cord-292025-dr611nse authors: Kam, Kai-qian; Yung, Chee Fu; Maiwald, Matthias; Chong, Chia Yin; Soong, Han Yang; Loo, Liat Hui; Tan, Natalie Woon Hui; Li, Jiahui; Nadua, Karen Donceras; Thoon, Koh Cheng title: Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children date: 2020-06-13 journal: J Pediatric Infect Dis Soc DOI: 10.1093/jpids/piaa068 sha: doc_id: 292025 cord_uid: dr611nse file: cache/cord-287847-rmhvc5n5.json key: cord-287847-rmhvc5n5 authors: Miles, Brett A.; Schiff, Bradley; Ganly, Ian; Ow, Thomas; Cohen, Erik; Genden, Eric; Culliney, Bruce; Mehrotra, Bhoomi; Savona, Steven; Wong, Richard J.; Haigentz, Missak; Caruana, Salvatore; Givi, Babak; Patel, Kepal; Hu, Kenneth title: Tracheostomy during SARS‐CoV‐2 pandemic: Recommendations from the New York Head and Neck Society date: 2020-04-20 journal: Head Neck DOI: 10.1002/hed.26166 sha: doc_id: 287847 cord_uid: rmhvc5n5 file: cache/cord-291523-4dtk1kyh.json key: cord-291523-4dtk1kyh authors: Nguyen, Thanh Thi; Abdelrazek, Mohamed; Nguyen, Dung Tien; Aryal, Sunil; Nguyen, Duc Thanh; Khatami, Amin title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.05.12.091397 sha: doc_id: 291523 cord_uid: 4dtk1kyh file: cache/cord-292742-mio4przi.json key: cord-292742-mio4przi authors: McAloose, Denise; Laverack, Melissa; Wang, Leyi; Killian, Mary Lea; Caserta, Leonardo C.; Yuan, Fangfeng; Mitchell, Patrick K.; Queen, Krista; Mauldin, Matthew R.; Cronk, Brittany D.; Bartlett, Susan L.; Sykes, John M.; Zec, Stephanie; Stokol, Tracy; Ingerman, Karen; Delaney, Martha A.; Fredrickson, Richard; Ivančić, Marina; Jenkins-Moore, Melinda; Mozingo, Katie; Franzen, Kerrie; Bergeson, Nichole Hines; Goodman, Laura; Wang, Haibin; Fang, Ying; Olmstead, Colleen; McCann, Colleen; Thomas, Patrick; Goodrich, Erin; Elvinger, François; Smith, David C.; Tong, Suxiang; Slavinski, Sally; Calle, Paul P.; Terio, Karen; Torchetti, Mia Kim; Diel, Diego G. title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 journal: mBio DOI: 10.1128/mbio.02220-20 sha: doc_id: 292742 cord_uid: mio4przi file: cache/cord-293082-fw7deem8.json key: cord-293082-fw7deem8 authors: Zhang, Guangzhi; Li, Bin; Yoo, Dongwan; Qin, Tong; Zhang, Xiaodon; Jia, Yaxiong; Cui, Shangjin title: Animal coronaviruses and SARS‐CoV‐2 date: 2020-08-16 journal: Transbound Emerg Dis DOI: 10.1111/tbed.13791 sha: doc_id: 293082 cord_uid: fw7deem8 file: cache/cord-286683-mettlmhz.json key: cord-286683-mettlmhz authors: Ortiz-Prado, Esteban; Simbaña-Rivera, Katherine; Gómez-Barreno, Lenin; Rubio-Neira, Mario; Guaman, Linda P.; Kyriakidis, Nikolaos C; Muslin, Claire; Jaramillo, Ana María Gómez; Barba-Ostria, Carlos; Cevallos-Robalino, Doménica; Sanches-SanMiguel, Hugo; Unigarro, Luis; Zalakeviciute, Rasa; Gadian, Naomi; López-Cortés, Andrés title: Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review date: 2020-05-30 journal: Diagn Microbiol Infect Dis DOI: 10.1016/j.diagmicrobio.2020.115094 sha: doc_id: 286683 cord_uid: mettlmhz file: cache/cord-291397-look6ddt.json key: cord-291397-look6ddt authors: Roberto, Palumbo; Francesco, Londrino; Emanuela, Cordova; Giorgia, Gambardella; Pasquale, Niscola; Sara, Dominijanni title: Current treatment of COVID-19 in renal patients: hope or hype? date: 2020-09-28 journal: Intern Emerg Med DOI: 10.1007/s11739-020-02510-0 sha: doc_id: 291397 cord_uid: look6ddt file: cache/cord-289598-t8upoq9a.json key: cord-289598-t8upoq9a authors: Yoon, Jane C; Montgomery, Martha P; Buff, Ann M; Boyd, Andrew T; Jamison, Calla; Hernandez, Alfonso; Schmit, Kristine; Shah, Sarita; Ajoku, Sophia; Holland, David P; Prieto, Juliana; Smith, Sasha; Swancutt, Mark A; Turner, Kim; Andrews, Tom; Flowers, Kevin; Wells, Alyssa; Marchman, Cathryn; Laney, Emaline; Bixler, Danae; Cavanaugh, Sean; Flowers, Nicole; Gaffga, Nicholas; Ko, Jean Y; Paulin, Heather N; Weng, Mark K; Mosites, Emily; Morris, Sapna Bamrah title: COVID-19 Prevalence among People Experiencing Homelessness and Homelessness Service Staff during Early Community Transmission in Atlanta, Georgia, April–May 2020 date: 2020-09-08 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa1340 sha: doc_id: 289598 cord_uid: t8upoq9a file: cache/cord-293274-ysr1l557.json key: cord-293274-ysr1l557 authors: Perisé-Barrios, Ana Judith; Tomeo-Martín, Beatriz Davinia; Gómez-Ochoa, Pablo; Delgado-Bonet, Pablo; Plaza, Pedro; Palau-Concejo, Paula; González, Jorge; Ortiz-Diez, Gustavo; Meléndez-Lazo, Antonio; Gentil, Michaela; García-Castro, Javier; Barbero-Fernández, Alicia title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.09.22.308023 sha: doc_id: 293274 cord_uid: ysr1l557 file: cache/cord-287758-da11ypiy.json key: cord-287758-da11ypiy authors: Mônica Vitalino de Almeida, Sinara; Cleberson Santos Soares, José; Lima dos Santos, Keriolaine; Emanuel Ferreira Alves, Josival; Galdino Ribeiro, Amélia; Trindade Tenório Jacob, Íris; Juliane da Silva Ferreira, Cindy; Celerino dos Santos, Jéssica; Ferreira de Oliveira, Jamerson; Bezerra de Carvalho Junior, Luiz; do Carmo Alves de Lima, Maria title: COVID-19 therapy: what weapons do we bring into battle? date: 2020-09-10 journal: Bioorg Med Chem DOI: 10.1016/j.bmc.2020.115757 sha: doc_id: 287758 cord_uid: da11ypiy file: cache/cord-290904-ngvhk0qy.json key: cord-290904-ngvhk0qy authors: Zheng, Zhiqiang; Monteil, Vanessa Marthe; Maurer-Stroh, Sebastian; Yew, Chow Wenn; Leong, Carol; Mohd-Ismail, Nur Khairiah; Cheyyatraivendran Arularasu, Suganya; Chow, Vincent Tak Kwong; Lin, Raymond Tzer Pin; Mirazimi, Ali; Hong, Wanjin; Tan, Yee-Joo title: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date: 2020-07-16 journal: Euro Surveill DOI: 10.2807/1560-7917.es.2020.25.28.2000291 sha: doc_id: 290904 cord_uid: ngvhk0qy file: cache/cord-292152-gmru83ac.json key: cord-292152-gmru83ac authors: Makrinioti, Heidi; Mac Donald, Alexander; Lu, X; Wallace, S; Mathew, Jobson; Zhang, F; Shao, J; Bretherton, J; Tariq, Mehmood; Eyre, E; Wong, A; Pakkiri, L; Saxena, Amulya K; Wong, G W title: Intussusception in two children with SARS-CoV-2 infection in children date: 2020-08-08 journal: J Pediatric Infect Dis Soc DOI: 10.1093/jpids/piaa096 sha: doc_id: 292152 cord_uid: gmru83ac file: cache/cord-292256-jp80u828.json key: cord-292256-jp80u828 authors: Moriguchi, Takeshi; Harii, Norikazu; Goto, Junko; Harada, Daiki; Sugawara, Hisanori; Takamino, Junichi; Ueno, Masateru; Sakata, Hiroki; Kondo, Kengo; Myose, Natsuhiko; Nakao, Atsuhito; Takeda, Masayuki; Haro, Hirotaka; Inoue, Osamu; Suzuki-Inoue, Katsue; Kubokawa, Kayo; Ogihara, Shinji; Sasaki, Tomoyuki; Kinouchi, Hiroyuki; Kojin, Hiroyuki; Ito, Masami; Onishi, Hiroshi; Shimizu, Tatsuya; Sasaki, Yu; Enomoto, Nobuyuki; Ishihara, Hiroshi; Furuya, Shiomi; Yamamoto, Tomoko; Shimada, Shinji title: A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 date: 2020-04-03 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.03.062 sha: doc_id: 292256 cord_uid: jp80u828 file: cache/cord-291436-cu5o8ipw.json key: cord-291436-cu5o8ipw authors: Martínez-Hernández, Fernando; Isaak-Delgado, Ana Belem; Alfonso-Toledo, Jorge Alberto; Muñoz-García, Claudia Irais; Villalobos, Guiehdani; Aréchiga-Ceballos, Nidia; Rendón-Franco, Emilio title: Assessing the SARS-CoV-2 threat to wildlife: Potential risk to a broad range of mammals date: 2020-10-05 journal: Perspect Ecol Conserv DOI: 10.1016/j.pecon.2020.09.008 sha: doc_id: 291436 cord_uid: cu5o8ipw file: cache/cord-293578-yu2i0u2h.json key: cord-293578-yu2i0u2h authors: Kusadasi, Nuray; Sikma, Maaike; Huisman, Albert; Westerink, Jan; Maas, Coen; Schutgens, Roger title: A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy date: 2020-08-10 journal: Hemasphere DOI: 10.1097/hs9.0000000000000457 sha: doc_id: 293578 cord_uid: yu2i0u2h file: cache/cord-293691-ewerquin.json key: cord-293691-ewerquin authors: Sauerhering, Lucie; Kupke, Alexandra; Meier, Lars; Dietzel, Erik; Hoppe, Judith; Gruber, Achim D.; Gattenloehner, Stefan; Witte, Biruta; Fink, Ludger; Hofmann, Nina; Zimmermann, Tobias; Goesmann, Alexander; Nist, Andrea; Stiewe, Thorsten; Becker, Stephan; Herold, Susanne; Peteranderl, Christin title: Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice date: 2020-07-02 journal: Eur Respir J DOI: 10.1183/13993003.01826-2019 sha: doc_id: 293691 cord_uid: ewerquin file: cache/cord-291710-ixun0c8g.json key: cord-291710-ixun0c8g authors: Su, Haixia; Yao, Sheng; Zhao, Wenfeng; Li, Minjun; Liu, Jia; Shang, WeiJuan; Xie, Hang; Ke, Changqiang; Gao, Meina; Yu, Kunqian; Liu, Hong; Shen, Jingshan; Tang, Wei; Zhang, Leike; Zuo, Jianping; Jiang, Hualiang; Bai, Fang; Wu, Yan; Ye, Yang; Xu, Yechun title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.13.038687 sha: doc_id: 291710 cord_uid: ixun0c8g file: cache/cord-291916-5yqc3zcx.json key: cord-291916-5yqc3zcx authors: Hozhabri, Hossein; Piceci Sparascio, Francesca; Sohrabi, Hamidreza; Mousavifar, Leila; Roy, René; Scribano, Daniela; De Luca, Alessandro; Ambrosi, Cecilia; Sarshar, Meysam title: The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting date: 2020-08-05 journal: Int J Environ Res Public Health DOI: 10.3390/ijerph17165648 sha: doc_id: 291916 cord_uid: 5yqc3zcx file: cache/cord-293056-kz3w0nfh.json key: cord-293056-kz3w0nfh authors: Indes, Jeffrey E.; Koleilat, Issam; Hatch, Ayesha Nzeribe; Choinski, Krystina; Jones, Davis Brent; Aldailami, Hasan; Billett, Henny; Denesopolis, John M.; Lipsitz, Evan title: Early Experience with Arterial Thromboembolic Complications in Patents with COVID-19 date: 2020-08-28 journal: J Vasc Surg DOI: 10.1016/j.jvs.2020.07.089 sha: doc_id: 293056 cord_uid: kz3w0nfh file: cache/cord-296237-i9cti2ok.json key: cord-296237-i9cti2ok authors: Díez, José-María; Romero, Carolina; Vergara-Alert, Júlia; Belló-Perez, Melissa; Rodon, Jordi; Honrubia, José Manuel; Segalés, Joaquim; Sola, Isabel; Enjuanes, Luis; Gajardo, Rodrigo title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.160879 sha: doc_id: 296237 cord_uid: i9cti2ok file: cache/cord-293988-f5gvwjyh.json key: cord-293988-f5gvwjyh authors: Musso, Nicolò; Costantino, Angelita; La Spina, Sebastiano; Finocchiaro, Alessandra; Andronico, Francesca; Stracquadanio, Stefano; Liotta, Luigi; Visalli, Rosanna; Emmanuele, Giovanni title: New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab date: 2020-09-11 journal: Pathogens DOI: 10.3390/pathogens9090746 sha: doc_id: 293988 cord_uid: f5gvwjyh file: cache/cord-294069-7zr77r71.json key: cord-294069-7zr77r71 authors: Hu, Xiaowen; Ni, Wei; Wang, Zhaoguo; Ma, Guangren; Pan, Bei; Dong, Liyan; Gao, Ruqin; Jiang, Fachun title: The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients date: 2020-09-30 journal: Ecotoxicol Environ Saf DOI: 10.1016/j.ecoenv.2020.111438 sha: doc_id: 294069 cord_uid: 7zr77r71 file: cache/cord-293890-thfros7x.json key: cord-293890-thfros7x authors: Carbo, Ellen C.; Sidorov, Igor A.; Zevenhoven-Dobbe, Jessica C.; Snijder, Eric J.; Claas, Eric C.; Laros, Jeroen F.J.; Kroes, Aloys C.M.; de Vries, Jutte J.C. title: Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness date: 2020-08-21 journal: J Clin Virol DOI: 10.1016/j.jcv.2020.104594 sha: doc_id: 293890 cord_uid: thfros7x file: cache/cord-296219-zzg9hds0.json key: cord-296219-zzg9hds0 authors: Battaglini, Denise; 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Cento, Valeria; Antonello, Maria; Colagrossi, Luna; Merli, Marco; Ughi, Nicola; Renica, Silvia; Matarazzo, Elisa; Di Ruscio, Federica; Tartaglione, Livia; Colombo, Jacopo; Grimaldi, Chiara; Carta, Stefania; Nava, Alice; Costabile, Valentino; Baiguera, Chiara; Campisi, Daniela; Fanti, Diana; Vismara, Chiara; Fumagalli, Roberto; Scaglione, Francesco; Epis, Oscar Massimiliano; Puoti, Massimo; Perno, Carlo Federico title: Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date: 2020-09-08 journal: PLoS One DOI: 10.1371/journal.pone.0236311 sha: doc_id: 294912 cord_uid: xl0wzi16 file: cache/cord-296268-kb7fgfaq.json key: cord-296268-kb7fgfaq authors: Mendonça, Luiza; Howe, Andrew; Gilchrist, James B.; Sun, Dapeng; Knight, Michael L.; Zanetti-Domingues, Laura C.; Bateman, Benji; Krebs, Anna-Sophia; Chen, Long; Radecke, Julika; Sheng, Yuewen; Li, Vivian D.; Ni, Tao; Kounatidis, Ilias; Koronfel, Mohamed A.; 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Abdullah-Al-Kamran; Islam, Abul Bashar Mir Md. Khademul title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 journal: bioRxiv DOI: 10.1101/2020.05.06.050260 sha: doc_id: 304792 cord_uid: 8sdxqmkb file: cache/cord-302707-cap2rgf7.json key: cord-302707-cap2rgf7 authors: Ng, Dianna L.; Goldgof, Gregory M.; Shy, Brian R.; Levine, Andrew G.; Balcerek, Joanna; Bapat, Sagar P.; Prostko, John; Rodgers, Mary; Coller, Kelly; Pearce, Sandra; Franz, Sergej; Du, Li; Stone, Mars; Pillai, Satish K.; Sotomayor-Gonzalez, Alicia; Servellita, Venice; Martin, Claudia Sanchez San; Granados, Andrea; Glasner, Dustin R.; Han, Lucy M.; Truong, Kent; Akagi, Naomi; Nguyen, David N.; Neumann, Neil M.; Qazi, Daniel; Hsu, Elaine; Gu, Wei; Santos, Yale A.; Custer, Brian; Green, Valerie; Williamson, Phillip; Hills, Nancy K.; Lu, Chuanyi M.; Whitman, Jeffrey D.; Stramer, Susan L.; Wang, Candace; Reyes, Kevin; Hakim, Jill M. C.; Sujishi, Kirk; Alazzeh, Fariba; Pham, Lori; Thornborrow, Edward; Oon, Ching-Ying; Miller, Steve; Kurtz, Theodore; Simmons, Graham; Hackett, John; Busch, Michael P.; Chiu, Charles Y. title: SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood date: 2020-09-17 journal: Nat Commun DOI: 10.1038/s41467-020-18468-8 sha: doc_id: 302707 cord_uid: cap2rgf7 file: cache/cord-304073-f3iwclkm.json key: cord-304073-f3iwclkm authors: Mullick, Jhinuk Basu; Simmons, Chelsey S.; Gaire, Janak title: Animal Models to Study Emerging Technologies Against SARS-CoV-2 date: 2020-07-27 journal: Cell Mol Bioeng DOI: 10.1007/s12195-020-00638-9 sha: doc_id: 304073 cord_uid: f3iwclkm file: cache/cord-303297-fiievwy7.json key: cord-303297-fiievwy7 authors: Oberemok, Volodymyr V.; Laikova, Kateryna V.; Yurchenko, Kseniya A.; Fomochkina, Irina I.; Kubyshkin, Anatolii V. title: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship date: 2020-04-30 journal: Inflamm Res DOI: 10.1007/s00011-020-01352-y sha: doc_id: 303297 cord_uid: fiievwy7 file: cache/cord-305931-0pgu2gvh.json key: cord-305931-0pgu2gvh authors: Janus, Scott E; Hajjari, Jamal; Cunningham, Michael J; Hoit, Brian D title: COVID19: a case report of thrombus in transit date: 2020-06-17 journal: Eur Heart J Case Rep DOI: 10.1093/ehjcr/ytaa189 sha: doc_id: 305931 cord_uid: 0pgu2gvh file: cache/cord-301730-flv5lnv8.json key: cord-301730-flv5lnv8 authors: Pandey, Anamika; Khan, Mohd Kamran; Hamurcu, Mehmet; Gezgin, Sait title: Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak date: 2020-10-15 journal: Front Plant Sci DOI: 10.3389/fpls.2020.568890 sha: doc_id: 301730 cord_uid: flv5lnv8 file: cache/cord-303741-1ou0cy5k.json key: cord-303741-1ou0cy5k authors: Stafstrom, Carl E.; Jantzie, Lauren L. title: COVID-19: Neurological Considerations in Neonates and Children date: 2020-09-10 journal: Children (Basel) DOI: 10.3390/children7090133 sha: doc_id: 303741 cord_uid: 1ou0cy5k file: cache/cord-304306-rxjahqwh.json key: cord-304306-rxjahqwh authors: Vlachakis, Dimitrios; Papakonstantinou, Eleni; Mitsis, Thanasis; Pierouli, Katerina; Diakou, Io; Chrousos, George; Bacopoulou, Flora title: Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date: 2020-10-08 journal: Food Chem Toxicol DOI: 10.1016/j.fct.2020.111805 sha: doc_id: 304306 cord_uid: rxjahqwh file: cache/cord-304479-uxp1kg86.json key: cord-304479-uxp1kg86 authors: Goodarzi, Pedram; Mahdavi, Farzad; Mirzaei, Rasoul; Hasanvand, Hamze; Sholeh, Mohammad; Zamani, Farhad; Sohrabi, Masodreza; Tabibzadeh, Alireza; Jeda, Ali Salimi; Niya, Mohammad Hadi Karbalaie; Keyvani, Hossein; Karampoor, Sajad title: Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments date: 2020-08-08 journal: Int Immunopharmacol DOI: 10.1016/j.intimp.2020.106885 sha: doc_id: 304479 cord_uid: uxp1kg86 file: cache/cord-304295-3mpymd8a.json key: cord-304295-3mpymd8a authors: Khan, Muhammad Muzamil; Noor, Amna; Madni*, Asadullah; Shafiq, Mudassir title: Emergence of novel coronavirus and progress toward treatment and vaccine date: 2020-06-04 journal: Rev Med Virol DOI: 10.1002/rmv.2116 sha: doc_id: 304295 cord_uid: 3mpymd8a file: cache/cord-304418-k9owyolj.json key: cord-304418-k9owyolj authors: Le Maréchal, M.; Morand, P.; Epaulard, O.; Némoz, B. title: COVID-19 in clinical practice: a narrative synthesis date: 2020-09-29 journal: Med Mal Infect DOI: 10.1016/j.medmal.2020.09.012 sha: doc_id: 304418 cord_uid: k9owyolj file: cache/cord-303517-8971aq02.json key: cord-303517-8971aq02 authors: Cajamarca-Baron, Jairo; Guavita-Navarro, Diana; Buitrago-Bohorquez, Jhon; Gallego-Cardona, Laura; Navas, Angela; Cubides, Hector; Arredondo, Ana María; Escobar, Alejandro; Rojas-Villarraga, Adriana title: SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression date: 2020-10-16 journal: nan DOI: 10.1016/j.reumae.2020.08.001 sha: doc_id: 303517 cord_uid: 8971aq02 file: cache/cord-305587-xtqvtleb.json key: cord-305587-xtqvtleb authors: Ma, Cuiqing; Su, Shan; Wang, Jiachao; Wei, Lin; Du, Lanying; Jiang, Shibo title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date: 2020-05-11 journal: Microbes Infect DOI: 10.1016/j.micinf.2020.05.004 sha: doc_id: 305587 cord_uid: xtqvtleb file: cache/cord-306581-g3d0lqxp.json key: cord-306581-g3d0lqxp authors: Khattab, Mohamed H.; Sherry, Alexander D.; Jessop, Aaron C.; Ciombor, Kristen K.; Chakravarthy, Bapsi title: Early detection of SARS-CoV-2 from staging PET-CT date: 2020-09-29 journal: J Radiat Oncol DOI: 10.1007/s13566-020-00436-w sha: doc_id: 306581 cord_uid: g3d0lqxp file: cache/cord-306373-61snvddh.json key: cord-306373-61snvddh authors: Xu, Xiao-Wei; Wu, Xiao-Xin; Jiang, Xian-Gao; Xu, Kai-Jin; Ying, Ling-Jun; Ma, Chun-Lian; Li, Shi-Bo; Wang, Hua-Ying; Zhang, Sheng; Gao, Hai-Nv; Sheng, Ji-Fang; Cai, Hong-Liu; Qiu, Yun-Qing; Li, Lan-Juan title: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series date: 2020-02-19 journal: BMJ DOI: 10.1136/bmj.m606 sha: doc_id: 306373 cord_uid: 61snvddh file: cache/cord-308110-cco3aq4n.json key: cord-308110-cco3aq4n authors: Okamoto, Mika; Toyama, Masaaki; Baba, Masanori title: The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date: 2020-07-30 journal: Antiviral Res DOI: 10.1016/j.antiviral.2020.104902 sha: doc_id: 308110 cord_uid: cco3aq4n file: cache/cord-308342-ycdok8fc.json key: cord-308342-ycdok8fc authors: Shutler, J.; Zaraska, K.; Holding, T. M.; Machnik, M.; Uppuluri, K.; Ashton, I.; Migdal, L.; Dahiya, R. title: Risk of SARS-CoV-2 infection from contaminated water systems date: 2020-06-20 journal: nan DOI: 10.1101/2020.06.17.20133504 sha: doc_id: 308342 cord_uid: ycdok8fc file: cache/cord-306177-5wefp31y.json key: cord-306177-5wefp31y authors: Iheagwam, Franklyn Nonso; Rotimi, Solomon Oladapo title: Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants date: 2020-09-12 journal: Scientifica (Cairo) DOI: 10.1155/2020/1878410 sha: doc_id: 306177 cord_uid: 5wefp31y file: cache/cord-304617-5ozf18lg.json key: cord-304617-5ozf18lg authors: Al-Khafaji, Khattab; AL-DuhaidahawiL, Dunya; Taskin Tok, Tugba title: Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2 date: 2020-05-15 journal: J Biomol Struct Dyn DOI: 10.1080/07391102.2020.1764392 sha: doc_id: 304617 cord_uid: 5ozf18lg file: cache/cord-305856-xt3zxajf.json key: cord-305856-xt3zxajf authors: Shanmugam, Chandrakumar; Mohammed, Abdul Rafi; Ravuri, Swarupa; Luthra, Vishwas; Rajagopal, Narasimhamurthy; Karre, Saritha title: COVID-2019 – A comprehensive pathology insight date: 2020-09-18 journal: Pathol Res Pract DOI: 10.1016/j.prp.2020.153222 sha: doc_id: 305856 cord_uid: xt3zxajf file: cache/cord-307701-fujejfwb.json key: cord-307701-fujejfwb authors: Gaurav, Shubham; Pandey, Shambhavi; Puvar, Apurvasinh; Shah, Tejas; Joshi, Madhvi; Joshi, Chaitanya; Kumar, Sachin title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 journal: bioRxiv DOI: 10.1101/2020.06.06.137604 sha: doc_id: 307701 cord_uid: fujejfwb file: cache/cord-308857-otsrexqu.json key: cord-308857-otsrexqu authors: Goel, Saurav; Hawi, Sara; Goel, Gaurav; Thakur, Vijay Kumar; Pearce, Oliver; Hoskins, Clare; Hussain, Tanvir; Agrawal, Anupam; Upadhyaya, Hari M.; Cross, Graham; Barber, Asa H. title: Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic date: 2020-05-28 journal: Mater Today Chem DOI: 10.1016/j.mtchem.2020.100300 sha: doc_id: 308857 cord_uid: otsrexqu file: cache/cord-308252-qwoo7b1l.json key: cord-308252-qwoo7b1l authors: Cardinale, Vincenzo; Capurso, Gabriele; Ianiro, Gianluca; Gasbarrini, Antonio; Arcidiacono, Paolo Giorgio; Alvaro, Domenico title: Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis date: 2020-09-16 journal: Dig Liver Dis DOI: 10.1016/j.dld.2020.09.009 sha: doc_id: 308252 cord_uid: qwoo7b1l file: cache/cord-308583-vtmwv8zl.json key: cord-308583-vtmwv8zl authors: Du, Qishi; Wang, Shuqing; Wei, Dongqing; Sirois, Suzanne; Chou, Kuo-Chen title: Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase date: 2005-02-15 journal: Analytical Biochemistry DOI: 10.1016/j.ab.2004.10.003 sha: doc_id: 308583 cord_uid: vtmwv8zl file: cache/cord-307860-iqk1yiw4.json key: cord-307860-iqk1yiw4 authors: Ionescu, Mihaela Ileana title: An Overview of the Crystallized Structures of the SARS-CoV-2 date: 2020-10-24 journal: Protein J DOI: 10.1007/s10930-020-09933-w sha: doc_id: 307860 cord_uid: iqk1yiw4 file: cache/cord-309289-vm0k7hfx.json key: cord-309289-vm0k7hfx authors: Rothan, Hussin A.; Stone, Shannon; Natekar, Janhavi; Kumari, Pratima; Arora, Komal; Kumar, Mukesh title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.14.041228 sha: doc_id: 309289 cord_uid: vm0k7hfx file: cache/cord-309074-pys4aa60.json key: cord-309074-pys4aa60 authors: Huang, Victoria W.; Imam, Sarah A.; Nguyen, Shaun A. title: Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist date: 2020-05-30 journal: World J Otorhinolaryngol Head Neck Surg DOI: 10.1016/j.wjorl.2020.04.008 sha: doc_id: 309074 cord_uid: pys4aa60 file: cache/cord-309418-dx6e0lri.json key: cord-309418-dx6e0lri authors: Segalés, Joaquim; Puig, Mariona; Rodon, Jordi; Avila-Nieto, Carlos; Carrillo, Jorge; Cantero, Guillermo; Terrón, Maria Teresa; Cruz, Sílvia; Parera, Mariona; Noguera-Julián, Marc; Izquierdo-Useros, Nuria; Guallar, Víctor; Vidal, Enric; Valencia, Alfonso; Blanco, Ignacio; Blanco, Julià; Clotet, Bonaventura; Vergara-Alert, Júlia title: Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain date: 2020-10-06 journal: Proc Natl Acad Sci U S A DOI: 10.1073/pnas.2010817117 sha: doc_id: 309418 cord_uid: dx6e0lri file: cache/cord-310807-p5cb6idp.json key: cord-310807-p5cb6idp authors: Kanwar, Anubhav; Selvaraju, Suresh; Esper, Frank title: Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio date: 2017-03-25 journal: Open Forum Infect Dis DOI: 10.1093/ofid/ofx052 sha: doc_id: 310807 cord_uid: p5cb6idp file: cache/cord-299093-zp07aqpm.json key: cord-299093-zp07aqpm authors: Harrison, Andrew G.; Lin, Tao; Wang, Penghua title: Mechanisms of SARS-CoV-2 transmission and pathogenesis date: 2020-10-14 journal: Trends Immunol DOI: 10.1016/j.it.2020.10.004 sha: doc_id: 299093 cord_uid: zp07aqpm file: cache/cord-309147-c3ikb81g.json key: cord-309147-c3ikb81g authors: Nadeem, Muhammad Shahid; Zamzami, Mazin A.; Choudhry, Hani; Murtaza, Bibi Nazia; Kazmi, Imran; Ahmad, Habib; Shakoori, Abdul Rauf title: Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) date: 2020-04-22 journal: Pathogens DOI: 10.3390/pathogens9040307 sha: doc_id: 309147 cord_uid: c3ikb81g file: cache/cord-307489-2liu4anc.json key: cord-307489-2liu4anc authors: Elavia, Nasha; Sharma, Nishant; Li, Si; Wang, Yichen; Milekic, Bojana title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia date: 2020-05-23 journal: Cureus DOI: 10.7759/cureus.8249 sha: doc_id: 307489 cord_uid: 2liu4anc file: cache/cord-309633-1cd74xdl.json key: cord-309633-1cd74xdl authors: Rogers, Julia H.; Link, Amy C.; McCulloch, Denise; Brandstetter, Elisabeth; Newman, Kira L.; Jackson, Michael L.; Hughes, James P.; Englund, Janet A.; Boeckh, Michael; Sugg, Nancy; Ilcisin, Misja; Sibley, Thomas R.; Fay, Kairsten; Lee, Jover; Han, Peter; Truong, Melissa; Richardson, Matthew; Nickerson, Deborah A.; Starita, Lea M.; Bedford, Trevor; Chu, Helen Y. title: Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study date: 2020-09-15 journal: Ann Intern Med DOI: 10.7326/m20-3799 sha: doc_id: 309633 cord_uid: 1cd74xdl file: cache/cord-310239-mmvuij3k.json key: cord-310239-mmvuij3k authors: Arentz, Susan; Yang, Guoyan; Goldenberg, Joshua; Beardsley, Jennifer; Myers, Stephen P.; Mertz, Dominik; Leeder, Stephen; Hunter, Jennifer title: Clinical significance summary: Preliminary results of a rapid review of zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections date: 2020-08-01 journal: Adv Integr Med DOI: 10.1016/j.aimed.2020.07.009 sha: doc_id: 310239 cord_uid: mmvuij3k file: cache/cord-311762-f6muhf3d.json key: cord-311762-f6muhf3d authors: Chen, Yu Wai; Yiu, Chin-Pang Bennu; Wong, Kwok-Yin title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates date: 2020-02-21 journal: F1000Res DOI: 10.12688/f1000research.22457.1 sha: doc_id: 311762 cord_uid: f6muhf3d file: cache/cord-309138-44qpk2vf.json key: cord-309138-44qpk2vf authors: Khanna, Kanika; Kohli, Sukhmeen Kaur; Kaur, Ravdeep; Bhardwaj, Abhay; Bhardwaj, Vinay; Ohri, Puja; Sharma, Anket; Ahmad, Ajaz; Bhardwaj, Renu; Ahmad, Parvaiz title: Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle date: 2020-10-03 journal: Phytomedicine DOI: 10.1016/j.phymed.2020.153361 sha: doc_id: 309138 cord_uid: 44qpk2vf file: cache/cord-310017-c8rd714a.json key: cord-310017-c8rd714a authors: Popa, Alexandra; Genger, Jakob-Wendelin; Nicholson, Michael; Penz, Thomas; Schmid, Daniela; Aberle, Stephan W.; Agerer, Benedikt; Lercher, Alexander; Endler, Lukas; Colaço, Henrique; Smyth, Mark; Schuster, Michael; Grau, Miguel; Martinez, Francisco; Pich, Oriol; Borena, Wegene; Pawelka, Erich; Keszei, Zsofia; Senekowitsch, Martin; Laine, Jan; Aberle, Judith H.; Redlberger-Fritz, Monika; Karolyi, Mario; Zoufaly, Alexander; Maritschnik, Sabine; Borkovec, Martin; Hufnagl, Peter; Nairz, Manfred; Weiss, Günter; Wolfinger, Michael T.; von Laer, Dorothee; Superti-Furga, Giulio; Lopez-Bigas, Nuria; Puchhammer-Stöckl, Elisabeth; Allerberger, Franz; Michor, Franziska; Bock, Christoph; Bergthaler, Andreas title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.07.15.204339 sha: doc_id: 310017 cord_uid: c8rd714a file: cache/cord-310507-5h6egve4.json key: cord-310507-5h6egve4 authors: van Doorn, Amarylle S.; Meijer, Berrie; Frampton, Chris M. A.; Barclay, Murray L.; de Boer, Nanne K. H. title: Systematic review with meta‐analysis: SARS‐CoV‐2 stool testing and the potential for faecal‐oral transmission date: 2020-08-27 journal: Aliment Pharmacol Ther DOI: 10.1111/apt.16036 sha: doc_id: 310507 cord_uid: 5h6egve4 file: cache/cord-308945-i2agpvhk.json key: cord-308945-i2agpvhk authors: Phipps, William S; SoRelle, Jeffrey A; Li, Quan-Zhen; Mahimainathan, Lenin; Araj, Ellen; Markantonis, John; Lacelle, Chantale; Balani, Jyoti; Parikh, Hiren; Solow, E Blair; Karp, David R; Sarode, Ravi; Muthukumar, Alagarraju title: SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity date: 2020-07-15 journal: Am J Clin Pathol DOI: 10.1093/ajcp/aqaa123 sha: doc_id: 308945 cord_uid: i2agpvhk file: cache/cord-309474-9h9w46eq.json key: cord-309474-9h9w46eq authors: Schiaffini, Riccardo; Barbetti, Fabrizio; Rapini, Novella; Inzaghi, Elena; Deodati, Annalisa; Patera, Ippolita P; Matteoli, Maria C; Ciampalini, Paolo; Carducci, Chiara; Lorubbio, Antonella; Schiaffini, Gabriele; Cianfarani, Stefano title: School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology date: 2020-07-03 journal: Diabetes Res Clin Pract DOI: 10.1016/j.diabres.2020.108302 sha: doc_id: 309474 cord_uid: 9h9w46eq file: cache/cord-310221-car394ou.json key: cord-310221-car394ou authors: Chandrashekar, Abishek; Liu, Jinyan; Martinot, Amanda J.; McMahan, Katherine; Mercado, Noe B.; Peter, Lauren; Tostanoski, Lisa H.; Yu, Jingyou; Maliga, Zoltan; Nekorchuk, Michael; Busman-Sahay, Kathleen; Terry, Margaret; Wrijil, Linda M.; Ducat, Sarah; Martinez, David R.; Atyeo, Caroline; Fischinger, Stephanie; Burke, John S.; Slein, Matthew D.; Pessaint, Laurent; Van Ry, Alex; Greenhouse, Jack; Taylor, Tammy; Blade, Kelvin; Cook, Anthony; Finneyfrock, Brad; Brown, Renita; Teow, Elyse; Velasco, Jason; Zahn, Roland; Wegmann, Frank; Abbink, Peter; Bondzie, Esther A.; Dagotto, Gabriel; Gebre, Makda S.; He, Xuan; Jacob-Dolan, Catherine; Kordana, Nicole; Li, Zhenfeng; Lifton, Michelle A.; Mahrokhian, Shant H.; Maxfield, Lori F.; Nityanandam, Ramya; Nkolola, Joseph P.; Schmidt, Aaron G.; Miller, Andrew D.; Baric, Ralph S.; Alter, Galit; Sorger, Peter K.; Estes, Jacob D.; Andersen, Hanne; Lewis, Mark G.; Barouch, Dan H. title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques date: 2020-05-20 journal: Science DOI: 10.1126/science.abc4776 sha: doc_id: 310221 cord_uid: car394ou file: cache/cord-311214-eqwxkwqa.json key: cord-311214-eqwxkwqa authors: Kumar, Roshan; Verma, Helianthous; Singhvi, Nirjara; Sood, Utkarsh; Gupta, Vipin; Singh, Mona; Kumari, Rashmi; Hira, Princy; Nagar, Shekhar; Talwar, Chandni; Nayyar, Namita; Anand, Shailly; Rawat, Charu Dogra; Verma, Mansi; Negi, Ram Krishan; Singh, Yogendra; Lal, Rup title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 journal: bioRxiv DOI: 10.1101/2020.03.25.006213 sha: doc_id: 311214 cord_uid: eqwxkwqa file: cache/cord-313344-rqvi2ksc.json key: cord-313344-rqvi2ksc authors: Farcas, Gabriella A.; Poutanen, Susan M.; Mazzulli, Tony; Willey, Barbara M.; Butany, Jagdish; Asa, Sylvia L.; Faure, Peter; Akhavan, Poolak; Low, Donald E.; Kain, Kevin C. title: Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus date: 2005-01-15 journal: J Infect Dis DOI: 10.1086/426870 sha: doc_id: 313344 cord_uid: rqvi2ksc file: cache/cord-311125-v9ddes3c.json key: cord-311125-v9ddes3c authors: Cooper, Keiland W.; Brann, David H.; Farruggia, Michael C.; Bhutani, Surabhi; Pellegrino, Robert; Tsukahara, Tatsuya; Weinreb, Caleb; Joseph, Paule V.; Larson, Eric D.; Parma, Valentina; Albers, Mark W.; Barlow, Linda A.; Datta, Sandeep Robert; Di Pizio, Antonella title: COVID-19 and the chemical senses: supporting players take center stage date: 2020-07-01 journal: Neuron DOI: 10.1016/j.neuron.2020.06.032 sha: doc_id: 311125 cord_uid: v9ddes3c file: cache/cord-310624-3kojrkz7.json key: cord-310624-3kojrkz7 authors: Flores-Alanis, Alejandro; Sandner-Miranda, Luisa; Delgado, Gabriela; Cravioto, Alejandro; Morales-Espinosa, Rosario title: The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789 date: 2020-08-27 journal: BMC Res Notes DOI: 10.1186/s13104-020-05242-8 sha: doc_id: 310624 cord_uid: 3kojrkz7 file: cache/cord-311114-ggcpsjk8.json key: cord-311114-ggcpsjk8 authors: Radhakrishnan, Chandni; Divakar, Mohit Kumar; Jain, Abhinav; Viswanathan, Prasanth; Bhoyar, Rahul C.; Jolly, Bani; Imran, Mohamed; Sharma, Disha; Rophina, Mercy; Ranjan, Gyan; Jose, Beena Philomina; Raman, Rajendran Vadukkoot; Kesavan, Thulaseedharan Nallaveettil; George, Kalpana; Mathew, Sheela; Poovullathil, Jayesh Kumar; Govindan, Sajeeth Kumar Keeriyatt; Nair, Priyanka Raveendranadhan; Vadekkandiyil, Shameer; Gladson, Vineeth; Mohan, Midhun; Parambath, Fairoz Cheriyalingal; Mangla, Mohit; Shamnath, Afra; Sivasubbu, Sridhar; Scaria, Vinod title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 journal: bioRxiv DOI: 10.1101/2020.09.09.289892 sha: doc_id: 311114 cord_uid: ggcpsjk8 file: cache/cord-312652-zhccmfgw.json key: cord-312652-zhccmfgw authors: Hu, Xiumei; Zhang, Ruyi; An, Taixue; Li, Qiang; Situ, Bo; Ou, Zihao; Wu, Changmeng; Yang, Biao; Tian, Peifu; Hu, Yuhai; Ping, Baohong; Wang, Qian; Zheng, Lei title: Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA date: 2020-06-20 journal: Clin Chim Acta DOI: 10.1016/j.cca.2020.06.032 sha: doc_id: 312652 cord_uid: zhccmfgw file: cache/cord-312160-2820aftb.json key: cord-312160-2820aftb authors: Ibrahim, Mahmoud A.A.; Abdelrahman, Alaa H.M.; Hussien, Taha A.; Badr, Esraa A.A.; Mohamed, Tarik A.; El−Seedi, Hesham R.; Pare, Paul W.; Efferth, Thomas; Hegazy, Mohamed Elamir F. title: In silico Drug Discovery of Major Metabolites from Spices as SARS-CoV-2 Main Protease Inhibitors date: 2020-10-08 journal: Comput Biol Med DOI: 10.1016/j.compbiomed.2020.104046 sha: doc_id: 312160 cord_uid: 2820aftb file: cache/cord-309876-l0xginsa.json key: cord-309876-l0xginsa authors: Vena, Antonio; Berruti, Marco; Adessi, Andrea; Blumetti, Pietro; Brignole, Michele; Colognato, Renato; Gaggioli, Germano; Giacobbe, Daniele Roberto; Bracci-Laudiero, Luisa; Magnasco, Laura; Signori, Alessio; Taramasso, Lucia; Varelli, Marco; Vendola, Nicoletta; Ball, Lorenzo; Robba, Chiara; Battaglini, Denise; Brunetti, Iole; Pelosi, Paolo; Bassetti, Matteo title: Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors date: 2020-08-27 journal: J Clin Med DOI: 10.3390/jcm9092780 sha: doc_id: 309876 cord_uid: l0xginsa file: cache/cord-311847-2czqs84q.json key: cord-311847-2czqs84q authors: Pennisi, Manuela; Lanza, Giuseppe; Falzone, Luca; Fisicaro, Francesco; Ferri, Raffaele; Bella, Rita title: SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date: 2020-07-31 journal: Int J Mol Sci DOI: 10.3390/ijms21155475 sha: doc_id: 311847 cord_uid: 2czqs84q file: cache/cord-313505-2lr4xara.json key: cord-313505-2lr4xara authors: Resende, Paola Cristina; Delatorre, Edson; Gräf, Tiago; Mir, Daiana; Motta, Fernando do Couto; Appolinario, Luciana Reis; da Paixão, Anna Carolina Dias; Ogrzewalska, Maria; Caetano, Braulia; dos Santos, Mirleide Cordeiro; de Almeida Ferreira, Jessylene; Santos Junior, Edivaldo Costa; da Silva, Sandro Patroca; Fernandes, Sandra Bianchini; Vianna, Lucas A; da Costa Souza, Larissa; Ferro, Jean F G; Nardy, Vanessa B; Croda, Júlio; Oliveira, Wanderson K; Abreu, André; Bello, Gonzalo; Siqueira, Marilda M title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 journal: bioRxiv DOI: 10.1101/2020.06.17.158006 sha: doc_id: 313505 cord_uid: 2lr4xara file: cache/cord-311848-8n9ee57a.json key: cord-311848-8n9ee57a authors: Giesen, Nicola; Sprute, Rosanne; Rüthrich, Maria; Khodamoradi, Yascha; Mellinghoff, Sibylle C.; Beutel, Gernot; Lueck, Catherina; Koldehoff, Michael; Hentrich, Marcus; Sandherr, Michael; Bergwelt-Baildon, Michael von; Wolf, Hans-Heinrich; Hirsch, Hans H.; Wörmann, Bernhard; Cornely, Oliver A.; Köhler, Philipp; Schalk, Enrico; Lilienfeld-Toal, Marie von title: Evidence-based Management of COVID-19 in Cancer Patients – Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) date: 2020-09-21 journal: Eur J Cancer DOI: 10.1016/j.ejca.2020.09.009 sha: doc_id: 311848 cord_uid: 8n9ee57a file: cache/cord-312305-ll29frwc.json key: cord-312305-ll29frwc authors: Sun, Shihui; Gu, Hongjing; Cao, Lei; Chen, Qi; Yang, Guan; Li, Rui-Ting; Fan, Hang; Ye, Qing; Deng, Yong-Qiang; Song, Xiaopeng; Qi, Yini; Li, Min; Lan, Jun; Feng, Rui; Guo, Yan; Qin, Si; Wang, Lei; Zhang, Yi-Fei; Zhou, Chao; Zhao, Lingna; Chen, Yuehong; Shen, Meng; Cui, Yujun; Yang, Xiao; Wang, Xinquan; Wang, Hui; Wang, Xiangxi; Qin, Cheng-Feng title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 journal: bioRxiv DOI: 10.1101/2020.11.10.377333 sha: doc_id: 312305 cord_uid: ll29frwc file: cache/cord-312670-hi3fjne4.json key: cord-312670-hi3fjne4 authors: Corman, V. 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Sophie; Duchaine, Caroline title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles date: 2020-10-28 journal: Clin Microbiol Rev DOI: 10.1128/cmr.00184-20 sha: doc_id: 316126 cord_uid: j51dik7f file: cache/cord-315288-fcx4q6mp.json key: cord-315288-fcx4q6mp authors: Hussain, Mohammed Hassan; Siddiqui, Saad; Mahmood, Sara; Valsamakis, Theodoros title: Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body date: 2020-08-27 journal: BMJ Case Rep DOI: 10.1136/bcr-2020-237787 sha: doc_id: 315288 cord_uid: fcx4q6mp file: cache/cord-315685-ute3dxwu.json key: cord-315685-ute3dxwu authors: Ehaideb, Salleh N.; Abdullah, Mashan L.; Abuyassin, Bisher; Bouchama, Abderrezak title: Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review date: 2020-10-06 journal: Crit Care DOI: 10.1186/s13054-020-03304-8 sha: doc_id: 315685 cord_uid: ute3dxwu file: cache/cord-318164-6rqi17oz.json key: cord-318164-6rqi17oz authors: Paoli, D.; Pallotti, F.; Nigro, G.; Aureli, A.; Perlorca, A.; Mazzuti, L.; Di Carlo, D.; Turriziani, O.; Lenzi, A.; Lombardo, F. title: Sperm cryopreservation during the SARS-CoV-2 pandemic date: 2020-10-10 journal: J Endocrinol Invest DOI: 10.1007/s40618-020-01438-8 sha: doc_id: 318164 cord_uid: 6rqi17oz file: cache/cord-319184-voc0eqb9.json key: cord-319184-voc0eqb9 authors: Abduljalil, Jameel M. title: Laboratory diagnosis of SARS-CoV-2: available approaches and limitations date: 2020-06-14 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2020.100713 sha: doc_id: 319184 cord_uid: voc0eqb9 file: cache/cord-315085-rucfowvv.json key: cord-315085-rucfowvv authors: Sekulic, Miroslav; Harper, Holly; Nezami, Behtash G; Shen, Daniel L; Sekulic, Simona Pichler; Koeth, Aaron T; Harding, Clifford V; Gilmore, Hannah; Sadri, Navid title: Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases date: 2020-05-26 journal: Am J Clin Pathol DOI: 10.1093/ajcp/aqaa091 sha: doc_id: 315085 cord_uid: rucfowvv file: cache/cord-319194-ukuia48s.json key: cord-319194-ukuia48s authors: Liò, Pietro; Goldman, Nick title: Phylogenomics and bioinformatics of SARS-CoV date: 2004-02-04 journal: Trends Microbiol DOI: 10.1016/j.tim.2004.01.005 sha: doc_id: 319194 cord_uid: ukuia48s file: cache/cord-317952-4oa9hfb4.json key: cord-317952-4oa9hfb4 authors: Bourgonje, Arno R.; Abdulle, Amaal Eman; Timens, Wim; Hillebrands, Jan‐Luuk; Navis, Gerjan J.; Gordijn, Sanne J.; Bolling, Marieke C.; Dijkstra, Gerard; Voors, Adriaan A.; Osterhaus, Albert D. M. E.; van der Voort, Peter H. J.; Mulder, Douwe J.; van Goor, Harry title: Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) date: 2020-05-17 journal: J Pathol DOI: 10.1002/path.5471 sha: doc_id: 317952 cord_uid: 4oa9hfb4 file: cache/cord-317355-z5tk3v3b.json key: cord-317355-z5tk3v3b authors: Dunker, Susanne; Hornick, Thomas; Szczepankiewicz, Grit; Maier, Melanie; Bastl, Maximilian; Bumberger, Jan; Treudler, Regina; Liebert, Uwe G.; Simon, Jan-Christoph title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread date: 2020-10-13 journal: Sci Total Environ DOI: 10.1016/j.scitotenv.2020.142881 sha: doc_id: 317355 cord_uid: z5tk3v3b file: cache/cord-317786-iv1br2oj.json key: cord-317786-iv1br2oj authors: Waterfield, T.; Watson, C.; Moore, R.; Ferris, K.; Tonry, C.; Watt, A. P.; McGinn, C.; Foster, S.; Evans, J.; Lyttle, M. D.; Ahmad, S.; Ladhani, S.; Corr, M.; McFetridge, L.; Mitchell, H.; Brown, K.; Amirthalingam, G.; Maney, J.-A.; Christie, S. title: Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study. date: 2020-09-02 journal: nan DOI: 10.1101/2020.08.31.20183095 sha: doc_id: 317786 cord_uid: iv1br2oj file: cache/cord-319877-izn315hb.json key: cord-319877-izn315hb authors: de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl; Munster, Vincent J. title: SARS and MERS: recent insights into emerging coronaviruses date: 2016-06-27 journal: Nat Rev Microbiol DOI: 10.1038/nrmicro.2016.81 sha: doc_id: 319877 cord_uid: izn315hb file: cache/cord-324557-4u8dja0n.json key: cord-324557-4u8dja0n authors: Leblanc, Jean‐François; Germain, Marc; Delage, Gilles; O’Brien, Sheila; Drews, Steven J.; Lewin, Antoine title: Risk of Transmission of Severe Acute Respiratory Syndrome Coronavirus‐2 by Transfusion: A Literature Review date: 2020-08-15 journal: Transfusion DOI: 10.1111/trf.16056 sha: doc_id: 324557 cord_uid: 4u8dja0n file: cache/cord-318316-9unfl966.json key: cord-318316-9unfl966 authors: Ortega, Joseph T.; Zambrano, Jose L.; Jastrzebska, Beata; Liprandi, Ferdinando; Rangel, Hector R.; Pujol, Flor H. title: Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies date: 2020-10-23 journal: Intervirology DOI: 10.1159/000512141 sha: doc_id: 318316 cord_uid: 9unfl966 file: cache/cord-321851-ku4z34lu.json key: cord-321851-ku4z34lu authors: Alosaimi, Bandar; Hamed, Maaweya E.; Naeem, Asif; Alsharef, Ali A.; AlQahtani, Saeed Y.; AlDosari, Kamel M.; Alamri, Aref A.; Al-Eisa, Kholoud; Khojah, Taghreed; Assiri, Abdullah M.; Enani, Mushira A. title: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract date: 2020-02-29 journal: Cytokine DOI: 10.1016/j.cyto.2019.154895 sha: doc_id: 321851 cord_uid: ku4z34lu file: cache/cord-321918-9jwma2y6.json key: cord-321918-9jwma2y6 authors: Xiu, Siyu; Dick, Alexej; Ju, Han; Mirzaie, Sako; Abdi, Fatemeh; Cocklin, Simon; Zhan, Peng; Liu, Xinyong title: Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities date: 2020-06-15 journal: J Med Chem DOI: 10.1021/acs.jmedchem.0c00502 sha: doc_id: 321918 cord_uid: 9jwma2y6 file: cache/cord-322811-6lebh7ca.json key: cord-322811-6lebh7ca authors: Baig, Mirza S.; Alagumuthu, Manikandan; Rajpoot, Sajjan; Saqib, Uzma title: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells date: 2020-06-26 journal: Drugs R D DOI: 10.1007/s40268-020-00312-5 sha: doc_id: 322811 cord_uid: 6lebh7ca file: cache/cord-324480-7u5lh4jx.json key: cord-324480-7u5lh4jx authors: Sharma, A.; Preece, B.; Swann, H; Fan, X.; McKenney, R.J.; Ori-McKenney, K.M.; Saffarian, S.; Vershinin, M.D. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.12.336818 sha: doc_id: 324480 cord_uid: 7u5lh4jx file: cache/cord-318934-dxipu00r.json key: cord-318934-dxipu00r authors: Matsuyama, Shutoku; Ujike, Makoto; Ishii, Koji; Fukushi, Shuetsu; Morikawa, Shigeru; Tashiro, Masato; Taguchi, Fumihiro title: Enhancement of SARS-CoV Infection by Proteases date: 2006 journal: The Nidoviruses DOI: 10.1007/978-0-387-33012-9_42 sha: doc_id: 318934 cord_uid: dxipu00r file: cache/cord-321855-7b1c2xdh.json key: cord-321855-7b1c2xdh authors: Alshami, Alanoud; Alattas, Rabab; Anan, Hadeel; Alhalimi, Abdulbary; Alfaraj, Ahmed; Al Qahtani, Hadi title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date: 2020-10-30 journal: PLoS One DOI: 10.1371/journal.pone.0241258 sha: doc_id: 321855 cord_uid: 7b1c2xdh file: cache/cord-322051-89wgv100.json key: cord-322051-89wgv100 authors: Tanasa, Ingrid Andrada; Manciuc, Carmen; Carauleanu, Alexandru; Navolan, Dan Bogdan; Bohiltea, Roxana Elena; Nemescu, Dragos title: Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known? date: 2020-05-28 journal: Exp Ther Med DOI: 10.3892/etm.2020.8808 sha: doc_id: 322051 cord_uid: 89wgv100 file: cache/cord-323061-0i5w7vm9.json key: cord-323061-0i5w7vm9 authors: Kharel Sitaula, Ranju; Khatri, Anadi; Janani, M K; Mandage, Rajendra; Sadhu, Soumen; Madhavan, H N; Upadhyay, Madan Prasad; Biswas, Jyotirmay title: Unfolding COVID-19: Lessons-in-Learning in Ophthalmology date: 2020-09-28 journal: Clin Ophthalmol DOI: 10.2147/opth.s259857 sha: doc_id: 323061 cord_uid: 0i5w7vm9 file: cache/cord-319241-div9rzax.json key: cord-319241-div9rzax authors: Singh, Bhuchitra; Gornet, Megan; Sims, Holly; Kisanga, Edwina; Knight, Zachary; Segars, James title: Severe Acute Respiratory Syndrome‐Corona Virus‐2 (SARS‐CoV‐2) and its Effect on Gametogenesis and Early Pregnancy date: 2020-09-23 journal: Am J Reprod Immunol DOI: 10.1111/aji.13351 sha: doc_id: 319241 cord_uid: div9rzax file: cache/cord-320619-r466dc5t.json key: cord-320619-r466dc5t authors: Chand Dakal, Tikam title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 date: 2020-11-05 journal: Immunobiology DOI: 10.1016/j.imbio.2020.152021 sha: doc_id: 320619 cord_uid: r466dc5t file: cache/cord-322908-e3gok0ot.json key: cord-322908-e3gok0ot authors: Huang, Fangfang; Li, Ying; Leung, Elaine Lai-Han; Liu, Xiaohua; Liu, Kaifeng; Wang, Qu; Lan, Yongqi; Li, Xiaoling; Yu, Haibing; Cu, Liao; Luo, Hui; Luo, Lianxiang title: A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) date: 2020-05-20 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.104929 sha: doc_id: 322908 cord_uid: e3gok0ot file: cache/cord-321166-nvphu1fm.json key: cord-321166-nvphu1fm authors: Thomson, Emma C.; Rosen, Laura E.; Shepherd, James G.; Spreafico, Roberto; da Silva Filipe, Ana; Wojcechowskyj, Jason A.; Davis, Chris; Piccoli, Luca; Pascall, David J.; Dillen, Josh; Lytras, Spyros; Czudnochowski, Nadine; Shah, Rajiv; Meury, Marcel; Jesudason, Natasha; De Marco, Anna; Li, Kathy; Bassi, Jessica; O’Toole, Aine; Pinto, Dora; Colquhoun, Rachel M.; Culap, Katja; Jackson, Ben; Zatta, Fabrizia; Rambaut, Andrew; Jaconi, Stefano; Sreenu, Vattipally B.; Nix, Jay; Jarrett, Ruth F.; Beltramello, Martina; Nomikou, Kyriaki; Pizzuto, Matteo; Tong, Lily; Cameroni, Elisabetta; Johnson, Natasha; Wickenhagen, Arthur; Ceschi, Alessandro; Mair, Daniel; Ferrari, Paolo; Smollett, Katherine; Sallusto, Federica; Carmichael, Stephen; Garzoni, Christian; Nichols, Jenna; Galli, Massimo; Hughes, Joseph; Riva, Agostino; Ho, Antonia; Semple, Malcolm G.; Openshaw, Peter J.M.; Baillie, J. 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Yukthamarani; Agho, Kingsley E. title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys date: 2020-07-21 journal: Int J Environ Res Public Health DOI: 10.3390/ijerph17145252 sha: doc_id: 324856 cord_uid: hf969tav file: cache/cord-328000-i9tzr13z.json key: cord-328000-i9tzr13z authors: Cockrell, Adam S.; Leist, Sarah R.; Douglas, Madeline G.; Baric, Ralph S. title: Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice date: 2018-07-24 journal: Mamm Genome DOI: 10.1007/s00335-018-9760-9 sha: doc_id: 328000 cord_uid: i9tzr13z file: cache/cord-326013-5i35zdmv.json key: cord-326013-5i35zdmv authors: Carpinteiro, Alexander; Edwards, Michael J.; Hoffmann, Markus; Kochs, Georg; Gripp, Barbara; Weigang, Sebastian; Adams, Constantin; Carpinteiro, Elisa; Gulbins, Anne; Keitsch, Simone; Sehl, Carolin; Soddemann, Matthias; Wilker, Barbara; Kamler, Markus; Bertsch, Thomas; Lang, Karl S.; Patel, Sameer; Wilson, Gregory C.; Walter, Silke; Hengel, Hartmut; Pöhlmann, Stefan; Lang, Philipp; Kornhuber, Johannes; Becker, Katrin Anne; Ahmad, Syed A.; Fassbender, Klaus; Gulbins, Erich title: Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells date: 2020-10-29 journal: Cell Rep Med DOI: 10.1016/j.xcrm.2020.100142 sha: doc_id: 326013 cord_uid: 5i35zdmv file: cache/cord-326017-qw4qynqv.json key: cord-326017-qw4qynqv authors: Laskar, Partha; Yallapu, Murali M.; Chauhan, Subhash C. title: “Tomorrow Never Dies”: Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies date: 2020-08-06 journal: Diseases DOI: 10.3390/diseases8030030 sha: doc_id: 326017 cord_uid: qw4qynqv file: cache/cord-329011-spiuqngp.json key: cord-329011-spiuqngp authors: Huang, Yuan; Yang, Chan; Xu, Xin-feng; Xu, Wei; Liu, Shu-wen title: Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 date: 2020-08-03 journal: Acta Pharmacol Sin DOI: 10.1038/s41401-020-0485-4 sha: doc_id: 329011 cord_uid: spiuqngp file: cache/cord-331039-qgom2e3n.json key: cord-331039-qgom2e3n authors: Kavitha, Kuppuswamy; Sivakumar, Subramaniam; Ramesh, Balasubramanian title: 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates date: 2020-09-22 journal: Biophys Chem DOI: 10.1016/j.bpc.2020.106478 sha: doc_id: 331039 cord_uid: qgom2e3n file: cache/cord-328361-hyrke6j2.json key: cord-328361-hyrke6j2 authors: Ithete, Ndapewa Laudika; Stoffberg, Samantha; Corman, Victor Max; Cottontail, Veronika M.; Richards, Leigh Rosanne; Schoeman, M. 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Katterine; Rodriguez-Morales, Alfonso J. title: SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus date: 2020-08-02 journal: Travel Med Infect Dis DOI: 10.1016/j.tmaid.2020.101830 sha: doc_id: 327063 cord_uid: ea7a1xfl file: cache/cord-329010-n0mz098o.json key: cord-329010-n0mz098o authors: McKee, Dwight L.; Sternberg, Ariane; Stange, Ulrike; Laufer, Stefan; Naujokat, Cord title: Candidate drugs against SARS-CoV-2 and COVID-19 date: 2020-04-29 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.104859 sha: doc_id: 329010 cord_uid: n0mz098o file: cache/cord-329493-ueqlhgn0.json key: cord-329493-ueqlhgn0 authors: Stadler, Konrad; Masignani, Vega; Eickmann, Markus; Becker, Stephan; Abrignani, Sergio; Klenk, Hans-Dieter; Rappuoli, Rino title: SARS — beginning to understand a new virus date: 2003 journal: Nat Rev Microbiol DOI: 10.1038/nrmicro775 sha: doc_id: 329493 cord_uid: ueqlhgn0 file: cache/cord-332948-h297ukuu.json key: cord-332948-h297ukuu authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date: 2020-10-16 journal: Inform Med Unlocked DOI: 10.1016/j.imu.2020.100451 sha: doc_id: 332948 cord_uid: h297ukuu file: cache/cord-328003-yovp8squ.json key: cord-328003-yovp8squ authors: Duan, Liangwei; Zheng, Qianqian; Zhang, Hongxia; Niu, Yuna; Lou, Yunwei; Wang, Hui title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.576622 sha: doc_id: 328003 cord_uid: yovp8squ file: cache/cord-328289-3h3kmjlz.json key: cord-328289-3h3kmjlz authors: Iadecola, Costantino; Anrather, Josef; Kamel, Hooman title: Effects of COVID-19 on the nervous system date: 2020-08-19 journal: Cell DOI: 10.1016/j.cell.2020.08.028 sha: doc_id: 328289 cord_uid: 3h3kmjlz file: cache/cord-330343-p7a8chn4.json key: cord-330343-p7a8chn4 authors: Kelly-Cirino, Cassandra; Mazzola, Laura T; Chua, Arlene; Oxenford, Christopher J; Van Kerkhove, Maria D title: An updated roadmap for MERS-CoV research and product development: focus on diagnostics date: 2019-02-01 journal: BMJ Glob Health DOI: 10.1136/bmjgh-2018-001105 sha: doc_id: 330343 cord_uid: p7a8chn4 file: cache/cord-332595-874tpi09.json key: cord-332595-874tpi09 authors: Salehi, Najmeh; Amiri-Yekta, Amir; Totonchi, Mehdi title: Profiling of Initial Available SARS-CoV-2 Sequences from Iranian Related COVID-19 Patients date: 2020-09-08 journal: Cell J DOI: 10.22074/cellj.2020.7524 sha: doc_id: 332595 cord_uid: 874tpi09 file: cache/cord-330597-nftwj0d5.json key: cord-330597-nftwj0d5 authors: Hopfer, Helmut; Herzig, Martin C.; Gosert, Rainer; Menter, Thomas; Hench, Jürgen; Tzankov, Alexandar; Hirsch, Hans H.; Miller, Sara E. title: Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues date: 2020-09-27 journal: Histopathology DOI: 10.1111/his.14264 sha: doc_id: 330597 cord_uid: nftwj0d5 file: cache/cord-331472-kd4uxcve.json key: cord-331472-kd4uxcve authors: Shahid, Zainab; Kalayanamitra, Ricci; McClafferty, Brendan; Kepko, Douglas; Ramgobin, Devyani; Patel, Ravi; Aggarwal, Chander Shekher; Vunnam, Ramarao; Sahu, Nitasa; Bhatt, Dhirisha; Jones, Kirk; Golamari, Reshma; Jain, Rohit title: COVID‐19 and Older Adults: What We Know date: 2020-04-20 journal: J Am Geriatr Soc DOI: 10.1111/jgs.16472 sha: doc_id: 331472 cord_uid: kd4uxcve file: cache/cord-332080-923jpec0.json key: cord-332080-923jpec0 authors: Lai, Chih-Cheng; Wang, Cheng-Yi; Ko, Wen-Chien; Hsueh, Po-Ren title: In vitro diagnostics of coronavirus disease 2019: technologies and application date: 2020-06-05 journal: J Microbiol Immunol Infect DOI: 10.1016/j.jmii.2020.05.016 sha: doc_id: 332080 cord_uid: 923jpec0 file: cache/cord-332448-5fz8ef4f.json key: cord-332448-5fz8ef4f authors: Mutnal, M. B.; Arroliga, A. C.; Walker, K.; Mohammad, A. A.; Brigmon, M. M.; Beaver, R. M.; Midturi, J. K.; Rao, A. title: Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses date: 2020-05-02 journal: nan DOI: 10.1101/2020.04.30.20086116 sha: doc_id: 332448 cord_uid: 5fz8ef4f file: cache/cord-331193-33cyvidx.json key: cord-331193-33cyvidx authors: Mawhinney, Jamie A; Wilcock, Catherine; Haboubi, Hasan; Roshanzamir, Shahbaz title: Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode date: 2020-06-14 journal: BMJ Case Rep DOI: 10.1136/bcr-2020-236123 sha: doc_id: 331193 cord_uid: 33cyvidx file: cache/cord-332778-rf47ptj6.json key: cord-332778-rf47ptj6 authors: Vivarelli, Silvia; Falzone, Luca; Grillo, Caterina Maria; Scandurra, Giuseppa; Torino, Francesco; Libra, Massimo title: Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial? date: 2020-08-10 journal: Cancers (Basel) DOI: 10.3390/cancers12082237 sha: doc_id: 332778 cord_uid: rf47ptj6 file: cache/cord-331856-j0gedx43.json key: cord-331856-j0gedx43 authors: Basile, K.; Maddocks, S.; Kok, J.; Dwyer, D.E. title: Accuracy amidst ambiguity: false positive SARS-CoV-2 nucleic acid tests when COVID-19 prevalence is low date: 2020-09-30 journal: Pathology DOI: 10.1016/j.pathol.2020.09.009 sha: doc_id: 331856 cord_uid: j0gedx43 file: cache/cord-333326-n9ifhw5s.json key: cord-333326-n9ifhw5s authors: Wardell, Hanna; Campbell, Jeffrey I; VanderPluym, Christina; Dixit, Avika title: Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates date: 2020-07-09 journal: J Pediatric Infect Dis Soc DOI: 10.1093/jpids/piaa084 sha: doc_id: 333326 cord_uid: n9ifhw5s file: cache/cord-332723-rz1iilsv.json key: cord-332723-rz1iilsv authors: Creager, Hannah M.; Cabrera, Barbara; Schnaubelt, Andy; Cox, Jesse L.; Cushman-Vokoun, Allison M.; Shakir, Salika M.; Tardif, Keith D.; Huang, Meei-Li; Jerome, Keith R.; Greninger, Alexander L.; Drobysheva, Daria; Spaulding, Usha; Rogatcheva, Margarita; Bourzac, Kevin M.; Hinrichs, S.H.; Broadhurst, M.J.; Fey, P.D. title: Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2 date: 2020-07-06 journal: J Clin Virol DOI: 10.1016/j.jcv.2020.104538 sha: doc_id: 332723 cord_uid: rz1iilsv file: cache/cord-333547-88dkh6xd.json key: cord-333547-88dkh6xd authors: Hasan, Shadi W.; Ibrahim, Yazan; Daou, Marianne; Kannout, Hussein; Jan, Nila; Lopes, Alvaro; Alsafar, Habiba; Yousef, Ahmed F. title: Detection and Quantification of SARS-CoV-2 RNA in Wastewater and Treated Effluents: Surveillance of COVID-19 Epidemic in the United Arab Emirates date: 2020-10-19 journal: Sci Total Environ DOI: 10.1016/j.scitotenv.2020.142929 sha: doc_id: 333547 cord_uid: 88dkh6xd file: cache/cord-333682-ktbnrkwh.json key: cord-333682-ktbnrkwh authors: Dong, Yunzhu; Chi, Xiangyang; Hai, Huang; Sun, Liangliang; Zhang, Mengyao; Xie, Wei-Fen; Chen, Wei title: Antibodies in the breast milk of a maternal woman with COVID-19 date: 2020-07-03 journal: Emerging microbes & infections DOI: 10.1080/22221751.2020.1780952 sha: doc_id: 333682 cord_uid: ktbnrkwh file: cache/cord-332992-8rmqg4rf.json key: cord-332992-8rmqg4rf authors: de Vries, A. A. 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Kelly; Gerber, Susan I.; Jones, Tara L.; Metcalfe, Maureen G.; Tong, Suxiang; Tao, Ying; Alami, Negar N.; Haynes, Lia M.; Mutei, Mowafaq Ali; Abdel-Wareth, Laila; Uyeki, Timothy M.; Swerdlow, David L.; Barakat, Maha; Zaki, Sherif R. title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 date: 2016-03-31 journal: The American Journal of Pathology DOI: 10.1016/j.ajpath.2015.10.024 sha: doc_id: 339762 cord_uid: lh8czr0a file: cache/cord-339859-anatn295.json key: cord-339859-anatn295 authors: Paret, Michal; Lighter, Jennifer; Pellett Madan, Rebecca; Raabe, Vanessa N; Shust, Gail F; Ratner, Adam J title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress date: 2020-04-17 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa452 sha: doc_id: 339859 cord_uid: anatn295 file: cache/cord-340305-jtvn9tlm.json key: cord-340305-jtvn9tlm authors: Cimolai, Nevio title: A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19 date: 2020-09-19 journal: SN Compr Clin Med DOI: 10.1007/s42399-020-00533-4 sha: doc_id: 340305 cord_uid: jtvn9tlm file: cache/cord-338436-0z828org.json key: cord-338436-0z828org authors: Tzou, Philip L.; Tao, Kaiming; Nouhin, Janin; Rhee, Soo-Yon; Hu, Benjamin D.; Pai, Shruti; Parkin, Neil; Shafer, Robert W. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 journal: Viruses DOI: 10.3390/v12091006 sha: doc_id: 338436 cord_uid: 0z828org file: cache/cord-339665-nwwutduy.json key: cord-339665-nwwutduy authors: Patel, Ami; Walters, Jewell; Reuschel, Emma L.; Schultheis, Katherine; Parzych, Elizabeth; Gary, Ebony N.; Maricic, Igor; Purwar, Mansi; Eblimit, Zeena; Walker, Susanne N.; Guimet, Diana; Bhojnagarwala, Pratik; Doan, Arthur; Xu, Ziyang; Elwood, Dustin; Reeder, Sophia M.; Pessaint, Laurent; Kim, Kevin Y.; Cook, Anthony; Chokkalingam, Neethu; Finneyfrock, Brad; Tello-Ruiz, Edgar; Dodson, Alan; Choi, Jihae; Generotti, Alison; Harrison, John; Tursi, Nicholas J.; Andrade, Viviane M.; Dia, Yaya; Zaidi, Faraz I.; Andersen, Hanne; Lewis, Mark G.; Muthumani, Kar; Kim, J Joseph; Kulp, Daniel W.; Humeau, Laurent M.; Ramos, Stephanie; Smith, Trevor R.F.; Weiner, David B.; Broderick, Kate E. title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 journal: bioRxiv DOI: 10.1101/2020.07.28.225649 sha: doc_id: 339665 cord_uid: nwwutduy file: cache/cord-342220-lrqt2gcw.json key: cord-342220-lrqt2gcw authors: Dearlove, Bethany; Lewitus, Eric; Bai, Hongjun; Li, Yifan; Reeves, Daniel B.; Joyce, M. Gordon; Scott, Paul T.; Amare, Mihret F.; Vasan, Sandhya; Michael, Nelson L.; Modjarrad, Kayvon; Rolland, Morgane title: A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants date: 2020-09-22 journal: Proc Natl Acad Sci U S A DOI: 10.1073/pnas.2008281117 sha: doc_id: 342220 cord_uid: lrqt2gcw file: cache/cord-342383-ckswlo9o.json key: cord-342383-ckswlo9o authors: Pawlowski, C.; Puranik, A.; Bandi, H.; Venkatakrishnan, A.; Agarwal, V.; Kennedy, R.; O'Horo, J. C.; Gores, G. J.; Williams, A. W.; Halamka, J.; Badley, A. 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G.; de Graaf, M. title: Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing date: 2020-09-22 journal: nan DOI: 10.1101/2020.09.21.20198838 sha: doc_id: 342538 cord_uid: 5bwsm290 file: cache/cord-343196-vlwzzrgc.json key: cord-343196-vlwzzrgc authors: Kiambi, Stella; Corman, Victor M.; Sitawa, Rina; Githinji, Jane; Ngoci, James; Ozomata, Abdullahi S.; Gardner, Emma; von Dobschuetz, Sophie; Morzaria, Subhash; Kimutai, Joshua; Schroeder, Simon; Njagi, Obadiah; Simpkin, Piers; Rugalema, Gabriel; Tadesse, Zelalem; Lubroth, Juan; Makonnen, Yilma; Drosten, Christian; Müller, Marcel A.; Fasina, Folorunso O. title: Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017 date: 2018-11-28 journal: Emerg Microbes Infect DOI: 10.1038/s41426-018-0193-z sha: doc_id: 343196 cord_uid: vlwzzrgc file: cache/cord-343528-5283jsnu.json key: cord-343528-5283jsnu authors: Zhang, Zhao; Shen, Libing; Gu, Xun title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date: 2016-05-04 journal: Sci Rep DOI: 10.1038/srep25049 sha: doc_id: 343528 cord_uid: 5283jsnu file: cache/cord-346819-11fkgzaa.json key: cord-346819-11fkgzaa authors: Khan, Mohd Imran; Khan, Zainul A.; Baig, Mohammad Hassan; Ahmad, Irfan; Farouk, Abd-ElAziem; Song, Young Goo; Dong, Jae-Jun title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 journal: PLoS One DOI: 10.1371/journal.pone.0238344 sha: doc_id: 346819 cord_uid: 11fkgzaa file: cache/cord-343302-g9vcchrh.json key: cord-343302-g9vcchrh authors: Agrawal, Anurodh Shankar; Ying, Tianlei; Tao, Xinrong; Garron, Tania; Algaissi, Abdullah; Wang, Yanping; Wang, Lili; Peng, Bi-Hung; Jiang, Shibo; Dimitrov, Dimiter S.; Tseng, Chien-Te K. title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date: 2016-08-19 journal: Sci Rep DOI: 10.1038/srep31629 sha: doc_id: 343302 cord_uid: g9vcchrh file: cache/cord-342756-rgm9ffpk.json key: cord-342756-rgm9ffpk authors: Senger, Mario Roberto; Evangelista, Tereza Cristina Santos; Dantas, Rafael Ferreira; Santana, Marcos Vinicius da Silva; Gonçalves, Luiz Carlos Saramago; de Souza Neto, Lauro Ribeiro; Ferreira, Sabrina Baptista; Silva-Junior, Floriano Paes title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 journal: Mem Inst Oswaldo Cruz DOI: 10.1590/0074-02760200254 sha: doc_id: 342756 cord_uid: rgm9ffpk file: cache/cord-348192-ibohbjfb.json key: cord-348192-ibohbjfb authors: Odih, Erkison E.; Afolayan, Ayorinde O.; Akintayo, IfeOluwa; Okeke, Iruka N. title: Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? date: 2020-06-09 journal: Am J Trop Med Hyg DOI: 10.4269/ajtmh.20-0462 sha: doc_id: 348192 cord_uid: ibohbjfb file: cache/cord-343517-vf32wxkx.json key: cord-343517-vf32wxkx authors: Lokman, Syed Mohammad; Rasheduzzaman, Md.; Salauddin, Asma; Barua, Rocktim; Tanzina, Afsana Yeasmin; Rumi, Meheadi Hasan; Hossain, Md. Imran; Siddiki, Amam Zonaed; Mannan, Adnan; Hasan, Md. Mahbub title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.07.030924 sha: doc_id: 343517 cord_uid: vf32wxkx file: cache/cord-346960-3empldlo.json key: cord-346960-3empldlo authors: Plebani, M.; Padoan, A.; Sciacovelli, L.; Bonfante, F.; Pagliari, M.; Bozzato, D.; Cosma, C.; Bortolami, A.; Negrini, D.; Zuin, S. title: Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity date: 2020-08-04 journal: nan DOI: 10.1101/2020.08.01.20166546 sha: doc_id: 346960 cord_uid: 3empldlo file: cache/cord-345371-pjbviagq.json key: cord-345371-pjbviagq authors: Lisi, Lucia; Lacal, Pedro Miguel; Barbaccia, Maria Luisa; Graziani, Grazia title: Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2 date: 2020-07-23 journal: Biochem Pharmacol DOI: 10.1016/j.bcp.2020.114169 sha: doc_id: 345371 cord_uid: pjbviagq file: cache/cord-341453-9yrvjlpx.json key: cord-341453-9yrvjlpx authors: Clay, Candice C; Donart, Nathan; Fomukong, Ndingsa; Knight, Jennifer B; Overheim, Katie; Tipper, Jennifer; Van Westrienen, Jesse; Hahn, Fletcher; Harrod, Kevin S title: Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses date: 2014-03-19 journal: Immun Ageing DOI: 10.1186/1742-4933-11-4 sha: doc_id: 341453 cord_uid: 9yrvjlpx file: cache/cord-346987-fbqqf00i.json key: cord-346987-fbqqf00i authors: Guo, Yongwen; Jing, Yan; Wang, Yunshi; To, Aileen; Du, Shufang; Wang, Liuzheng; Bai, Ding title: Controls of SARS-CoV-2 transmission in orthodontic practice date: 2020-06-05 journal: Am J Orthod Dentofacial Orthop DOI: 10.1016/j.ajodo.2020.05.006 sha: doc_id: 346987 cord_uid: fbqqf00i file: cache/cord-348696-86nbwon2.json key: cord-348696-86nbwon2 authors: Güemes-Villahoz, Noemi; Burgos-Blasco, Barbara; Vidal-Villegas, Beatriz; Garcia-Feijoo, Julián; Arriola-Villalobos, Pedro; Martínez-de-la-Casa, Jose María; Diaz-Valle, David; Konstas, Anastasios G. title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review date: 2020-08-18 journal: Adv Ther DOI: 10.1007/s12325-020-01442-7 sha: doc_id: 348696 cord_uid: 86nbwon2 file: cache/cord-347706-r0rs3ls1.json key: cord-347706-r0rs3ls1 authors: Roberts, Anjeanette; Subbarao, Kanta title: Animal Models for Sars date: 2006 journal: The Nidoviruses DOI: 10.1007/978-0-387-33012-9_83 sha: doc_id: 347706 cord_uid: r0rs3ls1 file: cache/cord-345381-9cckppk2.json key: cord-345381-9cckppk2 authors: Klimek, Ludger; Pfaar, Oliver; Worm, Margitta; Eiwegger, Thomas; Hagemann, Jan; Ollert, Markus; Untersmayr, Eva; Hoffmann-Sommergruber, Karin; Vultaggio, Alessandra; Agache, Ioana; Bavbek, Sevim; Bossios, Apostolos; Casper, Ingrid; Chan, Susan; Chatzipetrou, Alexia; Vogelberg, Christian; Firinu, Davide; Kauppi, Paula; Kolios, Antonios; Kothari, Akash; Matucci, Andrea; Palomares, Oscar; Szépfalusi, Zsolt; Pohl, Wolfgang; Hötzenecker, Wolfram; Rosenkranz, Alexander R.; Bergmann, Karl-Christian; Bieber, Thomas; Buhl, Roland; Buters, Jeroen; Darsow, Ulf; Keil, Thomas; Kleine-Tebbe, Jörg; Lau, Susanne; Maurer, Marcus; Merk, Hans; Mösges, Ralph; Saloga, Joachim; Staubach, Petra; Jappe, Uta; Rabe, Klaus F.; Rabe, Uta; Vogelmeier, Claus; Biedermann, Tilo; Jung, Kirsten; Schlenter, Wolfgang; Ring, Johannes; Chaker, Adam; Wehrmann, Wolfgang; Becker, Sven; Freudelsperger, Laura; Mülleneisen, Norbert; Nemat, Katja; Czech, Wolfgang; Wrede, Holger; Brehler, Randolf; Fuchs, Thomas; Tomazic, Peter-Valentin; Aberer, Werner; Fink-Wagner, Antje-Henriette; Horak, Fritz; Wöhrl, Stefan; Niederberger-Leppin, Verena; Pali-Schöll, Isabella; Pohl, Wolfgang; Roller-Wirnsberger, Regina; Spranger, Otto; Valenta, Rudolf; Akdis, Mübecell; Matricardi, Paolo M.; Spertini, François; Khaltaev, Nicolai; Michel, Jean-Pierre; Nicod, Larent; Schmid-Grendelmeier, Peter; Idzko, Marco; Hamelmann, Eckard; Jakob, Thilo; Werfel, Thomas; Wagenmann, Martin; Taube, Christian; Jensen-Jarolim, Erika; Korn, Stephanie; Hentges, Francois; Schwarze, Jürgen; O´Mahony, Liam; Knol, Edward F.; del Giacco, Stefano; Chivato Pérez, Tomás; Bousquet, Jean; Bedbrook, Anna; Zuberbier, Torsten; Akdis, Cezmi; Jutel, Marek title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) date: 2020-09-07 journal: Allergol Select DOI: 10.5414/alx02166e sha: doc_id: 345381 cord_uid: 9cckppk2 file: cache/cord-344714-0cam9ipf.json key: cord-344714-0cam9ipf authors: Russo, Maria; Moccia, Stefania; Spagnuolo, Carmela; Tedesco, Idolo; Russo, Gian Luigi title: Roles of flavonoids against coronavirus infection date: 2020-07-28 journal: Chem Biol Interact DOI: 10.1016/j.cbi.2020.109211 sha: doc_id: 344714 cord_uid: 0cam9ipf file: cache/cord-348384-8cvt1fo6.json key: cord-348384-8cvt1fo6 authors: Butsashvili, M.; Gulbiani, L.; Kanchelashvili, G.; Kochlamazashvili, M.; Nioradze, G.; Kamkamidze, G. title: Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population date: 2020-05-19 journal: nan DOI: 10.1101/2020.05.14.20101642 sha: doc_id: 348384 cord_uid: 8cvt1fo6 file: cache/cord-348821-2u6ki9dv.json key: cord-348821-2u6ki9dv authors: Xu, Ping; Sun, Guo-Dong; Li, Zhi-Zhong title: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. date: 2020-03-10 journal: nan DOI: 10.1101/2020.03.08.20032821 sha: doc_id: 348821 cord_uid: 2u6ki9dv file: cache/cord-349117-xfir3m5p.json key: cord-349117-xfir3m5p authors: Hyseni, Inesa; Molesti, Eleonora; Benincasa, Linda; Piu, Pietro; Casa, Elisa; Temperton, Nigel J; Manenti, Alessandro; Montomoli, Emanuele title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 journal: Viruses DOI: 10.3390/v12091011 sha: doc_id: 349117 cord_uid: xfir3m5p file: cache/cord-345929-z7yfegr5.json key: cord-345929-z7yfegr5 authors: Thakur, Suman S. title: Proteomics and Its Application in Pandemic Diseases date: 2020-11-06 journal: J Proteome Res DOI: 10.1021/acs.jproteome.0c00824 sha: doc_id: 345929 cord_uid: z7yfegr5 file: cache/cord-348301-bk80pps9.json key: cord-348301-bk80pps9 authors: Wahl, Angela; Gralinski, Lisa; Johnson, Claire; Yao, Wenbo; Kovarova, Martina; Dinnon, Kenneth; Liu, Hongwei; Madden, Victoria; Krzystek, Halina; De, Chandrav; White, Kristen; Schäfer, Alexandra; Zaman, Tanzila; Leist, Sarah; Grant, Paul; Gully, Kendra; Askin, Frederic; Browne, Edward; Jones, Corbin; Pickles, Raymond; Baric, Ralph; Garcia, J Victor title: Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 date: 2020-09-24 journal: Res Sq DOI: 10.21203/rs.3.rs-80404/v1 sha: doc_id: 348301 cord_uid: bk80pps9 file: cache/cord-347460-9vechh4x.json key: cord-347460-9vechh4x authors: Chang, Feng-Yee; Chen, Hsiang-Cheng; Chen, Pei-Jer; Ho, Mei-Shang; Hsieh, Shie-Liang; Lin, Jung-Chung; Liu, Fu-Tong; Sytwu, Huey-Kang title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 journal: J Biomed Sci DOI: 10.1186/s12929-020-00663-w sha: doc_id: 347460 cord_uid: 9vechh4x file: cache/cord-348899-vynk8q8c.json key: cord-348899-vynk8q8c authors: Jo, Seri; Kim, Suwon; Shin, Dong Hae; Kim, Mi-Sun title: Inhibition of SARS-CoV 3CL protease by flavonoids date: 2019-11-14 journal: J Enzyme Inhib Med Chem DOI: 10.1080/14756366.2019.1690480 sha: doc_id: 348899 cord_uid: vynk8q8c file: cache/cord-349643-jtx7ni9b.json key: cord-349643-jtx7ni9b authors: Uyeki, Timothy M.; Erlandson, Karl J.; Korch, George; O’Hara, Michael; Wathen, Michael; Hu-Primmer, Jean; Hojvat, Sally; Stemmy, Erik J.; Donabedian, Armen title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus date: 2016-07-17 journal: Emerg Infect Dis DOI: 10.3201/eid2207.160022 sha: doc_id: 349643 cord_uid: jtx7ni9b file: cache/cord-346777-zmmnn9b2.json key: cord-346777-zmmnn9b2 authors: Lester, Sandra; Harcourt, Jennifer; Whitt, Michael; Al-Abdely, Hail M.; Midgley, Claire M.; Alkhamis, Abdulrahim M.; Aziz Jokhdar, Hani A.; Assiri, Abdullah M.; Tamin, Azaibi; Thornburg, Natalie title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies date: 2019-09-11 journal: Access Microbiol DOI: 10.1099/acmi.0.000057 sha: doc_id: 346777 cord_uid: zmmnn9b2 file: cache/cord-345356-gn1iwis0.json key: cord-345356-gn1iwis0 authors: Glebov, Oleg O. title: Understanding SARS‐CoV‐2 endocytosis for COVID‐19 drug repurposing date: 2020-06-02 journal: FEBS J DOI: 10.1111/febs.15369 sha: doc_id: 345356 cord_uid: gn1iwis0 file: cache/cord-350505-uh8r2vyz.json key: cord-350505-uh8r2vyz authors: Kalantar-Zadeh, Kourosh; Ward, Stephanie A.; Kalantar-Zadeh, Kamyar; El-Omar, Emad M. title: Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles date: 2020-05-01 journal: ACS Nano DOI: 10.1021/acsnano.0c03402 sha: doc_id: 350505 cord_uid: uh8r2vyz file: cache/cord-350015-mg5wiihj.json key: cord-350015-mg5wiihj authors: Chen, Yiyin; Klein, Sabra L.; Garibaldi, Brian T.; Li, Huifen; Wu, Cunjin; Osevala, Nicole M.; Li, Taisheng; Margolick, Joseph B.; Pawelec, Graham; Leng, Sean X. title: Aging in COVID-19: Vulnerability, immunity and intervention date: 2020-10-31 journal: Ageing Res Rev DOI: 10.1016/j.arr.2020.101205 sha: doc_id: 350015 cord_uid: mg5wiihj file: cache/cord-347767-aq9niccc.json key: cord-347767-aq9niccc authors: Zhao, Jie; Yang, Xiaodong; Wang, Chenghua; Song, Shuai; Cao, Kun; Wei, Taohua; Ji, Qiaoxue; Zheng, Wanqun; Li, Jiali; Zhou, Xue; Liu, Jie title: Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a date: 2020-06-19 journal: Biomed Pharmacother DOI: 10.1016/j.biopha.2020.110436 sha: doc_id: 347767 cord_uid: aq9niccc file: cache/cord-349682-kpg0vley.json key: cord-349682-kpg0vley authors: Ojha, Probir Kumar; Kar, Supratik; Krishna, Jillella Gopala; Roy, Kunal; Leszczynski, Jerzy title: Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to date: 2020-09-02 journal: Mol Divers DOI: 10.1007/s11030-020-10134-x sha: doc_id: 349682 cord_uid: kpg0vley file: cache/cord-350557-7i7122zi.json key: cord-350557-7i7122zi authors: Rawlings, Stephen A; Ignacio, Caroline; Porrachia, Magali; Du, Pinyi; Smith, Davey M; Chaillon, Antoine title: No Evidence of SARS-CoV-2 Seminal Shedding Despite SARS-CoV-2 Persistence in the Upper Respiratory Tract date: 2020-08-07 journal: Open Forum Infect Dis DOI: 10.1093/ofid/ofaa325 sha: doc_id: 350557 cord_uid: 7i7122zi file: cache/cord-350352-wgppovfx.json key: cord-350352-wgppovfx authors: Temmam, Sarah; Barbarino, Alix; Maso, Djérène; Behillil, Sylvie; Enouf, Vincent; Huon, Christèle; Jaraud, Ambre; Chevallier, Lucie; Backovic, Marija; Pérot, Philippe; Verwaerde, Patrick; Tiret, Laurent; van der Werf, Sylvie; Eloit, Marc title: Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus date: 2020-08-29 journal: One Health DOI: 10.1016/j.onehlt.2020.100164 sha: doc_id: 350352 cord_uid: wgppovfx file: cache/cord-350737-nrtrhq1f.json key: cord-350737-nrtrhq1f authors: Chen, Xinchun; Zhou, Boping; Li, Meizhong; Liang, Xiaorong; Wang, Huosheng; Yang, Guilin; Wang, Hui; Le, Xiaohua title: Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome date: 2004-04-01 journal: J Infect Dis DOI: 10.1086/380397 sha: doc_id: 350737 cord_uid: nrtrhq1f file: cache/cord-350855-gofzhff7.json key: cord-350855-gofzhff7 authors: Hou, Yixuan J.; Okuda, Kenichi; Edwards, Caitlin E.; Martinez, David R.; Asakura, Takanori; Dinnon, Kenneth H.; Kato, Takafumi; Lee, Rhianna E.; Yount, Boyd L.; Mascenik, Teresa M.; Chen, Gang; Olivier, Kenneth N.; Ghio, Andrew; Tse, Longping V.; Leist, Sarah R.; Gralinski, Lisa E.; Schäfer, Alexandra; Dang, Hong; Gilmore, Rodney; Nakano, Satoko; Sun, Ling; Fulcher, M. Leslie; Livraghi-Butrico, Alessandra; Nicely, Nathan I.; Cameron, Mark; Cameron, Cheryl; Kelvin, David J.; de Silva, Aravinda; Margolis, David M.; Markmann, Alena; Bartelt, Luther; Zumwalt, Ross; Martinez, Fernando J.; Salvatore, Steven P.; Borczuk, Alain; Tata, Purushothama R.; Sontake, Vishwaraj; Kimple, Adam; Jaspers, Ilona; O’Neal, Wanda K.; Randell, Scott H.; Boucher, Richard C.; Baric, Ralph S. title: SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract date: 2020-05-27 journal: Cell DOI: 10.1016/j.cell.2020.05.042 sha: doc_id: 350855 cord_uid: gofzhff7 file: cache/cord-347351-emdj66vj.json key: cord-347351-emdj66vj authors: Kampf, Günter; Brüggemann, Yannick; Kaba, Hani E.J.; Steinmann, Joerg; Pfaender, Stephanie; Scheithauer, Simone; Steinmann, Eike title: Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 date: 2020-09-18 journal: J Hosp Infect DOI: 10.1016/j.jhin.2020.09.022 sha: doc_id: 347351 cord_uid: emdj66vj file: cache/cord-349659-6drnriun.json key: cord-349659-6drnriun authors: Grant, Benjamin D.; Anderson, Caitlin E.; Williford, John R.; Alonzo, Luis F.; Glukhova, Veronika A.; Boyle, David S.; Weigl, Bernhard H.; Nichols, Kevin P. title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents date: 2020-07-01 journal: Anal Chem DOI: 10.1021/acs.analchem.0c01975 sha: doc_id: 349659 cord_uid: 6drnriun file: cache/cord-349262-gnqbyc6t.json key: cord-349262-gnqbyc6t authors: Hemida, Maged Gomaa; Ali, Mohammed; Alhammadi, Mohammed; Alnaeem, Abdelmohsen title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) date: 2020-10-14 journal: Epidemiol Infect DOI: 10.1017/s0950268820002459 sha: doc_id: 349262 cord_uid: gnqbyc6t file: cache/cord-346539-kxnrf5g5.json key: cord-346539-kxnrf5g5 authors: Riggioni, Carmen; Comberiati, Pasquale; Giovannini, Mattia; Agache, Ioana; Akdis, Mübeccel; Alves‐Correia, Magna; Antó, Josep M.; Arcolaci, Alessandra; Kursat Azkur, Ahmet; Azkur, Dilek; Beken, Burcin; Boccabella, Cristina; Bousquet, Jean; Breiteneder, Heimo; Carvalho, Daniela; De las Vecillas, Leticia; Diamant, Zuzana; Eguiluz‐Gracia, Ibon; Eiwegger, Thomas; Eyerich, Stefanie; Fokkens, Wytske; Gao, Ya‐dong; Hannachi, Farah; Johnston, Sebastian L.; Jutel, Marek; Karavelia, Aspasia; Klimek, Ludger; Moya, Beatriz; Nadeau, Kari; O'Hehir, Robyn; O'Mahony, Liam; Pfaar, Oliver; Sanak, Marek; Schwarze, Jürgen; Sokolowska, Milena; Torres, María J.; van de Veen, Willem; van Zelm, Menno C.; Wang, De Yun; Zhang, Luo; Jiménez‐Saiz, Rodrigo; Akdis, Cezmi A. title: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 date: 2020-06-14 journal: Allergy DOI: 10.1111/all.14449 sha: doc_id: 346539 cord_uid: kxnrf5g5 file: cache/cord-347734-0z2kin6r.json key: cord-347734-0z2kin6r authors: Armann, J. P.; Unrath, M.; Kirsten, C.; Lueck, C.; Dalpke, A.; Berner, R. title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates date: 2020-07-17 journal: nan DOI: 10.1101/2020.07.16.20155143 sha: doc_id: 347734 cord_uid: 0z2kin6r file: cache/cord-353209-qkhfp66l.json key: cord-353209-qkhfp66l authors: Steiner, Daniel J.; Cognetti, John S.; Luta, Ethan P.; Klose, Alanna M.; Bucukovski, Joseph; Bryan, Michael R.; Schmuke, Jon J.; Nguyen-Contant, Phuong; Sangster, Mark Y.; Topham, David J.; Miller, Benjamin L. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.153064 sha: doc_id: 353209 cord_uid: qkhfp66l file: cache/cord-351169-y91fdf66.json key: cord-351169-y91fdf66 authors: Phillips, Lia; Pavisic, Jovana; Kaur, Dominder; Dorrello, N. Valerio; Broglie, Larisa; Hijiya, Nobuko title: Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia date: 2020-09-14 journal: Blood Adv DOI: 10.1182/bloodadvances.2020002745 sha: doc_id: 351169 cord_uid: y91fdf66 file: cache/cord-351649-87g7g5au.json key: cord-351649-87g7g5au authors: Haagmans, Bart L.; Osterhaus, Albert D.M.E. title: SARS date: 2009-01-30 journal: Vaccines for Biodefense and Emerging and Neglected Diseases DOI: 10.1016/b978-0-12-369408-9.00036-6 sha: doc_id: 351649 cord_uid: 87g7g5au file: cache/cord-350992-l6l24pco.json key: cord-350992-l6l24pco authors: Roldan, Eugenia Quiros; Biasiotto, Giorgio; Magro, Paola; Zanella, Isabella title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? date: 2020-05-13 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.104904 sha: doc_id: 350992 cord_uid: l6l24pco file: cache/cord-350959-bsbz3a1l.json key: cord-350959-bsbz3a1l authors: Dovey, Zachary; Mohamed, Nihal; Gharib, Yasmine; Ratnani, Parita; Hammouda, Nada; Nair, Sujit; Chakravarty, Dimple; Stanislaw, Sobotka; Lantz, Anna; Wiklund, Peter; Kyprianou, Natasha; Tewari, Ash title: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists date: 2020-06-16 journal: nan DOI: 10.1016/j.euros.2020.05.005 sha: doc_id: 350959 cord_uid: bsbz3a1l file: cache/cord-352562-qfb478sf.json key: cord-352562-qfb478sf authors: Yamamoto, Lidia; dos Santos, Emilly Henrique; Pinto, Lacyane Silva; Rocha, Mussya Cisotto; Kanunfre, Kelly Aparecida; Vallada, Marcelo Genofre; Okay, Thelma Suely title: SARS-CoV-2 infections with emphasis on pediatric patients: a narrative review date: 2020-09-04 journal: Revista do Instituto de Medicina Tropical de Sao Paulo DOI: 10.1590/s1678-9946202062065 sha: doc_id: 352562 cord_uid: qfb478sf file: cache/cord-350451-lf27iuwk.json key: cord-350451-lf27iuwk authors: Benedetti, Francesca; Pachetti, Maria; Marini, Bruna; Ippodrino, Rudy; Ciccozzi, Massimo; Zella, Davide title: SARS‐CoV‐2: March toward adaptation date: 2020-07-11 journal: J Med Virol DOI: 10.1002/jmv.26233 sha: doc_id: 350451 cord_uid: lf27iuwk file: cache/cord-352909-s11tpfoq.json key: cord-352909-s11tpfoq authors: Sun, Zhiping; Cai, Xia; Gu, Chenjian; Zhang, Rong; Han, Wendong; Qian, Yun; Wang, Yuyan; Xu, Wei; Wu, Yang; Cheng, Xunjia; Yuan, Zhenghong; Xie, Youhua; Qu, Di title: Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions date: 2020-08-14 journal: Cell Discov DOI: 10.1038/s41421-020-00191-9 sha: doc_id: 352909 cord_uid: s11tpfoq file: cache/cord-353524-3w970ycx.json key: cord-353524-3w970ycx authors: Dömling, Alexander; Gao, Li title: Chemistry and Biology of SARS-CoV-2 date: 2020-05-22 journal: Chem DOI: 10.1016/j.chempr.2020.04.023 sha: doc_id: 353524 cord_uid: 3w970ycx file: cache/cord-352123-0bflqj1c.json key: cord-352123-0bflqj1c authors: Csiszar, Anna; Jakab, Ferenc; Valencak, Teresa G.; Lanszki, Zsófia; Tóth, Gábor Endre; Kemenesi, Gábor; Tarantini, Stefano; Fazekas-Pongor, Vince; Ungvari, Zoltan title: Companion animals likely do not spread COVID-19 but may get infected themselves date: 2020-08-07 journal: GeroScience DOI: 10.1007/s11357-020-00248-3 sha: doc_id: 352123 cord_uid: 0bflqj1c file: cache/cord-351011-v4zmksio.json key: cord-351011-v4zmksio authors: Golden, Joseph W.; Cline, Curtis R.; Zeng, Xiankun; Garrison, Aura R.; Carey, Brian D.; Mucker, Eric M.; White, Lauren E.; Shamblin, Joshua D.; Brocato, Rebecca L.; Liu, Jun; Babka, April M.; Rauch, Hypaitia B.; Smith, Jeffrey M.; Hollidge, Bradley S.; Fitzpatrick, Collin; Badger, Catherine V.; Hooper, Jay W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 journal: bioRxiv DOI: 10.1101/2020.07.09.195230 sha: doc_id: 351011 cord_uid: v4zmksio file: cache/cord-353293-vjdwh19x.json key: cord-353293-vjdwh19x authors: nan title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach date: 2020-06-11 journal: Aging Clin Exp Res DOI: 10.1007/s40520-020-01616-x sha: doc_id: 353293 cord_uid: vjdwh19x file: cache/cord-354398-f3cg8gi1.json key: cord-354398-f3cg8gi1 authors: Al-Saud, Haya; Al-Romaih, Khaldoun; Bakheet, Razan; Mahmoud, Lina; Al-Harbi, Najla; Alshareef, Ibtihaj; Judia, Sara Bin; Aharbi, Layla; Alzayed, Abdulaziz; Jabaan, Amjad; Alhadrami, Hani; Albarrag, Ahmed; Azhar, Essam I.; Al-Mozaini, Maha Ahmad title: Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing date: 2020-09-20 journal: Ann Saudi Med DOI: 10.5144/0256-4947.2020.373 sha: doc_id: 354398 cord_uid: f3cg8gi1 file: cache/cord-354597-xubsodnk.json key: cord-354597-xubsodnk authors: Carvalho, Alexandre; Alqusairi, Rana; Adams, Anna; Paul, Michelle; Kothari, Neelay; Peters, Stevany; DeBenedet, Anthony T. title: SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease date: 2020-04-17 journal: Am J Gastroenterol DOI: 10.14309/ajg.0000000000000667 sha: doc_id: 354597 cord_uid: xubsodnk file: cache/cord-351525-306syrrn.json key: cord-351525-306syrrn authors: Yang, Yong-Le; Qin, Pan; Wang, Bin; Liu, Yan; Xu, Guo-Han; Peng, Lei; Zhou, Jiyong; Zhu, Shu Jeffrey; Huang, Yao-Wei title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission date: 2019-11-26 journal: J Virol DOI: 10.1128/jvi.01448-19 sha: doc_id: 351525 cord_uid: 306syrrn file: cache/cord-354394-zojhdnlu.json key: cord-354394-zojhdnlu authors: Wang, Wei-Kung; Chen, Shey-Ying; Liu, I-Jung; Chen, Yee-Chun; Chen, Hui-Ling; Yang, Chao-Fu; Chen, Pei-Jer; Yeh, Shiou-Hwei; Kao, Chuan-Liang; Huang, Li-Min; Hsueh, Po-Ren; Wang, Jann-Tay; Sheng, Wang-Hwei; Fang, Chi-Tai; Hung, Chien-Ching; Hsieh, Szu-Min; Su, Chan-Ping; Chiang, Wen-Chu; Yang, Jyh-Yuan; Lin, Jih-Hui; Hsieh, Szu-Chia; Hu, Hsien-Ping; Chiang, Yu-Ping; Wang, Jin-Town; Yang, Pan-Chyr; Chang, Shan-Chwen title: Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis date: 2004-07-17 journal: Emerg Infect Dis DOI: 10.3201/eid1007.031113 sha: doc_id: 354394 cord_uid: zojhdnlu file: cache/cord-356166-fpno9zg5.json key: cord-356166-fpno9zg5 authors: Miyakawa, Kei; Jeremiah, Sundararaj Stanleyraj; Ohtake, Norihisa; Matsunaga, Satoko; Yamaoka, Yutaro; Nishi, Mayuko; Morita, Takeshi; Saji, Ryo; Nishii, Mototsugu; Kimura, Hirokazu; Hasegawa, Hideki; Takeuchi, Ichiro; Ryo, Akihide title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles date: 2020-09-15 journal: J Mol Cell Biol DOI: 10.1093/jmcb/mjaa047 sha: doc_id: 356166 cord_uid: fpno9zg5 file: cache/cord-351115-dy81dtnk.json key: cord-351115-dy81dtnk authors: Wang, Chen; Konecki, Daniel M.; Marciano, David C.; Govindarajan, Harikumar; Williams, Amanda M.; Wastuwidyaningtyas, Brigitta; Bourquard, Thomas; Katsonis, Panagiotis; Lichtarge, Olivier title: Identification of evolutionarily stable sites across the SARS-CoV-2 proteome date: 2020-10-20 journal: Res Sq DOI: 10.21203/rs.3.rs-95030/v1 sha: doc_id: 351115 cord_uid: dy81dtnk file: cache/cord-353777-t8q99tlq.json key: cord-353777-t8q99tlq authors: Jia, Yong; Shen, Gangxu; Zhang, Yujuan; Huang, Keng-Shiang; Ho, Hsing-Ying; Hor, Wei-Shio; Yang, Chih-Hui; Li, Chengdao; Wang, Wei-Lung title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.09.034942 sha: doc_id: 353777 cord_uid: t8q99tlq file: cache/cord-353704-lfndq85x.json key: cord-353704-lfndq85x authors: Ye, Zi-Wei; Yuan, Shuofeng; Yuen, Kit-San; Fung, Sin-Yee; Chan, Chi-Ping; Jin, Dong-Yan title: Zoonotic origins of human coronaviruses date: 2020-03-15 journal: Int J Biol Sci DOI: 10.7150/ijbs.45472 sha: doc_id: 353704 cord_uid: lfndq85x file: cache/cord-353826-owoec2ud.json key: cord-353826-owoec2ud authors: Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij-Rammerstorfer, Sandra; Wright, Daniel; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W. P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valerie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 journal: NPJ Vaccines DOI: 10.1038/s41541-020-00221-3 sha: doc_id: 353826 cord_uid: owoec2ud file: cache/cord-355567-60sfv60p.json key: cord-355567-60sfv60p authors: Azuma, Kenichi; Yanagi, U; Kagi, Naoki; Kim, Hoon; Ogata, Masayuki; Hayashi, Motoya title: Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control date: 2020-11-03 journal: Environ Health Prev Med DOI: 10.1186/s12199-020-00904-2 sha: doc_id: 355567 cord_uid: 60sfv60p file: cache/cord-353484-q7d0ysbo.json key: cord-353484-q7d0ysbo authors: Liu, Xue; Liu, Chao; Liu, Gang; Luo, Wenxin; Xia, Ningshao title: COVID-19: Progress in diagnostics, therapy and vaccination date: 2020-06-19 journal: Theranostics DOI: 10.7150/thno.47987 sha: doc_id: 353484 cord_uid: q7d0ysbo file: cache/cord-352230-8mazd3eu.json key: cord-352230-8mazd3eu authors: Beeraka, Narasimha M.; Sadhu, Surya P.; Madhunapantula, SubbaRao V.; Rao Pragada, Rajeswara; Svistunov, Andrey A.; Nikolenko, Vladimir N.; Mikhaleva, Liudmila M.; Aliev, Gjumrakch title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 journal: Front Immunol DOI: 10.3389/fimmu.2020.552925 sha: doc_id: 352230 cord_uid: 8mazd3eu file: cache/cord-353392-rqeultbq.json key: cord-353392-rqeultbq authors: Kumar, Govindarajan Venkat; Jeyanthi, Venkadapathi; Ramakrishnan, Saminathan title: A short review on antibody therapy for COVID-19 date: 2020-04-20 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2020.100682 sha: doc_id: 353392 cord_uid: rqeultbq file: cache/cord-354824-7fdcu2f0.json key: cord-354824-7fdcu2f0 authors: Wu, Renyi; Wang, Lujing; Kuo, Hsiao-Chen Dina; Shannar, Ahmad; Peter, Rebecca; Chou, Pochung Jordan; Li, Shanyi; Hudlikar, Rasika; Liu, Xia; Liu, Zhigang; Poiani, George J.; Amorosa, Louis; Brunetti, Luigi; Kong, Ah-Ng title: An Update on Current Therapeutic Drugs Treating COVID-19 date: 2020-05-11 journal: Curr Pharmacol Rep DOI: 10.1007/s40495-020-00216-7 sha: doc_id: 354824 cord_uid: 7fdcu2f0 file: cache/cord-356009-emn2w8if.json key: cord-356009-emn2w8if authors: Roshandel, M. R.; Nateqi, M.; Lak, R.; Aavani, P.; Sari Motlagh, R.; Aghaei Badr, T.; Sfakianos, J.; Kaplan, S. A.; Shariat, S.; Tewari, A. K. title: What Specimen Urologists Should Be Most Concerned About ? A Systematic Review and Meta-Analysis date: 2020-10-13 journal: nan DOI: 10.1101/2020.10.08.20209544 sha: doc_id: 356009 cord_uid: emn2w8if file: cache/cord-350903-nwagvvc5.json key: cord-350903-nwagvvc5 authors: Softic, Laurent; Brillet, Rozenn; Berry, François; Ahnou, Nazim; Nevers, Quentin; Morin-Dewaele, Margot; Hamadat, Sabah; Bruscella, Patrice; Fourati, Slim; Pawlotsky, Jean-Michel; Ahmed-Belkacem, Abdelhakim title: Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025) date: 2020-06-23 journal: Antimicrob Agents Chemother DOI: 10.1128/aac.00876-20 sha: doc_id: 350903 cord_uid: nwagvvc5 Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-cov-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61860 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62824 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62653 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63234 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63307 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63168 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62986 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63236 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63050 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63314 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63437 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63239 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63272 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63326 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63392 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63133 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63140 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61833 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63113 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60910 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-258881-74aijckl author: Wang, Maomao title: Case Report: One Case of Coronavirus Desease 2019(COVID-19) in Patient Co-nfected by HIV With a Low CD4+ T Cell Count date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-258881-74aijckl.txt cache: ./cache/cord-258881-74aijckl.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-258881-74aijckl.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63404 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-009476-4emc4o6n author: Madani, Tariq A title: Case definition and management of patients with MERS coronavirus in Saudi Arabia date: 2014-09-22 pages: extension: .txt txt: ./txt/cord-009476-4emc4o6n.txt cache: ./cache/cord-009476-4emc4o6n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-009476-4emc4o6n.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-255552-k1retwa4 author: Gassen, Nils C. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-255552-k1retwa4.txt cache: ./cache/cord-255552-k1retwa4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255552-k1retwa4.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-265322-3854ddb9 author: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-265322-3854ddb9.txt cache: ./cache/cord-265322-3854ddb9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-265322-3854ddb9.txt' === file2bib.sh === id: cord-258268-7ypq0t3d author: Zanin, Luca title: SARS-CoV-2 can induce brain and spine demyelinating lesions date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-258268-7ypq0t3d.txt cache: ./cache/cord-258268-7ypq0t3d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258268-7ypq0t3d.txt' === file2bib.sh === id: cord-261718-zqoggwnk author: Pietschmann, Jan title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 pages: extension: .txt txt: ./txt/cord-261718-zqoggwnk.txt cache: ./cache/cord-261718-zqoggwnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261718-zqoggwnk.txt' === file2bib.sh === id: cord-256217-fnjer0e0 author: Neri, Piergiorgio title: COVID-19 and the eye immunity: lesson learned from the past and possible new therapeutic insights date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-256217-fnjer0e0.txt cache: ./cache/cord-256217-fnjer0e0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256217-fnjer0e0.txt' === file2bib.sh === id: cord-024133-zv0ysi8m author: Saxena, Shailendra K. title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-024133-zv0ysi8m.txt cache: ./cache/cord-024133-zv0ysi8m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-024133-zv0ysi8m.txt' === file2bib.sh === id: cord-032222-i6gfp4me author: Xue, Ling title: A quick look at the latest developments in the COVID-19 pandemic date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-032222-i6gfp4me.txt cache: ./cache/cord-032222-i6gfp4me.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-032222-i6gfp4me.txt' === file2bib.sh === id: cord-031289-uxoz0xhk author: Coccolini, Federico title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients date: 2020-05-18 pages: extension: .txt txt: ./txt/cord-031289-uxoz0xhk.txt cache: ./cache/cord-031289-uxoz0xhk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-031289-uxoz0xhk.txt' === file2bib.sh === id: cord-253457-gawn4s9g author: Yau, Kevin title: COVID-19 Outbreak in an Urban Hemodialysis Unit date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-253457-gawn4s9g.txt cache: ./cache/cord-253457-gawn4s9g.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-253457-gawn4s9g.txt' === file2bib.sh === id: cord-258914-g6pv8zz9 author: Proud, Pamela C. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-258914-g6pv8zz9.txt cache: ./cache/cord-258914-g6pv8zz9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258914-g6pv8zz9.txt' === file2bib.sh === id: cord-258312-3v5t4k8d author: Majachani, Nicole title: A Case of a Newborn Baby Girl Infected with SARS-CoV-2 Due to Transplacental Viral Transmission date: 2020-10-25 pages: extension: .txt txt: ./txt/cord-258312-3v5t4k8d.txt cache: ./cache/cord-258312-3v5t4k8d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258312-3v5t4k8d.txt' === file2bib.sh === id: cord-265128-i0d4lxko author: Gurung, Arun Bahadur title: Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-265128-i0d4lxko.txt cache: ./cache/cord-265128-i0d4lxko.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265128-i0d4lxko.txt' === file2bib.sh === id: cord-025119-201ac32t author: Salman, Saad title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-025119-201ac32t.txt cache: ./cache/cord-025119-201ac32t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-025119-201ac32t.txt' === file2bib.sh === id: cord-254968-czrgzyr3 author: Zhang, Qiang title: A serological survey of SARS-CoV-2 in cat in Wuhan date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-254968-czrgzyr3.txt cache: ./cache/cord-254968-czrgzyr3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254968-czrgzyr3.txt' === file2bib.sh === id: cord-029813-o2uzcuai author: Rusconi, Stefano title: COVID-19: studying the global pandemic – foreword date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-029813-o2uzcuai.txt cache: ./cache/cord-029813-o2uzcuai.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-029813-o2uzcuai.txt' === file2bib.sh === id: cord-019048-29wzpwvr author: Franks, Teri J. title: Coronavirus date: 2013-08-26 pages: extension: .txt txt: ./txt/cord-019048-29wzpwvr.txt cache: ./cache/cord-019048-29wzpwvr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-019048-29wzpwvr.txt' === file2bib.sh === id: cord-150183-zzzyewjb author: Phillips, J. C. title: Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-150183-zzzyewjb.txt cache: ./cache/cord-150183-zzzyewjb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-150183-zzzyewjb.txt' === file2bib.sh === id: cord-252767-as841xo0 author: Fischer, Bastian title: SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-252767-as841xo0.txt cache: ./cache/cord-252767-as841xo0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252767-as841xo0.txt' === file2bib.sh === id: cord-024317-w1ep0wq8 author: Ku, Zhiqiang title: Antibody therapies for the treatment of COVID-19 date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-024317-w1ep0wq8.txt cache: ./cache/cord-024317-w1ep0wq8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-024317-w1ep0wq8.txt' === file2bib.sh === id: cord-266511-g5h4tazp author: Deslandes, A title: SARS-COV-2 was already spreading in France in late December 2019 date: 2020-05-03 pages: extension: .txt txt: ./txt/cord-266511-g5h4tazp.txt cache: ./cache/cord-266511-g5h4tazp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-266511-g5h4tazp.txt' === file2bib.sh === id: cord-254636-3lr008th author: Shishir, Tushar Ahmed title: In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-254636-3lr008th.txt cache: ./cache/cord-254636-3lr008th.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254636-3lr008th.txt' === file2bib.sh === id: cord-193133-puqcbf8t author: Piplani, Sakshi title: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-193133-puqcbf8t.txt cache: ./cache/cord-193133-puqcbf8t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-193133-puqcbf8t.txt' === file2bib.sh === id: cord-252232-vgq6gjpx author: Hou, Yuxuan title: Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry date: 2010-06-22 pages: extension: .txt txt: ./txt/cord-252232-vgq6gjpx.txt cache: ./cache/cord-252232-vgq6gjpx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252232-vgq6gjpx.txt' === file2bib.sh === id: cord-253905-zknmfgsh author: Li, Xingguang title: Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 date: 2020-03-11 pages: extension: .txt txt: ./txt/cord-253905-zknmfgsh.txt cache: ./cache/cord-253905-zknmfgsh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253905-zknmfgsh.txt' === file2bib.sh === id: cord-034354-4xu97je3 author: Wang, Hongye title: SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-034354-4xu97je3.txt cache: ./cache/cord-034354-4xu97je3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-034354-4xu97je3.txt' === file2bib.sh === id: cord-033780-184e64tr author: Smith, Rasheid title: Implications of current and future approaches to coronavirus disease 2019 testing date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-033780-184e64tr.txt cache: ./cache/cord-033780-184e64tr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-033780-184e64tr.txt' === file2bib.sh === id: cord-214854-ck61ja2t author: Zhong, Jing title: Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-214854-ck61ja2t.txt cache: ./cache/cord-214854-ck61ja2t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-214854-ck61ja2t.txt' === file2bib.sh === id: cord-262276-5nue46dm author: Roussel, Yanis title: SARS-CoV-2: fear versus data date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-262276-5nue46dm.txt cache: ./cache/cord-262276-5nue46dm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262276-5nue46dm.txt' === file2bib.sh === id: cord-257399-p6of5fno author: Gentry, Chris A title: Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-257399-p6of5fno.txt cache: ./cache/cord-257399-p6of5fno.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257399-p6of5fno.txt' === file2bib.sh === id: cord-262328-q7mt0xve author: Wajnberg, Ania title: Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-262328-q7mt0xve.txt cache: ./cache/cord-262328-q7mt0xve.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262328-q7mt0xve.txt' === file2bib.sh === id: cord-033551-eojpkxz9 author: Shekh, Shamasoddin title: In silico allicin induced S-thioallylation of SARS-CoV-2 main protease date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-033551-eojpkxz9.txt cache: ./cache/cord-033551-eojpkxz9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-033551-eojpkxz9.txt' === file2bib.sh === id: cord-252600-bvh1o64r author: Galasiti Kankanamalage, Anushka C. title: Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element date: 2018-04-25 pages: extension: .txt txt: ./txt/cord-252600-bvh1o64r.txt cache: ./cache/cord-252600-bvh1o64r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252600-bvh1o64r.txt' === file2bib.sh === id: cord-255815-5d9bqji0 author: Malik, Ajamaluddin title: MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization date: 2017-05-30 pages: extension: .txt txt: ./txt/cord-255815-5d9bqji0.txt cache: ./cache/cord-255815-5d9bqji0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255815-5d9bqji0.txt' === file2bib.sh === id: cord-261075-wqtxhiy8 author: Zhang, Meng title: The nervous system——a new territory being explored of SARS-CoV-2 date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-261075-wqtxhiy8.txt cache: ./cache/cord-261075-wqtxhiy8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261075-wqtxhiy8.txt' === file2bib.sh === id: cord-015503-j99cgsjt author: Tang, Xiaolu title: On the origin and continuing evolution of SARS-CoV-2 date: 2020-03-03 pages: extension: .txt txt: ./txt/cord-015503-j99cgsjt.txt cache: ./cache/cord-015503-j99cgsjt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015503-j99cgsjt.txt' === file2bib.sh === id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-255997-oer5lxxr.txt cache: ./cache/cord-255997-oer5lxxr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255997-oer5lxxr.txt' === file2bib.sh === id: cord-266348-tbr2ynx0 author: Stroemer, A. title: Diagnostic accuracy of six commercial SARS-CoV-2 IgG/total antibody assays and identification of SARS-CoV-2 neutralizing antibodies in convalescent sera date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-266348-tbr2ynx0.txt cache: ./cache/cord-266348-tbr2ynx0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-266348-tbr2ynx0.txt' === file2bib.sh === id: cord-262266-m0fjt483 author: Peddu, Vikas title: Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-262266-m0fjt483.txt cache: ./cache/cord-262266-m0fjt483.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262266-m0fjt483.txt' === file2bib.sh === id: cord-254469-7q6xi2xx author: Wang, Fuzhou title: An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-254469-7q6xi2xx.txt cache: ./cache/cord-254469-7q6xi2xx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254469-7q6xi2xx.txt' === file2bib.sh === id: cord-265366-vmuqbpkk author: Leibowitz, Jill title: Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without SARS-CoV-2 Infection date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-265366-vmuqbpkk.txt cache: ./cache/cord-265366-vmuqbpkk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-265366-vmuqbpkk.txt' === file2bib.sh === id: cord-254395-tu4aqczj author: Froggatt, Heather M. title: Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CL(pro) Reporter Assay date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-254395-tu4aqczj.txt cache: ./cache/cord-254395-tu4aqczj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254395-tu4aqczj.txt' === file2bib.sh === id: cord-262045-r2iqpmmc author: Smits, Saskia L. title: Reliable typing of MERS-CoV variants with a small genome fragment date: 2014-12-15 pages: extension: .txt txt: ./txt/cord-262045-r2iqpmmc.txt cache: ./cache/cord-262045-r2iqpmmc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262045-r2iqpmmc.txt' === file2bib.sh === id: cord-256146-d599uera author: Kuiken, Thijs title: Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome date: 2003-07-26 pages: extension: .txt txt: ./txt/cord-256146-d599uera.txt cache: ./cache/cord-256146-d599uera.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256146-d599uera.txt' === file2bib.sh === id: cord-032751-pmclolvh author: Head, Katharine J. title: A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-032751-pmclolvh.txt cache: ./cache/cord-032751-pmclolvh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-032751-pmclolvh.txt' === file2bib.sh === id: cord-256888-tdx12ccj author: Bradley, Benjamin T title: Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-256888-tdx12ccj.txt cache: ./cache/cord-256888-tdx12ccj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256888-tdx12ccj.txt' === file2bib.sh === id: cord-257105-vrwuaknf author: Davies, Julie title: Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19 date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-257105-vrwuaknf.txt cache: ./cache/cord-257105-vrwuaknf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257105-vrwuaknf.txt' === file2bib.sh === id: cord-031079-9lxhvyyb author: Chen, Li title: The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-031079-9lxhvyyb.txt cache: ./cache/cord-031079-9lxhvyyb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-031079-9lxhvyyb.txt' === file2bib.sh === id: cord-158628-71n1tgrw author: Russo, Giulia title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-158628-71n1tgrw.txt cache: ./cache/cord-158628-71n1tgrw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-158628-71n1tgrw.txt' === file2bib.sh === id: cord-258595-bk35vxlr author: Westhaus, Sandra title: Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-258595-bk35vxlr.txt cache: ./cache/cord-258595-bk35vxlr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258595-bk35vxlr.txt' === file2bib.sh === id: cord-265329-bsypo08l author: van Dorp, Lucy title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-265329-bsypo08l.txt cache: ./cache/cord-265329-bsypo08l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265329-bsypo08l.txt' === file2bib.sh === id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-264031-0y7xbgun.txt cache: ./cache/cord-264031-0y7xbgun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264031-0y7xbgun.txt' === file2bib.sh === id: cord-263481-w5ytp1q7 author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-263481-w5ytp1q7.txt cache: ./cache/cord-263481-w5ytp1q7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263481-w5ytp1q7.txt' === file2bib.sh === id: cord-252456-971d0sir author: Hemida, Maged Gomaa title: The SARS-CoV-2 outbreak from a one health perspective date: 2020-03-16 pages: extension: .txt txt: ./txt/cord-252456-971d0sir.txt cache: ./cache/cord-252456-971d0sir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252456-971d0sir.txt' === file2bib.sh === id: cord-193489-u6ewlh16 author: Wang, Rui title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-193489-u6ewlh16.txt cache: ./cache/cord-193489-u6ewlh16.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-193489-u6ewlh16.txt' === file2bib.sh === id: cord-255883-mz6nyisw author: Asif, Muhammad title: COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-255883-mz6nyisw.txt cache: ./cache/cord-255883-mz6nyisw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255883-mz6nyisw.txt' === file2bib.sh === id: cord-257958-yehnlabq author: Barh, Debmalya title: Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19 date: 2020-10-10 pages: extension: .txt txt: ./txt/cord-257958-yehnlabq.txt cache: ./cache/cord-257958-yehnlabq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257958-yehnlabq.txt' === file2bib.sh === id: cord-124012-5zxkd2jy author: Schwab, Patrick title: predCOVID-19: A Systematic Study of Clinical Predictive Models for Coronavirus Disease 2019 date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-124012-5zxkd2jy.txt cache: ./cache/cord-124012-5zxkd2jy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-124012-5zxkd2jy.txt' === file2bib.sh === id: cord-252389-xrdbmosj author: Kumar, Mukesh title: Neurological manifestations and comorbidity associated with COVID-19: an overview date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-252389-xrdbmosj.txt cache: ./cache/cord-252389-xrdbmosj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252389-xrdbmosj.txt' === file2bib.sh === id: cord-029547-9ei1ram3 author: Li, Jingwei title: The epidemiology and therapeutic options for the COVID-19 date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-029547-9ei1ram3.txt cache: ./cache/cord-029547-9ei1ram3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-029547-9ei1ram3.txt' === file2bib.sh === id: cord-030934-t7akdu6x author: Bahrami, Afsane title: Genetic and pathogenic characterization of SARS-CoV-2: a review date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-030934-t7akdu6x.txt cache: ./cache/cord-030934-t7akdu6x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-030934-t7akdu6x.txt' === file2bib.sh === id: cord-254446-yxqbe1dj author: Ren, Yunzhao R. title: A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19 date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-254446-yxqbe1dj.txt cache: ./cache/cord-254446-yxqbe1dj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254446-yxqbe1dj.txt' === file2bib.sh === id: cord-253844-y6xdcf20 author: Yesudhas, Dhanusha title: COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-253844-y6xdcf20.txt cache: ./cache/cord-253844-y6xdcf20.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253844-y6xdcf20.txt' === file2bib.sh === id: cord-253665-1dn3ek34 author: Vishnubalaji, Radhakrishnan title: Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-253665-1dn3ek34.txt cache: ./cache/cord-253665-1dn3ek34.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253665-1dn3ek34.txt' === file2bib.sh === id: cord-260729-b12v3c8c author: de Lang, Anna title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date: 2007-08-10 pages: extension: .txt txt: ./txt/cord-260729-b12v3c8c.txt cache: ./cache/cord-260729-b12v3c8c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-260729-b12v3c8c.txt' === file2bib.sh === id: cord-268476-3lxsh1zz author: Skoog, Hunter title: Tracheotomy in the SARS‐CoV‐2 pandemic date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-268476-3lxsh1zz.txt cache: ./cache/cord-268476-3lxsh1zz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-268476-3lxsh1zz.txt' === file2bib.sh === id: cord-264267-weat0qs6 author: Kleine-Weber, Hannah title: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus date: 2020-01-21 pages: extension: .txt txt: ./txt/cord-264267-weat0qs6.txt cache: ./cache/cord-264267-weat0qs6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264267-weat0qs6.txt' === file2bib.sh === id: cord-268034-7id7sfsu author: Auerswald, Heidi title: Assessment of Inactivation Procedures for SARS-CoV-2 date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-268034-7id7sfsu.txt cache: ./cache/cord-268034-7id7sfsu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-268034-7id7sfsu.txt' === file2bib.sh === id: cord-104500-m0kfom0x author: Kyriakopoulos, Anthony M. title: The Potential Role of Super Spread Events in SARS-COV-2 Pandemic; a Narrative Review date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-104500-m0kfom0x.txt cache: ./cache/cord-104500-m0kfom0x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-104500-m0kfom0x.txt' === file2bib.sh === id: cord-267887-ntwvquqz author: Yang, Ren title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-267887-ntwvquqz.txt cache: ./cache/cord-267887-ntwvquqz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-267887-ntwvquqz.txt' === file2bib.sh === id: cord-256020-wrui3i2l author: Fadaka, Adewale Oluwaseun title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-256020-wrui3i2l.txt cache: ./cache/cord-256020-wrui3i2l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256020-wrui3i2l.txt' === file2bib.sh === id: cord-256508-ce59ovan author: Asselah, Tarik title: COVID-19: discovery, diagnostics and drug development date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-256508-ce59ovan.txt cache: ./cache/cord-256508-ce59ovan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256508-ce59ovan.txt' === file2bib.sh === id: cord-256737-ptjng78b author: McBride, Corrin E. title: Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein date: 2010-09-01 pages: extension: .txt txt: ./txt/cord-256737-ptjng78b.txt cache: ./cache/cord-256737-ptjng78b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256737-ptjng78b.txt' === file2bib.sh === id: cord-268388-kkhuzf3p author: Sharif-Yakan, Ahmad title: Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date: 2014-12-04 pages: extension: .txt txt: ./txt/cord-268388-kkhuzf3p.txt cache: ./cache/cord-268388-kkhuzf3p.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268388-kkhuzf3p.txt' === file2bib.sh === id: cord-270533-s2d3q4ob author: Lau, Yu-Lung title: SARS: future research and vaccine date: 2004-11-05 pages: extension: .txt txt: ./txt/cord-270533-s2d3q4ob.txt cache: ./cache/cord-270533-s2d3q4ob.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-270533-s2d3q4ob.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75374 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73880 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75874 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 76156 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75866 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75389 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-271243-8cfyen86 author: Xiao, Y. title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus date: 2008-05-31 pages: extension: .txt txt: ./txt/cord-271243-8cfyen86.txt cache: ./cache/cord-271243-8cfyen86.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271243-8cfyen86.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-268468-036i1082 author: Asif, Muhammad title: The role of biosensors in COVID-19 outbreak date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-268468-036i1082.txt cache: ./cache/cord-268468-036i1082.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268468-036i1082.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-270396-3bcnnyfq author: Karacin, Cengiz title: How does COVID-19 fear and anxiety affect chemotherapy adherence in patients with cancer date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-270396-3bcnnyfq.txt cache: ./cache/cord-270396-3bcnnyfq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270396-3bcnnyfq.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-270116-r2rnnsfh author: Lippi, Giuseppe title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-270116-r2rnnsfh.txt cache: ./cache/cord-270116-r2rnnsfh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270116-r2rnnsfh.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-269275-b7xxk48t author: Tang, Xiaojia title: Neurological manifestations in COVID-19 and its possible mechanism date: 2020-09-27 pages: extension: .txt txt: ./txt/cord-269275-b7xxk48t.txt cache: ./cache/cord-269275-b7xxk48t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269275-b7xxk48t.txt' === file2bib.sh === id: cord-278522-e4qa19o6 author: Park, Se Yoon title: Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-278522-e4qa19o6.txt cache: ./cache/cord-278522-e4qa19o6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-278522-e4qa19o6.txt' === file2bib.sh === id: cord-275454-an8xvow3 author: Clark, Andrew E title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Screening With Specimen Pools: Time to Swim, or Too Deep for Comfort? date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-275454-an8xvow3.txt cache: ./cache/cord-275454-an8xvow3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-275454-an8xvow3.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 78446 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-272010-kc0gi3cj author: Anand, Sai Priya title: Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-272010-kc0gi3cj.txt cache: ./cache/cord-272010-kc0gi3cj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272010-kc0gi3cj.txt' === file2bib.sh === id: cord-275138-033r259v author: Hayden, Frederick G title: Towards improving clinical management of Middle East respiratory syndrome coronavirus infection date: 2014-07-31 pages: extension: .txt txt: ./txt/cord-275138-033r259v.txt cache: ./cache/cord-275138-033r259v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275138-033r259v.txt' === file2bib.sh === id: cord-272603-nbosceoz author: Lin, Qiuyuan title: Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-272603-nbosceoz.txt cache: ./cache/cord-272603-nbosceoz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272603-nbosceoz.txt' === file2bib.sh === id: cord-274399-cd7cmpoj author: Barzin, Amir title: SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-274399-cd7cmpoj.txt cache: ./cache/cord-274399-cd7cmpoj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-274399-cd7cmpoj.txt' === file2bib.sh === id: cord-273451-xnce010o author: Salisbury-Afshar, Elizabeth M. title: Vulnerable Populations: Weathering the Pandemic Storm date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-273451-xnce010o.txt cache: ./cache/cord-273451-xnce010o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273451-xnce010o.txt' === file2bib.sh === id: cord-271781-cfv0ta10 author: Patel, Kishan P. title: Transmission of SARS-CoV-2: an update of current literature date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-271781-cfv0ta10.txt cache: ./cache/cord-271781-cfv0ta10.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271781-cfv0ta10.txt' === file2bib.sh === id: cord-278618-7tu5c7m1 author: Romano-Bertrand, Sara title: Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission? date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-278618-7tu5c7m1.txt cache: ./cache/cord-278618-7tu5c7m1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278618-7tu5c7m1.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-269289-6uog10j4 author: Mabillard, Holly title: Electrolyte Disturbances in SARS-CoV-2 Infection date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-269289-6uog10j4.txt cache: ./cache/cord-269289-6uog10j4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-269289-6uog10j4.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-270550-if748w2n author: Bailey, Adam L. title: SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-270550-if748w2n.txt cache: ./cache/cord-270550-if748w2n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270550-if748w2n.txt' === file2bib.sh === id: cord-252049-rgdynmla author: Tomar, Sakshi title: Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS date: 2015-06-08 pages: extension: .txt txt: ./txt/cord-252049-rgdynmla.txt cache: ./cache/cord-252049-rgdynmla.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252049-rgdynmla.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-268718-tt07cwrf author: Tan, Heng Wee title: Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-268718-tt07cwrf.txt cache: ./cache/cord-268718-tt07cwrf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268718-tt07cwrf.txt' === file2bib.sh === id: cord-275313-mfyff9ne author: Modjarrad, Kayvon title: Treatment strategies for Middle East respiratory syndrome coronavirus date: 2016-01-01 pages: extension: .txt txt: ./txt/cord-275313-mfyff9ne.txt cache: ./cache/cord-275313-mfyff9ne.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275313-mfyff9ne.txt' === file2bib.sh === id: cord-278370-fuu20ae7 author: Palao, M. title: Multiple Sclerosis following SARS-CoV-2 infection date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-278370-fuu20ae7.txt cache: ./cache/cord-278370-fuu20ae7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278370-fuu20ae7.txt' === file2bib.sh === id: cord-277841-7sp8ftbc author: Kumari, Pratibha title: Potential diagnostics and therapeutic approaches in COVID-19 date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-277841-7sp8ftbc.txt cache: ./cache/cord-277841-7sp8ftbc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277841-7sp8ftbc.txt' === file2bib.sh === id: cord-274122-n9jnu2ah author: Mielech, Anna M. title: MERS-CoV papain-like protease has deISGylating and deubiquitinating activities date: 2014-02-01 pages: extension: .txt txt: ./txt/cord-274122-n9jnu2ah.txt cache: ./cache/cord-274122-n9jnu2ah.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274122-n9jnu2ah.txt' === file2bib.sh === id: cord-284068-sbon3aes author: Mok, Chee Keng title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-284068-sbon3aes.txt cache: ./cache/cord-284068-sbon3aes.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-284068-sbon3aes.txt' === file2bib.sh === id: cord-272113-j82z4q8x author: Akaji, Kenichi title: Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-272113-j82z4q8x.txt cache: ./cache/cord-272113-j82z4q8x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272113-j82z4q8x.txt' === file2bib.sh === id: cord-275565-xerr4vki author: Kumar, Manish title: Decay of SARS-CoV-2 RNA along the wastewater treatment outfitted with Upflow Anaerobic Sludge Blanket (UASB) system evaluated through two sample concentration techniques date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-275565-xerr4vki.txt cache: ./cache/cord-275565-xerr4vki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275565-xerr4vki.txt' === file2bib.sh === id: cord-279940-i2rgjpxf author: Comentale, Giuseppe title: Sars-Cov-2 interference in HEME production: is it the time for an early predictive biomarker? date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-279940-i2rgjpxf.txt cache: ./cache/cord-279940-i2rgjpxf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279940-i2rgjpxf.txt' === file2bib.sh === id: cord-275926-rj23z7po author: Fontanella, Marco M. title: Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-275926-rj23z7po.txt cache: ./cache/cord-275926-rj23z7po.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275926-rj23z7po.txt' === file2bib.sh === id: cord-271505-eot38721 author: Wang, Hongliang title: Molecular pathogenesis of severe acute respiratory syndrome date: 2006-09-28 pages: extension: .txt txt: ./txt/cord-271505-eot38721.txt cache: ./cache/cord-271505-eot38721.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271505-eot38721.txt' === file2bib.sh === id: cord-277253-vy0mvzeb author: Liu, Hongbo title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-277253-vy0mvzeb.txt cache: ./cache/cord-277253-vy0mvzeb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277253-vy0mvzeb.txt' === file2bib.sh === id: cord-280774-r2xm164s author: Gallizzi, Romina title: Management of pernio‐like cutaneous manifestations in children during the outbreak of covid‐19. date: 2020-09-19 pages: extension: .txt txt: ./txt/cord-280774-r2xm164s.txt cache: ./cache/cord-280774-r2xm164s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280774-r2xm164s.txt' === file2bib.sh === id: cord-275252-4e3cn50u author: Rad SM, Ali Hosseini title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 pages: extension: .txt txt: ./txt/cord-275252-4e3cn50u.txt cache: ./cache/cord-275252-4e3cn50u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275252-4e3cn50u.txt' === file2bib.sh === id: cord-276630-qci7khki author: Lima, William Gustavo title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-276630-qci7khki.txt cache: ./cache/cord-276630-qci7khki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276630-qci7khki.txt' === file2bib.sh === id: cord-273182-djb0ozrt author: Díez, José María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-273182-djb0ozrt.txt cache: ./cache/cord-273182-djb0ozrt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273182-djb0ozrt.txt' === file2bib.sh === id: cord-274506-fzcuu4ma author: Jo, Seri title: Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors date: 2019-09-12 pages: extension: .txt txt: ./txt/cord-274506-fzcuu4ma.txt cache: ./cache/cord-274506-fzcuu4ma.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274506-fzcuu4ma.txt' === file2bib.sh === id: cord-274834-24v2b509 author: Lima, Rosiane title: Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-274834-24v2b509.txt cache: ./cache/cord-274834-24v2b509.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274834-24v2b509.txt' === file2bib.sh === id: cord-274396-l611eisi author: Park, Su-Jin title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-274396-l611eisi.txt cache: ./cache/cord-274396-l611eisi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274396-l611eisi.txt' === file2bib.sh === id: cord-284589-j1609xlu author: Sedova, Mayya title: Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-284589-j1609xlu.txt cache: ./cache/cord-284589-j1609xlu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284589-j1609xlu.txt' === file2bib.sh === id: cord-271648-m2c5bvuj author: Ashour, Hossam M. title: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks date: 2020-03-04 pages: extension: .txt txt: ./txt/cord-271648-m2c5bvuj.txt cache: ./cache/cord-271648-m2c5bvuj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271648-m2c5bvuj.txt' === file2bib.sh === id: cord-282338-u01qv3uc author: Cherry, James. D. title: The chronology of the 2002–2003 SARS mini pandemic date: 2004-11-05 pages: extension: .txt txt: ./txt/cord-282338-u01qv3uc.txt cache: ./cache/cord-282338-u01qv3uc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282338-u01qv3uc.txt' === file2bib.sh === id: cord-272654-hh29olk7 author: Bošnjak, Berislav title: Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-272654-hh29olk7.txt cache: ./cache/cord-272654-hh29olk7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-272654-hh29olk7.txt' === file2bib.sh === id: cord-277076-yvsyo4l9 author: Berger, A. title: SARS date: 2019-09-12 pages: extension: .txt txt: ./txt/cord-277076-yvsyo4l9.txt cache: ./cache/cord-277076-yvsyo4l9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277076-yvsyo4l9.txt' === file2bib.sh === id: cord-279443-2e4gz2bo author: Khan, Suliman title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-279443-2e4gz2bo.txt cache: ./cache/cord-279443-2e4gz2bo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279443-2e4gz2bo.txt' === file2bib.sh === id: cord-281679-xmbnpawj author: Meekins, David A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-281679-xmbnpawj.txt cache: ./cache/cord-281679-xmbnpawj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281679-xmbnpawj.txt' === file2bib.sh === id: cord-292025-dr611nse author: Kam, Kai-qian title: Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-292025-dr611nse.txt cache: ./cache/cord-292025-dr611nse.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292025-dr611nse.txt' === file2bib.sh === id: cord-287501-7it4kh0e author: Roh, Changhyun title: A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide date: 2012-05-03 pages: extension: .txt txt: ./txt/cord-287501-7it4kh0e.txt cache: ./cache/cord-287501-7it4kh0e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287501-7it4kh0e.txt' === file2bib.sh === id: cord-268206-ino9srb6 author: Hamed, Manal A. title: An overview on COVID-19: reality and expectation date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-268206-ino9srb6.txt cache: ./cache/cord-268206-ino9srb6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-268206-ino9srb6.txt' === file2bib.sh === id: cord-283966-eln8ljjj author: Meyer, Benjamin title: Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013 date: 2014-04-17 pages: extension: .txt txt: ./txt/cord-283966-eln8ljjj.txt cache: ./cache/cord-283966-eln8ljjj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283966-eln8ljjj.txt' === file2bib.sh === id: cord-275946-ofd2ipvs author: Cheng, Matthew P. title: Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-275946-ofd2ipvs.txt cache: ./cache/cord-275946-ofd2ipvs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275946-ofd2ipvs.txt' === file2bib.sh === id: cord-274841-rcdoewwv author: Tay, Matthew Zirui title: The trinity of COVID-19: immunity, inflammation and intervention date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-274841-rcdoewwv.txt cache: ./cache/cord-274841-rcdoewwv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274841-rcdoewwv.txt' === file2bib.sh === id: cord-282142-76jr4p7n author: Wang, Yun title: Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-282142-76jr4p7n.txt cache: ./cache/cord-282142-76jr4p7n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282142-76jr4p7n.txt' === file2bib.sh === id: cord-283709-y59h5bw8 author: Chan, Renee W Y title: Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study date: 2014-08-28 pages: extension: .txt txt: ./txt/cord-283709-y59h5bw8.txt cache: ./cache/cord-283709-y59h5bw8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283709-y59h5bw8.txt' === file2bib.sh === id: cord-285168-qkadqohe author: Delatorre, Edson title: Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-285168-qkadqohe.txt cache: ./cache/cord-285168-qkadqohe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285168-qkadqohe.txt' === file2bib.sh === id: cord-281684-m3m4mhye author: Fagre, Anna C. title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-281684-m3m4mhye.txt cache: ./cache/cord-281684-m3m4mhye.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281684-m3m4mhye.txt' === file2bib.sh === id: cord-283956-zgrtux7i author: Amin, Sk. Abdul title: Fight against novel coronavirus: A perspective of medicinal chemists date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-283956-zgrtux7i.txt cache: ./cache/cord-283956-zgrtux7i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283956-zgrtux7i.txt' === file2bib.sh === id: cord-277399-0w8is9xm author: Esteves, Sandro C. title: SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-277399-0w8is9xm.txt cache: ./cache/cord-277399-0w8is9xm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-277399-0w8is9xm.txt' === file2bib.sh === id: cord-275690-83nrzfon author: Stanifer, Megan L. title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-275690-83nrzfon.txt cache: ./cache/cord-275690-83nrzfon.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275690-83nrzfon.txt' === file2bib.sh === id: cord-279105-e2zjxjox author: Lee, Cheryl Yi-Pin title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-279105-e2zjxjox.txt cache: ./cache/cord-279105-e2zjxjox.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279105-e2zjxjox.txt' === file2bib.sh === id: cord-280662-gakayv6e author: Bian, Jingwei title: Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-280662-gakayv6e.txt cache: ./cache/cord-280662-gakayv6e.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280662-gakayv6e.txt' === file2bib.sh === id: cord-278362-pwi48i20 author: Khan, Abbas title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-278362-pwi48i20.txt cache: ./cache/cord-278362-pwi48i20.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278362-pwi48i20.txt' === file2bib.sh === id: cord-289716-nleql08z author: Tsitsilonis, Ourania E. title: Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-289716-nleql08z.txt cache: ./cache/cord-289716-nleql08z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-289716-nleql08z.txt' === file2bib.sh === id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-277487-jgbjxgh1.txt cache: ./cache/cord-277487-jgbjxgh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277487-jgbjxgh1.txt' === file2bib.sh === id: cord-284867-p4jgyusp author: Schöler, Lara title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-284867-p4jgyusp.txt cache: ./cache/cord-284867-p4jgyusp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284867-p4jgyusp.txt' === file2bib.sh === id: cord-293688-g6kag5ij author: Nora, Holtmann title: Assessment of SARS-CoV-2 in human semen - a cohort study date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-293688-g6kag5ij.txt cache: ./cache/cord-293688-g6kag5ij.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293688-g6kag5ij.txt' === file2bib.sh === id: cord-281529-2rec51xg author: Haagmans, Bart L title: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation date: 2013-12-17 pages: extension: .txt txt: ./txt/cord-281529-2rec51xg.txt cache: ./cache/cord-281529-2rec51xg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281529-2rec51xg.txt' === file2bib.sh === id: cord-290796-x9xqqcj6 author: Stefanelli, P. title: Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento date: 2020-11-13 pages: extension: .txt txt: ./txt/cord-290796-x9xqqcj6.txt cache: ./cache/cord-290796-x9xqqcj6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290796-x9xqqcj6.txt' === file2bib.sh === id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-262119-s6hc7fxs.txt cache: ./cache/cord-262119-s6hc7fxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262119-s6hc7fxs.txt' === file2bib.sh === id: cord-288731-x2cwyvb7 author: Puenpa, Jiratchaya title: Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-288731-x2cwyvb7.txt cache: ./cache/cord-288731-x2cwyvb7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288731-x2cwyvb7.txt' === file2bib.sh === id: cord-280821-kc0ut4oy author: Venturini, Elisabetta title: Treatment of children with COVID-19: position paper of the Italian Society of Pediatric Infectious Disease date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-280821-kc0ut4oy.txt cache: ./cache/cord-280821-kc0ut4oy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280821-kc0ut4oy.txt' === file2bib.sh === id: cord-287847-rmhvc5n5 author: Miles, Brett A. title: Tracheostomy during SARS‐CoV‐2 pandemic: Recommendations from the New York Head and Neck Society date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-287847-rmhvc5n5.txt cache: ./cache/cord-287847-rmhvc5n5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-287847-rmhvc5n5.txt' === file2bib.sh === id: cord-280068-rszu1c48 author: Twomey, Julianne D. title: COVID-19 update: The race to therapeutic development date: 2020-10-24 pages: extension: .txt txt: ./txt/cord-280068-rszu1c48.txt cache: ./cache/cord-280068-rszu1c48.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280068-rszu1c48.txt' === file2bib.sh === id: cord-289588-n61gz7pi author: Samudrala, Pavan Kumar title: Virology, pathogenesis, diagnosis and in-line treatment of COVID-19 date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-289588-n61gz7pi.txt cache: ./cache/cord-289588-n61gz7pi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-289588-n61gz7pi.txt' === file2bib.sh === id: cord-293082-fw7deem8 author: Zhang, Guangzhi title: Animal coronaviruses and SARS‐CoV‐2 date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-293082-fw7deem8.txt cache: ./cache/cord-293082-fw7deem8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293082-fw7deem8.txt' === file2bib.sh === id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-264814-v4wnmg03.txt cache: ./cache/cord-264814-v4wnmg03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264814-v4wnmg03.txt' === file2bib.sh === id: cord-284498-54j6ys8s author: Ihsanullah, Ihsanullah title: Coronavirus 2 (SARS-CoV-2) in water environments: Current status, challenges and research opportunities date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-284498-54j6ys8s.txt cache: ./cache/cord-284498-54j6ys8s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284498-54j6ys8s.txt' === file2bib.sh === id: cord-289407-8fje16z1 author: Moore, G. title: Detection of SARS-CoV-2 within the healthcare environment: a multicentre study conducted during the first wave of the COVID-19 outbreak in England date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-289407-8fje16z1.txt cache: ./cache/cord-289407-8fje16z1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289407-8fje16z1.txt' === file2bib.sh === id: cord-282058-it0ojdk3 author: Yu, Yuanqiang title: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-282058-it0ojdk3.txt cache: ./cache/cord-282058-it0ojdk3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282058-it0ojdk3.txt' === file2bib.sh === id: cord-268483-joiajgs4 author: Shah, Vibhuti Kumar title: Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-268483-joiajgs4.txt cache: ./cache/cord-268483-joiajgs4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-268483-joiajgs4.txt' === file2bib.sh === id: cord-291523-4dtk1kyh author: Nguyen, Thanh Thi title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-291523-4dtk1kyh.txt cache: ./cache/cord-291523-4dtk1kyh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-291523-4dtk1kyh.txt' === file2bib.sh === id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-290290-wyx9ib7s.txt cache: ./cache/cord-290290-wyx9ib7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290290-wyx9ib7s.txt' === file2bib.sh === id: cord-292152-gmru83ac author: Makrinioti, Heidi title: Intussusception in two children with SARS-CoV-2 infection in children date: 2020-08-08 pages: extension: .txt txt: ./txt/cord-292152-gmru83ac.txt cache: ./cache/cord-292152-gmru83ac.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292152-gmru83ac.txt' === file2bib.sh === id: cord-293056-kz3w0nfh author: Indes, Jeffrey E. title: Early Experience with Arterial Thromboembolic Complications in Patents with COVID-19 date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-293056-kz3w0nfh.txt cache: ./cache/cord-293056-kz3w0nfh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293056-kz3w0nfh.txt' === file2bib.sh === id: cord-289598-t8upoq9a author: Yoon, Jane C title: COVID-19 Prevalence among People Experiencing Homelessness and Homelessness Service Staff during Early Community Transmission in Atlanta, Georgia, April–May 2020 date: 2020-09-08 pages: extension: .txt txt: ./txt/cord-289598-t8upoq9a.txt cache: ./cache/cord-289598-t8upoq9a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289598-t8upoq9a.txt' === file2bib.sh === id: cord-268561-vq1uhj5i author: da Silva, Severino Jefferson Ribeiro title: Clinical and Laboratory Diagnosis of SARS-CoV-2, the Virus Causing COVID-19 date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-268561-vq1uhj5i.txt cache: ./cache/cord-268561-vq1uhj5i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268561-vq1uhj5i.txt' === file2bib.sh === id: cord-292256-jp80u828 author: Moriguchi, Takeshi title: A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 date: 2020-04-03 pages: extension: .txt txt: ./txt/cord-292256-jp80u828.txt cache: ./cache/cord-292256-jp80u828.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292256-jp80u828.txt' === file2bib.sh === id: cord-292742-mio4przi author: McAloose, Denise title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-292742-mio4przi.txt cache: ./cache/cord-292742-mio4przi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292742-mio4przi.txt' === file2bib.sh === id: cord-274141-vujx538o author: Chinsembu, Kazhila C. title: Coronaviruses and Nature’s Pharmacy for the Relief of Coronavirus Disease 2019 date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-274141-vujx538o.txt cache: ./cache/cord-274141-vujx538o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274141-vujx538o.txt' === file2bib.sh === id: cord-290904-ngvhk0qy author: Zheng, Zhiqiang title: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-290904-ngvhk0qy.txt cache: ./cache/cord-290904-ngvhk0qy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290904-ngvhk0qy.txt' === file2bib.sh === id: cord-293890-thfros7x author: Carbo, Ellen C. title: Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-293890-thfros7x.txt cache: ./cache/cord-293890-thfros7x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293890-thfros7x.txt' === file2bib.sh === id: cord-291436-cu5o8ipw author: Martínez-Hernández, Fernando title: Assessing the SARS-CoV-2 threat to wildlife: Potential risk to a broad range of mammals date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-291436-cu5o8ipw.txt cache: ./cache/cord-291436-cu5o8ipw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-291436-cu5o8ipw.txt' === file2bib.sh === id: cord-300041-1d9xu4ts author: Chen, Sharon C-A title: Focus on SARS-CoV-2 and COVID-19 date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-300041-1d9xu4ts.txt cache: ./cache/cord-300041-1d9xu4ts.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300041-1d9xu4ts.txt' === file2bib.sh === id: cord-293691-ewerquin author: Sauerhering, Lucie title: Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-293691-ewerquin.txt cache: ./cache/cord-293691-ewerquin.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293691-ewerquin.txt' === file2bib.sh === id: cord-294069-7zr77r71 author: Hu, Xiaowen title: The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-294069-7zr77r71.txt cache: ./cache/cord-294069-7zr77r71.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294069-7zr77r71.txt' === file2bib.sh === id: cord-298850-tgxfki7n author: Figuero-Pérez, Luis title: Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-298850-tgxfki7n.txt cache: ./cache/cord-298850-tgxfki7n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298850-tgxfki7n.txt' === file2bib.sh === id: cord-291710-ixun0c8g author: Su, Haixia title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-291710-ixun0c8g.txt cache: ./cache/cord-291710-ixun0c8g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-291710-ixun0c8g.txt' === file2bib.sh === id: cord-291397-look6ddt author: Roberto, Palumbo title: Current treatment of COVID-19 in renal patients: hope or hype? date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-291397-look6ddt.txt cache: ./cache/cord-291397-look6ddt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-291397-look6ddt.txt' === file2bib.sh === id: cord-293988-f5gvwjyh author: Musso, Nicolò title: New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-293988-f5gvwjyh.txt cache: ./cache/cord-293988-f5gvwjyh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-293988-f5gvwjyh.txt' === file2bib.sh === id: cord-293578-yu2i0u2h author: Kusadasi, Nuray title: A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-293578-yu2i0u2h.txt cache: ./cache/cord-293578-yu2i0u2h.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293578-yu2i0u2h.txt' === file2bib.sh === id: cord-296237-i9cti2ok author: Díez, José-María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-296237-i9cti2ok.txt cache: ./cache/cord-296237-i9cti2ok.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-296237-i9cti2ok.txt' === file2bib.sh === id: cord-298989-qk0k2lmz author: , Umesh title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-298989-qk0k2lmz.txt cache: ./cache/cord-298989-qk0k2lmz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298989-qk0k2lmz.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-293274-ysr1l557 author: Perisé-Barrios, Ana Judith title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-293274-ysr1l557.txt cache: ./cache/cord-293274-ysr1l557.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293274-ysr1l557.txt' === file2bib.sh === id: cord-296362-9vi8xwu7 author: Wang, Jian-Min title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function date: 2008-09-12 pages: extension: .txt txt: ./txt/cord-296362-9vi8xwu7.txt cache: ./cache/cord-296362-9vi8xwu7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296362-9vi8xwu7.txt' === file2bib.sh === id: cord-296268-kb7fgfaq author: Mendonça, Luiza title: SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-296268-kb7fgfaq.txt cache: ./cache/cord-296268-kb7fgfaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296268-kb7fgfaq.txt' === file2bib.sh === id: cord-298669-g2up0cfi author: Pollock, David D title: Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2 date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-298669-g2up0cfi.txt cache: ./cache/cord-298669-g2up0cfi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298669-g2up0cfi.txt' === file2bib.sh === id: cord-294912-xl0wzi16 author: Alteri, Claudia title: Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date: 2020-09-08 pages: extension: .txt txt: ./txt/cord-294912-xl0wzi16.txt cache: ./cache/cord-294912-xl0wzi16.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294912-xl0wzi16.txt' === file2bib.sh === id: cord-306581-g3d0lqxp author: Khattab, Mohamed H. title: Early detection of SARS-CoV-2 from staging PET-CT date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-306581-g3d0lqxp.txt cache: ./cache/cord-306581-g3d0lqxp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306581-g3d0lqxp.txt' === file2bib.sh === id: cord-301693-3hsu2u1k author: He, Yuwen title: Value of Viral Nucleic Acid in Sputum and Feces and Specific IgM/IgG in Serum for the Diagnosis of Coronavirus Disease 2019 date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-301693-3hsu2u1k.txt cache: ./cache/cord-301693-3hsu2u1k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301693-3hsu2u1k.txt' === file2bib.sh === id: cord-302584-fwdpzv85 author: Zhu, Ying title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates date: 2005-01-01 pages: extension: .txt txt: ./txt/cord-302584-fwdpzv85.txt cache: ./cache/cord-302584-fwdpzv85.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302584-fwdpzv85.txt' === file2bib.sh === id: cord-305931-0pgu2gvh author: Janus, Scott E title: COVID19: a case report of thrombus in transit date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-305931-0pgu2gvh.txt cache: ./cache/cord-305931-0pgu2gvh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-305931-0pgu2gvh.txt' === file2bib.sh === id: cord-305587-xtqvtleb author: Ma, Cuiqing title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-305587-xtqvtleb.txt cache: ./cache/cord-305587-xtqvtleb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305587-xtqvtleb.txt' === file2bib.sh === id: cord-305704-grzrkff9 author: Almutairi, Abdulelah title: Dermatological Manifestations in Patients With SARS-CoV-2: A Systematic Review date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-305704-grzrkff9.txt cache: ./cache/cord-305704-grzrkff9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-305704-grzrkff9.txt' === file2bib.sh === id: cord-296986-8fuj072z author: Kumar, Manish title: A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-296986-8fuj072z.txt cache: ./cache/cord-296986-8fuj072z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296986-8fuj072z.txt' === file2bib.sh === id: cord-297941-7yut9vt4 author: Haq, M. title: Seroprevalence and Risk Factors of SARS CoV-2 in Health Care Workers of Tertiary-Care Hospitals in the Province of Khyber Pakhtunkhwa, Pakistan date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-297941-7yut9vt4.txt cache: ./cache/cord-297941-7yut9vt4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297941-7yut9vt4.txt' === file2bib.sh === id: cord-302608-fw4pmaoc author: Huang, Jiao-Mei title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-302608-fw4pmaoc.txt cache: ./cache/cord-302608-fw4pmaoc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302608-fw4pmaoc.txt' === file2bib.sh === id: cord-303216-1pbuywz6 author: Das, Gaurav title: Neurological Insights of COVID-19 Pandemic date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-303216-1pbuywz6.txt cache: ./cache/cord-303216-1pbuywz6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303216-1pbuywz6.txt' === file2bib.sh === id: cord-296250-7ln7p715 author: Wang, Sheng-Fan title: The pharmacological development of direct acting agents for emerging needed therapy against severe acute respiratory syndrome coronavirus-2 date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-296250-7ln7p715.txt cache: ./cache/cord-296250-7ln7p715.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296250-7ln7p715.txt' === file2bib.sh === id: cord-297786-jz1d1m2e author: Hasan, Md. Mahbub title: Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-297786-jz1d1m2e.txt cache: ./cache/cord-297786-jz1d1m2e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297786-jz1d1m2e.txt' === file2bib.sh === id: cord-304295-3mpymd8a author: Khan, Muhammad Muzamil title: Emergence of novel coronavirus and progress toward treatment and vaccine date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-304295-3mpymd8a.txt cache: ./cache/cord-304295-3mpymd8a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304295-3mpymd8a.txt' === file2bib.sh === id: cord-303297-fiievwy7 author: Oberemok, Volodymyr V. title: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-303297-fiievwy7.txt cache: ./cache/cord-303297-fiievwy7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303297-fiievwy7.txt' === file2bib.sh === id: cord-294831-pem059zk author: Zhang, Ling-Pu title: Focus on a 2019-novel coronavirus (SARS-CoV-2) date: 2020-06-11 pages: extension: .txt txt: ./txt/cord-294831-pem059zk.txt cache: ./cache/cord-294831-pem059zk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294831-pem059zk.txt' === file2bib.sh === id: cord-308342-ycdok8fc author: Shutler, J. title: Risk of SARS-CoV-2 infection from contaminated water systems date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-308342-ycdok8fc.txt cache: ./cache/cord-308342-ycdok8fc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308342-ycdok8fc.txt' === file2bib.sh === id: cord-308110-cco3aq4n author: Okamoto, Mika title: The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date: 2020-07-30 pages: extension: .txt txt: ./txt/cord-308110-cco3aq4n.txt cache: ./cache/cord-308110-cco3aq4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-308110-cco3aq4n.txt' === file2bib.sh === id: cord-304263-5kddk5fa author: C., Selvaa Kumar title: Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2 date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-304263-5kddk5fa.txt cache: ./cache/cord-304263-5kddk5fa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304263-5kddk5fa.txt' === file2bib.sh === id: cord-304792-8sdxqmkb author: Khan, Md. Abdullah-Al-Kamran title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-304792-8sdxqmkb.txt cache: ./cache/cord-304792-8sdxqmkb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304792-8sdxqmkb.txt' === file2bib.sh === id: cord-296602-19noki6p author: Law, Helen KW title: Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells date: 2009-06-08 pages: extension: .txt txt: ./txt/cord-296602-19noki6p.txt cache: ./cache/cord-296602-19noki6p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296602-19noki6p.txt' === file2bib.sh === id: cord-300968-dtaasxk1 author: Kliger, Yossef title: From genome to antivirals: SARS as a test tube date: 2005-03-01 pages: extension: .txt txt: ./txt/cord-300968-dtaasxk1.txt cache: ./cache/cord-300968-dtaasxk1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300968-dtaasxk1.txt' === file2bib.sh === id: cord-297842-hkr1wm3k author: Tilley, Kimberly title: A Cross-Sectional Study Examining the Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in a University Student Population date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-297842-hkr1wm3k.txt cache: ./cache/cord-297842-hkr1wm3k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297842-hkr1wm3k.txt' === file2bib.sh === id: cord-297132-lhfa9fl5 author: Aghagoli, Ghazal title: Neurological Involvement in COVID-19 and Potential Mechanisms: A Review date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-297132-lhfa9fl5.txt cache: ./cache/cord-297132-lhfa9fl5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297132-lhfa9fl5.txt' === file2bib.sh === id: cord-296426-upwsdgso author: Virmani, Sarthak title: Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-296426-upwsdgso.txt cache: ./cache/cord-296426-upwsdgso.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296426-upwsdgso.txt' === file2bib.sh === id: cord-268540-wrjzr3ws author: Park, You Jeong title: Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-268540-wrjzr3ws.txt cache: ./cache/cord-268540-wrjzr3ws.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268540-wrjzr3ws.txt' === file2bib.sh === id: cord-294212-nlekz39f author: Wang, Dongliang title: Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-294212-nlekz39f.txt cache: ./cache/cord-294212-nlekz39f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294212-nlekz39f.txt' === file2bib.sh === id: cord-301974-4wn40ivq author: Berry, Jody D title: Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus date: 2004-09-01 pages: extension: .txt txt: ./txt/cord-301974-4wn40ivq.txt cache: ./cache/cord-301974-4wn40ivq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301974-4wn40ivq.txt' === file2bib.sh === id: cord-309289-vm0k7hfx author: Rothan, Hussin A. title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-309289-vm0k7hfx.txt cache: ./cache/cord-309289-vm0k7hfx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309289-vm0k7hfx.txt' === file2bib.sh === id: cord-294136-e69ao8j0 author: Han, Dongsheng title: COVID-19: Insight into the asymptomatic SARS-COV-2 infection and transmission date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-294136-e69ao8j0.txt cache: ./cache/cord-294136-e69ao8j0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294136-e69ao8j0.txt' === file2bib.sh === id: cord-307701-fujejfwb author: Gaurav, Shubham title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 pages: extension: .txt txt: ./txt/cord-307701-fujejfwb.txt cache: ./cache/cord-307701-fujejfwb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307701-fujejfwb.txt' === file2bib.sh === id: cord-306373-61snvddh author: Xu, Xiao-Wei title: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series date: 2020-02-19 pages: extension: .txt txt: ./txt/cord-306373-61snvddh.txt cache: ./cache/cord-306373-61snvddh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306373-61snvddh.txt' === file2bib.sh === id: cord-307489-2liu4anc author: Elavia, Nasha title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia date: 2020-05-23 pages: extension: .txt txt: ./txt/cord-307489-2liu4anc.txt cache: ./cache/cord-307489-2liu4anc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307489-2liu4anc.txt' === file2bib.sh === id: cord-298067-awo3smgp author: Li, Huanjie title: Transmission Routes Analysis of SARS-CoV-2: A Systematic Review and Case Report date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-298067-awo3smgp.txt cache: ./cache/cord-298067-awo3smgp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-298067-awo3smgp.txt' === file2bib.sh === id: cord-302707-cap2rgf7 author: Ng, Dianna L. title: SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-302707-cap2rgf7.txt cache: ./cache/cord-302707-cap2rgf7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-302707-cap2rgf7.txt' === file2bib.sh === id: cord-259603-bh198xgl author: Snijder, E.J. title: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date: 2016-09-14 pages: extension: .txt txt: ./txt/cord-259603-bh198xgl.txt cache: ./cache/cord-259603-bh198xgl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259603-bh198xgl.txt' === file2bib.sh === id: cord-297332-rzf0cw1x author: Wang, Qidi title: Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates date: 2016-04-11 pages: extension: .txt txt: ./txt/cord-297332-rzf0cw1x.txt cache: ./cache/cord-297332-rzf0cw1x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297332-rzf0cw1x.txt' === file2bib.sh === id: cord-301730-flv5lnv8 author: Pandey, Anamika title: Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-301730-flv5lnv8.txt cache: ./cache/cord-301730-flv5lnv8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301730-flv5lnv8.txt' === file2bib.sh === id: cord-304073-f3iwclkm author: Mullick, Jhinuk Basu title: Animal Models to Study Emerging Technologies Against SARS-CoV-2 date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-304073-f3iwclkm.txt cache: ./cache/cord-304073-f3iwclkm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304073-f3iwclkm.txt' === file2bib.sh === id: cord-296219-zzg9hds0 author: Battaglini, Denise title: Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-296219-zzg9hds0.txt cache: ./cache/cord-296219-zzg9hds0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296219-zzg9hds0.txt' === file2bib.sh === id: cord-293852-r72c6584 author: Greco, S. title: Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era date: 2020-10-31 pages: extension: .txt txt: ./txt/cord-293852-r72c6584.txt cache: ./cache/cord-293852-r72c6584.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293852-r72c6584.txt' === file2bib.sh === id: cord-297599-y4lu8m4k author: Luo, Hua title: Anti-COVID-19 drug screening: Frontier concepts and core technologies date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-297599-y4lu8m4k.txt cache: ./cache/cord-297599-y4lu8m4k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297599-y4lu8m4k.txt' === file2bib.sh === id: cord-304617-5ozf18lg author: Al-Khafaji, Khattab title: Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2 date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-304617-5ozf18lg.txt cache: ./cache/cord-304617-5ozf18lg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-304617-5ozf18lg.txt' === file2bib.sh === id: cord-306177-5wefp31y author: Iheagwam, Franklyn Nonso title: Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants date: 2020-09-12 pages: extension: .txt txt: ./txt/cord-306177-5wefp31y.txt cache: ./cache/cord-306177-5wefp31y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306177-5wefp31y.txt' === file2bib.sh === id: cord-305856-xt3zxajf author: Shanmugam, Chandrakumar title: COVID-2019 – A comprehensive pathology insight date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-305856-xt3zxajf.txt cache: ./cache/cord-305856-xt3zxajf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305856-xt3zxajf.txt' === file2bib.sh === id: cord-303741-1ou0cy5k author: Stafstrom, Carl E. title: COVID-19: Neurological Considerations in Neonates and Children date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-303741-1ou0cy5k.txt cache: ./cache/cord-303741-1ou0cy5k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303741-1ou0cy5k.txt' === file2bib.sh === id: cord-310807-p5cb6idp author: Kanwar, Anubhav title: Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio date: 2017-03-25 pages: extension: .txt txt: ./txt/cord-310807-p5cb6idp.txt cache: ./cache/cord-310807-p5cb6idp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310807-p5cb6idp.txt' === file2bib.sh === id: cord-309418-dx6e0lri author: Segalés, Joaquim title: Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-309418-dx6e0lri.txt cache: ./cache/cord-309418-dx6e0lri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309418-dx6e0lri.txt' === file2bib.sh === id: cord-308583-vtmwv8zl author: Du, Qishi title: Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase date: 2005-02-15 pages: extension: .txt txt: ./txt/cord-308583-vtmwv8zl.txt cache: ./cache/cord-308583-vtmwv8zl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308583-vtmwv8zl.txt' === file2bib.sh === id: cord-309074-pys4aa60 author: Huang, Victoria W. title: Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-309074-pys4aa60.txt cache: ./cache/cord-309074-pys4aa60.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309074-pys4aa60.txt' === file2bib.sh === id: cord-304418-k9owyolj author: Le Maréchal, M. title: COVID-19 in clinical practice: a narrative synthesis date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-304418-k9owyolj.txt cache: ./cache/cord-304418-k9owyolj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-304418-k9owyolj.txt' === file2bib.sh === id: cord-308252-qwoo7b1l author: Cardinale, Vincenzo title: Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-308252-qwoo7b1l.txt cache: ./cache/cord-308252-qwoo7b1l.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308252-qwoo7b1l.txt' === file2bib.sh === id: cord-304306-rxjahqwh author: Vlachakis, Dimitrios title: Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-304306-rxjahqwh.txt cache: ./cache/cord-304306-rxjahqwh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304306-rxjahqwh.txt' === file2bib.sh === id: cord-310507-5h6egve4 author: van Doorn, Amarylle S. title: Systematic review with meta‐analysis: SARS‐CoV‐2 stool testing and the potential for faecal‐oral transmission date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-310507-5h6egve4.txt cache: ./cache/cord-310507-5h6egve4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310507-5h6egve4.txt' === file2bib.sh === id: cord-294527-fct2y5vn author: Guadarrama-Ortiz, Parménides title: Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-294527-fct2y5vn.txt cache: ./cache/cord-294527-fct2y5vn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294527-fct2y5vn.txt' === file2bib.sh === id: cord-309474-9h9w46eq author: Schiaffini, Riccardo title: School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-309474-9h9w46eq.txt cache: ./cache/cord-309474-9h9w46eq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309474-9h9w46eq.txt' === file2bib.sh === id: cord-310221-car394ou author: Chandrashekar, Abishek title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-310221-car394ou.txt cache: ./cache/cord-310221-car394ou.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310221-car394ou.txt' === file2bib.sh === id: cord-294363-bv6xa8v8 author: Zhou, Hong title: Potential Therapeutic Targets and Promising Drugs for Combating SARS‐CoV‐2 date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-294363-bv6xa8v8.txt cache: ./cache/cord-294363-bv6xa8v8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294363-bv6xa8v8.txt' === file2bib.sh === id: cord-311762-f6muhf3d author: Chen, Yu Wai title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates date: 2020-02-21 pages: extension: .txt txt: ./txt/cord-311762-f6muhf3d.txt cache: ./cache/cord-311762-f6muhf3d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-311762-f6muhf3d.txt' === file2bib.sh === id: cord-303517-8971aq02 author: Cajamarca-Baron, Jairo title: SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-303517-8971aq02.txt cache: ./cache/cord-303517-8971aq02.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303517-8971aq02.txt' === file2bib.sh === id: cord-304479-uxp1kg86 author: Goodarzi, Pedram title: Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments date: 2020-08-08 pages: extension: .txt txt: ./txt/cord-304479-uxp1kg86.txt cache: ./cache/cord-304479-uxp1kg86.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304479-uxp1kg86.txt' === file2bib.sh === id: cord-310239-mmvuij3k author: Arentz, Susan title: Clinical significance summary: Preliminary results of a rapid review of zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections date: 2020-08-01 pages: extension: .txt txt: ./txt/cord-310239-mmvuij3k.txt cache: ./cache/cord-310239-mmvuij3k.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310239-mmvuij3k.txt' === file2bib.sh === id: cord-289535-srrfr1es author: Tregoning, J. S. title: Vaccines for COVID‐19 date: 2020-10-18 pages: extension: .txt txt: ./txt/cord-289535-srrfr1es.txt cache: ./cache/cord-289535-srrfr1es.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289535-srrfr1es.txt' === file2bib.sh === id: cord-313505-2lr4xara author: Resende, Paola Cristina title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-313505-2lr4xara.txt cache: ./cache/cord-313505-2lr4xara.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313505-2lr4xara.txt' === file2bib.sh === id: cord-313344-rqvi2ksc author: Farcas, Gabriella A. title: Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus date: 2005-01-15 pages: extension: .txt txt: ./txt/cord-313344-rqvi2ksc.txt cache: ./cache/cord-313344-rqvi2ksc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313344-rqvi2ksc.txt' === file2bib.sh === id: cord-311214-eqwxkwqa author: Kumar, Roshan title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-311214-eqwxkwqa.txt cache: ./cache/cord-311214-eqwxkwqa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311214-eqwxkwqa.txt' === file2bib.sh === id: cord-309633-1cd74xdl author: Rogers, Julia H. title: Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-309633-1cd74xdl.txt cache: ./cache/cord-309633-1cd74xdl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309633-1cd74xdl.txt' === file2bib.sh === id: cord-299093-zp07aqpm author: Harrison, Andrew G. title: Mechanisms of SARS-CoV-2 transmission and pathogenesis date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-299093-zp07aqpm.txt cache: ./cache/cord-299093-zp07aqpm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299093-zp07aqpm.txt' === file2bib.sh === id: cord-312160-2820aftb author: Ibrahim, Mahmoud A.A. title: In silico Drug Discovery of Major Metabolites from Spices as SARS-CoV-2 Main Protease Inhibitors date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-312160-2820aftb.txt cache: ./cache/cord-312160-2820aftb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312160-2820aftb.txt' === file2bib.sh === id: cord-312670-hi3fjne4 author: Corman, V. M. title: Coronaviren als Ursache respiratorischer Infektionen date: 2019-08-27 pages: extension: .txt txt: ./txt/cord-312670-hi3fjne4.txt cache: ./cache/cord-312670-hi3fjne4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312670-hi3fjne4.txt' === file2bib.sh === id: cord-309147-c3ikb81g author: Nadeem, Muhammad Shahid title: Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-309147-c3ikb81g.txt cache: ./cache/cord-309147-c3ikb81g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309147-c3ikb81g.txt' === file2bib.sh === id: cord-314793-kb319t4c author: Borroni, Barbara title: Diaphragmatic myoclonus due to SARS-CoV-2 infection date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-314793-kb319t4c.txt cache: ./cache/cord-314793-kb319t4c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314793-kb319t4c.txt' === file2bib.sh === id: cord-300716-urmogf97 author: Briguglio, Matteo title: Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-300716-urmogf97.txt cache: ./cache/cord-300716-urmogf97.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300716-urmogf97.txt' === file2bib.sh === id: cord-308945-i2agpvhk author: Phipps, William S title: SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-308945-i2agpvhk.txt cache: ./cache/cord-308945-i2agpvhk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308945-i2agpvhk.txt' === file2bib.sh === id: cord-310624-3kojrkz7 author: Flores-Alanis, Alejandro title: The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789 date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-310624-3kojrkz7.txt cache: ./cache/cord-310624-3kojrkz7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310624-3kojrkz7.txt' === file2bib.sh === id: cord-310017-c8rd714a author: Popa, Alexandra title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-310017-c8rd714a.txt cache: ./cache/cord-310017-c8rd714a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310017-c8rd714a.txt' === file2bib.sh === id: cord-312652-zhccmfgw author: Hu, Xiumei title: Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-312652-zhccmfgw.txt cache: ./cache/cord-312652-zhccmfgw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312652-zhccmfgw.txt' === file2bib.sh === id: cord-309876-l0xginsa author: Vena, Antonio title: Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-309876-l0xginsa.txt cache: ./cache/cord-309876-l0xginsa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309876-l0xginsa.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-286683-mettlmhz author: Ortiz-Prado, Esteban title: Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-286683-mettlmhz.txt cache: ./cache/cord-286683-mettlmhz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-286683-mettlmhz.txt' === file2bib.sh === id: cord-316702-dj2fo8sn author: Vignesh, Ramachandran title: Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-316702-dj2fo8sn.txt cache: ./cache/cord-316702-dj2fo8sn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-316702-dj2fo8sn.txt' === file2bib.sh === id: cord-302382-eifh95zm author: Owji, Hajar title: Immunotherapeutic approaches to curtail COVID-19 date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-302382-eifh95zm.txt cache: ./cache/cord-302382-eifh95zm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302382-eifh95zm.txt' === file2bib.sh === id: cord-319184-voc0eqb9 author: Abduljalil, Jameel M. title: Laboratory diagnosis of SARS-CoV-2: available approaches and limitations date: 2020-06-14 pages: extension: .txt txt: ./txt/cord-319184-voc0eqb9.txt cache: ./cache/cord-319184-voc0eqb9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319184-voc0eqb9.txt' === file2bib.sh === id: cord-313517-5ipj2z86 author: Fung, Joshua title: Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans date: 2019-09-14 pages: extension: .txt txt: ./txt/cord-313517-5ipj2z86.txt cache: ./cache/cord-313517-5ipj2z86.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313517-5ipj2z86.txt' === file2bib.sh === id: cord-314445-4cb4a9r5 author: McNamara, Ryan P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-314445-4cb4a9r5.txt cache: ./cache/cord-314445-4cb4a9r5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314445-4cb4a9r5.txt' === file2bib.sh === id: cord-311114-ggcpsjk8 author: Radhakrishnan, Chandni title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-311114-ggcpsjk8.txt cache: ./cache/cord-311114-ggcpsjk8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311114-ggcpsjk8.txt' === file2bib.sh === id: cord-318204-t024w7h6 author: Fang, Ferric C title: The Laboratory Diagnosis of COVID-19-- Frequently-Asked Questions date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-318204-t024w7h6.txt cache: ./cache/cord-318204-t024w7h6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318204-t024w7h6.txt' === file2bib.sh === id: cord-309138-44qpk2vf author: Khanna, Kanika title: Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle date: 2020-10-03 pages: extension: .txt txt: ./txt/cord-309138-44qpk2vf.txt cache: ./cache/cord-309138-44qpk2vf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309138-44qpk2vf.txt' === file2bib.sh === id: cord-308857-otsrexqu author: Goel, Saurav title: Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-308857-otsrexqu.txt cache: ./cache/cord-308857-otsrexqu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308857-otsrexqu.txt' === file2bib.sh === id: cord-312664-tgpaidhp author: Liang, Julia title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-312664-tgpaidhp.txt cache: ./cache/cord-312664-tgpaidhp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312664-tgpaidhp.txt' === file2bib.sh === id: cord-315064-2mgv9j6n author: Escher, Felicitas title: Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-315064-2mgv9j6n.txt cache: ./cache/cord-315064-2mgv9j6n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315064-2mgv9j6n.txt' === file2bib.sh === id: cord-314669-lvibjx97 author: Shang, Guifang title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 date: 2007-11-26 pages: extension: .txt txt: ./txt/cord-314669-lvibjx97.txt cache: ./cache/cord-314669-lvibjx97.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314669-lvibjx97.txt' === file2bib.sh === id: cord-318164-6rqi17oz author: Paoli, D. title: Sperm cryopreservation during the SARS-CoV-2 pandemic date: 2020-10-10 pages: extension: .txt txt: ./txt/cord-318164-6rqi17oz.txt cache: ./cache/cord-318164-6rqi17oz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-318164-6rqi17oz.txt' === file2bib.sh === id: cord-315288-fcx4q6mp author: Hussain, Mohammed Hassan title: Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-315288-fcx4q6mp.txt cache: ./cache/cord-315288-fcx4q6mp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315288-fcx4q6mp.txt' === file2bib.sh === id: cord-317355-z5tk3v3b author: Dunker, Susanne title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-317355-z5tk3v3b.txt cache: ./cache/cord-317355-z5tk3v3b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-317355-z5tk3v3b.txt' === file2bib.sh === id: cord-314051-dr27bsvt author: Lother, Sylvain A. title: Preoperative SARS-CoV-2 screening: Can it really rule out COVID-19? date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-314051-dr27bsvt.txt cache: ./cache/cord-314051-dr27bsvt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314051-dr27bsvt.txt' === file2bib.sh === id: cord-324480-7u5lh4jx author: Sharma, A. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-324480-7u5lh4jx.txt cache: ./cache/cord-324480-7u5lh4jx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324480-7u5lh4jx.txt' === file2bib.sh === id: cord-307860-iqk1yiw4 author: Ionescu, Mihaela Ileana title: An Overview of the Crystallized Structures of the SARS-CoV-2 date: 2020-10-24 pages: extension: .txt txt: ./txt/cord-307860-iqk1yiw4.txt cache: ./cache/cord-307860-iqk1yiw4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307860-iqk1yiw4.txt' === file2bib.sh === id: cord-287758-da11ypiy author: Mônica Vitalino de Almeida, Sinara title: COVID-19 therapy: what weapons do we bring into battle? date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-287758-da11ypiy.txt cache: ./cache/cord-287758-da11ypiy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-287758-da11ypiy.txt' === file2bib.sh === id: cord-274802-7ioiwsd8 author: Varghese, Praveen Mathews title: Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-274802-7ioiwsd8.txt cache: ./cache/cord-274802-7ioiwsd8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274802-7ioiwsd8.txt' === file2bib.sh === id: cord-318934-dxipu00r author: Matsuyama, Shutoku title: Enhancement of SARS-CoV Infection by Proteases date: 2006 pages: extension: .txt txt: ./txt/cord-318934-dxipu00r.txt cache: ./cache/cord-318934-dxipu00r.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318934-dxipu00r.txt' === file2bib.sh === id: cord-294108-uvnh0s9r author: Dube, Taru title: Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector date: 2020-10-25 pages: extension: .txt txt: ./txt/cord-294108-uvnh0s9r.txt cache: ./cache/cord-294108-uvnh0s9r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294108-uvnh0s9r.txt' === file2bib.sh === id: cord-312305-ll29frwc author: Sun, Shihui title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 pages: extension: .txt txt: ./txt/cord-312305-ll29frwc.txt cache: ./cache/cord-312305-ll29frwc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312305-ll29frwc.txt' === file2bib.sh === id: cord-319194-ukuia48s author: Liò, Pietro title: Phylogenomics and bioinformatics of SARS-CoV date: 2004-02-04 pages: extension: .txt txt: ./txt/cord-319194-ukuia48s.txt cache: ./cache/cord-319194-ukuia48s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319194-ukuia48s.txt' === file2bib.sh === id: cord-291916-5yqc3zcx author: Hozhabri, Hossein title: The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-291916-5yqc3zcx.txt cache: ./cache/cord-291916-5yqc3zcx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291916-5yqc3zcx.txt' === file2bib.sh === id: cord-324557-4u8dja0n author: Leblanc, Jean‐François title: Risk of Transmission of Severe Acute Respiratory Syndrome Coronavirus‐2 by Transfusion: A Literature Review date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-324557-4u8dja0n.txt cache: ./cache/cord-324557-4u8dja0n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324557-4u8dja0n.txt' === file2bib.sh === id: cord-317786-iv1br2oj author: Waterfield, T. title: Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study. date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-317786-iv1br2oj.txt cache: ./cache/cord-317786-iv1br2oj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317786-iv1br2oj.txt' === file2bib.sh === id: cord-322051-89wgv100 author: Tanasa, Ingrid Andrada title: Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known? date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-322051-89wgv100.txt cache: ./cache/cord-322051-89wgv100.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322051-89wgv100.txt' === file2bib.sh === id: cord-315085-rucfowvv author: Sekulic, Miroslav title: Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-315085-rucfowvv.txt cache: ./cache/cord-315085-rucfowvv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315085-rucfowvv.txt' === file2bib.sh === id: cord-314135-udce22id author: Geisslinger, Franz title: Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa? date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-314135-udce22id.txt cache: ./cache/cord-314135-udce22id.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314135-udce22id.txt' === file2bib.sh === id: cord-318316-9unfl966 author: Ortega, Joseph T. title: Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-318316-9unfl966.txt cache: ./cache/cord-318316-9unfl966.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318316-9unfl966.txt' === file2bib.sh === id: cord-322837-tqgwgvo0 author: Gable, Lance title: Legal and Ethical Implications of Wastewater SARS-CoV-2 Monitoring for COVID-19 Surveillance date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-322837-tqgwgvo0.txt cache: ./cache/cord-322837-tqgwgvo0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-322837-tqgwgvo0.txt' === file2bib.sh === id: cord-311848-8n9ee57a author: Giesen, Nicola title: Evidence-based Management of COVID-19 in Cancer Patients – Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-311848-8n9ee57a.txt cache: ./cache/cord-311848-8n9ee57a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311848-8n9ee57a.txt' === file2bib.sh === id: cord-322811-6lebh7ca author: Baig, Mirza S. title: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-322811-6lebh7ca.txt cache: ./cache/cord-322811-6lebh7ca.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322811-6lebh7ca.txt' === file2bib.sh === id: cord-321624-z2mntwef author: Kowitdamrong, Ekasit title: Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-321624-z2mntwef.txt cache: ./cache/cord-321624-z2mntwef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321624-z2mntwef.txt' === file2bib.sh === id: cord-321358-plxz5mkg author: Zheng, Jun title: SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat date: 2020-03-15 pages: extension: .txt txt: ./txt/cord-321358-plxz5mkg.txt cache: ./cache/cord-321358-plxz5mkg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-321358-plxz5mkg.txt' === file2bib.sh === id: cord-311847-2czqs84q author: Pennisi, Manuela title: SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-311847-2czqs84q.txt cache: ./cache/cord-311847-2czqs84q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311847-2czqs84q.txt' === file2bib.sh === id: cord-320619-r466dc5t author: Chand Dakal, Tikam title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-320619-r466dc5t.txt cache: ./cache/cord-320619-r466dc5t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320619-r466dc5t.txt' === file2bib.sh === id: cord-319241-div9rzax author: Singh, Bhuchitra title: Severe Acute Respiratory Syndrome‐Corona Virus‐2 (SARS‐CoV‐2) and its Effect on Gametogenesis and Early Pregnancy date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-319241-div9rzax.txt cache: ./cache/cord-319241-div9rzax.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-319241-div9rzax.txt' === file2bib.sh === id: cord-323061-0i5w7vm9 author: Kharel Sitaula, Ranju title: Unfolding COVID-19: Lessons-in-Learning in Ophthalmology date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-323061-0i5w7vm9.txt cache: ./cache/cord-323061-0i5w7vm9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323061-0i5w7vm9.txt' === file2bib.sh === id: cord-321855-7b1c2xdh author: Alshami, Alanoud title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-321855-7b1c2xdh.txt cache: ./cache/cord-321855-7b1c2xdh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321855-7b1c2xdh.txt' === file2bib.sh === id: cord-300399-21xozruq author: Jayamohan, Harikrishnan title: SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations date: 2020-10-18 pages: extension: .txt txt: ./txt/cord-300399-21xozruq.txt cache: ./cache/cord-300399-21xozruq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300399-21xozruq.txt' === file2bib.sh === id: cord-315685-ute3dxwu author: Ehaideb, Salleh N. title: Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-315685-ute3dxwu.txt cache: ./cache/cord-315685-ute3dxwu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315685-ute3dxwu.txt' === file2bib.sh === id: cord-314171-431buxxr author: Dariya, Begum title: Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients date: 2020-05-06 pages: extension: .txt txt: ./txt/cord-314171-431buxxr.txt cache: ./cache/cord-314171-431buxxr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314171-431buxxr.txt' === file2bib.sh === id: cord-322908-e3gok0ot author: Huang, Fangfang title: A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-322908-e3gok0ot.txt cache: ./cache/cord-322908-e3gok0ot.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322908-e3gok0ot.txt' === file2bib.sh === id: cord-311125-v9ddes3c author: Cooper, Keiland W. title: COVID-19 and the chemical senses: supporting players take center stage date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-311125-v9ddes3c.txt cache: ./cache/cord-311125-v9ddes3c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311125-v9ddes3c.txt' === file2bib.sh === id: cord-323905-ayufx3wv author: Kort, N. P. title: Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-323905-ayufx3wv.txt cache: ./cache/cord-323905-ayufx3wv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323905-ayufx3wv.txt' === file2bib.sh === id: cord-325959-uqg2xkie author: Bundschuh, Christian title: Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-325959-uqg2xkie.txt cache: ./cache/cord-325959-uqg2xkie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325959-uqg2xkie.txt' === file2bib.sh === id: cord-324102-75v4ebag author: Garcia Rodriguez, Alejandro title: SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-324102-75v4ebag.txt cache: ./cache/cord-324102-75v4ebag.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324102-75v4ebag.txt' === file2bib.sh === id: cord-328361-hyrke6j2 author: Ithete, Ndapewa Laudika title: Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa date: 2013-10-17 pages: extension: .txt txt: ./txt/cord-328361-hyrke6j2.txt cache: ./cache/cord-328361-hyrke6j2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-328361-hyrke6j2.txt' === file2bib.sh === id: cord-324919-ciamusjs author: Scialo, Filippo title: ACE2: The Major Cell Entry Receptor for SARS-CoV-2 date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-324919-ciamusjs.txt cache: ./cache/cord-324919-ciamusjs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324919-ciamusjs.txt' === file2bib.sh === id: cord-321851-ku4z34lu author: Alosaimi, Bandar title: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract date: 2020-02-29 pages: extension: .txt txt: ./txt/cord-321851-ku4z34lu.txt cache: ./cache/cord-321851-ku4z34lu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321851-ku4z34lu.txt' === file2bib.sh === id: cord-325614-e9hnhzfg author: Todorov, German title: A Possible Path towards Rapid Development of Live-Attenuated SARS-CoV-2 Vaccines: Plunging into the Natural Pool date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-325614-e9hnhzfg.txt cache: ./cache/cord-325614-e9hnhzfg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325614-e9hnhzfg.txt' === file2bib.sh === id: cord-327654-9g8zcxaa author: Chi, Xiaojing title: Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-327654-9g8zcxaa.txt cache: ./cache/cord-327654-9g8zcxaa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327654-9g8zcxaa.txt' === file2bib.sh === id: cord-322957-clf8f90t author: Crespo, Javier title: Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-322957-clf8f90t.txt cache: ./cache/cord-322957-clf8f90t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322957-clf8f90t.txt' === file2bib.sh === id: cord-327690-di7hfghi author: Yang, Xiaobo title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study date: 2020-02-24 pages: extension: .txt txt: ./txt/cord-327690-di7hfghi.txt cache: ./cache/cord-327690-di7hfghi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327690-di7hfghi.txt' === file2bib.sh === id: cord-322129-uyswj4ow author: Melin, Amanda D. title: Comparative ACE2 variation and primate COVID-19 risk date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-322129-uyswj4ow.txt cache: ./cache/cord-322129-uyswj4ow.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322129-uyswj4ow.txt' === file2bib.sh === id: cord-325324-kh2aal5n author: Teng, Shaolei title: ACE2 Enhance Viral Infection or Viral Infection Aggravate the Underlying Diseases date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-325324-kh2aal5n.txt cache: ./cache/cord-325324-kh2aal5n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325324-kh2aal5n.txt' === file2bib.sh === id: cord-323093-u3ozc9ry author: Rathnayake, Athri D. title: 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-323093-u3ozc9ry.txt cache: ./cache/cord-323093-u3ozc9ry.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323093-u3ozc9ry.txt' === file2bib.sh === id: cord-320935-3n157yl4 author: Kumar, Manish title: Making Waves Perspectives of Modelling and Monitoring of SARS-CoV-2 in Aquatic Environment for COVID-19 Pandemic date: 2020-09-12 pages: extension: .txt txt: ./txt/cord-320935-3n157yl4.txt cache: ./cache/cord-320935-3n157yl4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320935-3n157yl4.txt' === file2bib.sh === id: cord-314451-mqnqjn0c author: Roberts, Anjeanette title: A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date: 2007-01-12 pages: extension: .txt txt: ./txt/cord-314451-mqnqjn0c.txt cache: ./cache/cord-314451-mqnqjn0c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314451-mqnqjn0c.txt' === file2bib.sh === id: cord-328996-3sf2i45r author: Barthélémy, Romain title: Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome date: 2020-06-06 pages: extension: .txt txt: ./txt/cord-328996-3sf2i45r.txt cache: ./cache/cord-328996-3sf2i45r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328996-3sf2i45r.txt' === file2bib.sh === id: cord-323666-t7cshj05 author: Cegolon, L. title: Nasal Disinfection for the Prevention and Control of COVID-19: A Scoping Review on Potential Chemo-preventive Agents. date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-323666-t7cshj05.txt cache: ./cache/cord-323666-t7cshj05.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323666-t7cshj05.txt' === file2bib.sh === id: cord-321901-zpi7uis1 author: Roberts, Anjeanette title: Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK date: 2006-11-30 pages: extension: .txt txt: ./txt/cord-321901-zpi7uis1.txt cache: ./cache/cord-321901-zpi7uis1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321901-zpi7uis1.txt' === file2bib.sh === id: cord-325014-n7mnhk2v author: Gujski, Mariusz title: Prevalence of Current and Past SARS-CoV-2 Infections among Police Employees in Poland, June–July 2020 date: 2020-10-11 pages: extension: .txt txt: ./txt/cord-325014-n7mnhk2v.txt cache: ./cache/cord-325014-n7mnhk2v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325014-n7mnhk2v.txt' === file2bib.sh === id: cord-326013-5i35zdmv author: Carpinteiro, Alexander title: Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-326013-5i35zdmv.txt cache: ./cache/cord-326013-5i35zdmv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326013-5i35zdmv.txt' === file2bib.sh === id: cord-326706-75mjs6vm author: Waterfield, Thomas title: Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-326706-75mjs6vm.txt cache: ./cache/cord-326706-75mjs6vm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326706-75mjs6vm.txt' === file2bib.sh === id: cord-331856-j0gedx43 author: Basile, K. title: Accuracy amidst ambiguity: false positive SARS-CoV-2 nucleic acid tests when COVID-19 prevalence is low date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-331856-j0gedx43.txt cache: ./cache/cord-331856-j0gedx43.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331856-j0gedx43.txt' === file2bib.sh === id: cord-324856-hf969tav author: Abir, Tanvir title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-324856-hf969tav.txt cache: ./cache/cord-324856-hf969tav.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-324856-hf969tav.txt' === file2bib.sh === id: cord-331429-mh2hd5fe author: Srikantiah, Padmini title: SARS Clinical Features, United States, 2003 date: 2005-01-17 pages: extension: .txt txt: ./txt/cord-331429-mh2hd5fe.txt cache: ./cache/cord-331429-mh2hd5fe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331429-mh2hd5fe.txt' === file2bib.sh === id: cord-319877-izn315hb author: de Wit, Emmie title: SARS and MERS: recent insights into emerging coronaviruses date: 2016-06-27 pages: extension: .txt txt: ./txt/cord-319877-izn315hb.txt cache: ./cache/cord-319877-izn315hb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-319877-izn315hb.txt' === file2bib.sh === id: cord-328175-4i3cz20j author: van Doremalen, Neeltje title: Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets date: 2017-07-31 pages: extension: .txt txt: ./txt/cord-328175-4i3cz20j.txt cache: ./cache/cord-328175-4i3cz20j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328175-4i3cz20j.txt' === file2bib.sh === id: cord-312486-rumqopg0 author: Jacob, Chaim Oscar title: On the genetics and immunopathogenesis of COVID-19 date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-312486-rumqopg0.txt cache: ./cache/cord-312486-rumqopg0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312486-rumqopg0.txt' === file2bib.sh === id: cord-332080-923jpec0 author: Lai, Chih-Cheng title: In vitro diagnostics of coronavirus disease 2019: technologies and application date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-332080-923jpec0.txt cache: ./cache/cord-332080-923jpec0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332080-923jpec0.txt' === file2bib.sh === id: cord-325234-skshcrh1 author: Jin, Tingxu title: SARS-CoV-2 presented in the air of an intensive care unit (ICU) date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-325234-skshcrh1.txt cache: ./cache/cord-325234-skshcrh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325234-skshcrh1.txt' === file2bib.sh === id: cord-332595-874tpi09 author: Salehi, Najmeh title: Profiling of Initial Available SARS-CoV-2 Sequences from Iranian Related COVID-19 Patients date: 2020-09-08 pages: extension: .txt txt: ./txt/cord-332595-874tpi09.txt cache: ./cache/cord-332595-874tpi09.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332595-874tpi09.txt' === file2bib.sh === id: cord-324978-9qfhsj3n author: Alagaili, Abdulaziz N. title: Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date: 2014-02-25 pages: extension: .txt txt: ./txt/cord-324978-9qfhsj3n.txt cache: ./cache/cord-324978-9qfhsj3n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324978-9qfhsj3n.txt' === file2bib.sh === id: cord-331039-qgom2e3n author: Kavitha, Kuppuswamy title: 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-331039-qgom2e3n.txt cache: ./cache/cord-331039-qgom2e3n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331039-qgom2e3n.txt' === file2bib.sh === id: cord-329011-spiuqngp author: Huang, Yuan title: Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 date: 2020-08-03 pages: extension: .txt txt: ./txt/cord-329011-spiuqngp.txt cache: ./cache/cord-329011-spiuqngp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329011-spiuqngp.txt' === file2bib.sh === id: cord-331193-33cyvidx author: Mawhinney, Jamie A title: Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode date: 2020-06-14 pages: extension: .txt txt: ./txt/cord-331193-33cyvidx.txt cache: ./cache/cord-331193-33cyvidx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331193-33cyvidx.txt' === file2bib.sh === id: cord-329493-ueqlhgn0 author: Stadler, Konrad title: SARS — beginning to understand a new virus date: 2003 pages: extension: .txt txt: ./txt/cord-329493-ueqlhgn0.txt cache: ./cache/cord-329493-ueqlhgn0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329493-ueqlhgn0.txt' === file2bib.sh === id: cord-325902-33pxylb3 author: Hemida, Maged Gomaa title: Middle East Respiratory Syndrome Coronavirus and the One Health concept date: 2019-08-22 pages: extension: .txt txt: ./txt/cord-325902-33pxylb3.txt cache: ./cache/cord-325902-33pxylb3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325902-33pxylb3.txt' === file2bib.sh === id: cord-316126-j51dik7f author: Zhang, X. Sophie title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-316126-j51dik7f.txt cache: ./cache/cord-316126-j51dik7f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316126-j51dik7f.txt' === file2bib.sh === id: cord-331472-kd4uxcve author: Shahid, Zainab title: COVID‐19 and Older Adults: What We Know date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-331472-kd4uxcve.txt cache: ./cache/cord-331472-kd4uxcve.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331472-kd4uxcve.txt' === file2bib.sh === id: cord-333682-ktbnrkwh author: Dong, Yunzhu title: Antibodies in the breast milk of a maternal woman with COVID-19 date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-333682-ktbnrkwh.txt cache: ./cache/cord-333682-ktbnrkwh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333682-ktbnrkwh.txt' === file2bib.sh === id: cord-321166-nvphu1fm author: Thomson, Emma C. title: The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-321166-nvphu1fm.txt cache: ./cache/cord-321166-nvphu1fm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321166-nvphu1fm.txt' === file2bib.sh === id: cord-332723-rz1iilsv author: Creager, Hannah M. title: Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2 date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-332723-rz1iilsv.txt cache: ./cache/cord-332723-rz1iilsv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332723-rz1iilsv.txt' === file2bib.sh === id: cord-332448-5fz8ef4f author: Mutnal, M. B. title: Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses date: 2020-05-02 pages: extension: .txt txt: ./txt/cord-332448-5fz8ef4f.txt cache: ./cache/cord-332448-5fz8ef4f.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332448-5fz8ef4f.txt' === file2bib.sh === id: cord-333326-n9ifhw5s author: Wardell, Hanna title: Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-333326-n9ifhw5s.txt cache: ./cache/cord-333326-n9ifhw5s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333326-n9ifhw5s.txt' === file2bib.sh === id: cord-279255-v861kk0i author: Dhama, Kuldeep title: Coronavirus Disease 2019–COVID-19 date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-279255-v861kk0i.txt cache: ./cache/cord-279255-v861kk0i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-279255-v861kk0i.txt' === file2bib.sh === id: cord-330597-nftwj0d5 author: Hopfer, Helmut title: Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues date: 2020-09-27 pages: extension: .txt txt: ./txt/cord-330597-nftwj0d5.txt cache: ./cache/cord-330597-nftwj0d5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330597-nftwj0d5.txt' === file2bib.sh === id: cord-335289-m4u96x2v author: Bhattacharya, Manojit title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach date: 2020-03-05 pages: extension: .txt txt: ./txt/cord-335289-m4u96x2v.txt cache: ./cache/cord-335289-m4u96x2v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335289-m4u96x2v.txt' === file2bib.sh === id: cord-332948-h297ukuu author: Olotu, Fisayo A. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-332948-h297ukuu.txt cache: ./cache/cord-332948-h297ukuu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332948-h297ukuu.txt' === file2bib.sh === id: cord-329010-n0mz098o author: McKee, Dwight L. title: Candidate drugs against SARS-CoV-2 and COVID-19 date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-329010-n0mz098o.txt cache: ./cache/cord-329010-n0mz098o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329010-n0mz098o.txt' === file2bib.sh === id: cord-322913-sq9mq6f1 author: Ciabattini, Annalisa title: Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-322913-sq9mq6f1.txt cache: ./cache/cord-322913-sq9mq6f1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322913-sq9mq6f1.txt' === file2bib.sh === id: cord-321918-9jwma2y6 author: Xiu, Siyu title: Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-321918-9jwma2y6.txt cache: ./cache/cord-321918-9jwma2y6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321918-9jwma2y6.txt' === file2bib.sh === id: cord-325966-0g7a9s5z author: Shih, Hsin-I. title: Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-325966-0g7a9s5z.txt cache: ./cache/cord-325966-0g7a9s5z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325966-0g7a9s5z.txt' === file2bib.sh === id: cord-336057-tj9qcuf8 author: Lv, Yantian title: No intrauterine vertical transmission in pregnancy with COVID-19: a case report date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-336057-tj9qcuf8.txt cache: ./cache/cord-336057-tj9qcuf8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-336057-tj9qcuf8.txt' === file2bib.sh === id: cord-337835-78i6j11i author: Alfaraj, Sarah H. title: The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus date: 2017-02-09 pages: extension: .txt txt: ./txt/cord-337835-78i6j11i.txt cache: ./cache/cord-337835-78i6j11i.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-337835-78i6j11i.txt' === file2bib.sh === id: cord-327997-noqbcxua author: Wu, Kevin E. title: RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-327997-noqbcxua.txt cache: ./cache/cord-327997-noqbcxua.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-327997-noqbcxua.txt' === file2bib.sh === id: cord-335155-x9az3twa author: Qi, Zhen title: Phylogeny of SARS-CoV as inferred from complete genome comparison date: 2003 pages: extension: .txt txt: ./txt/cord-335155-x9az3twa.txt cache: ./cache/cord-335155-x9az3twa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335155-x9az3twa.txt' === file2bib.sh === id: cord-334313-v2syspu6 author: Long, S. Wesley title: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date: 2020-05-03 pages: extension: .txt txt: ./txt/cord-334313-v2syspu6.txt cache: ./cache/cord-334313-v2syspu6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334313-v2syspu6.txt' === file2bib.sh === id: cord-333547-88dkh6xd author: Hasan, Shadi W. title: Detection and Quantification of SARS-CoV-2 RNA in Wastewater and Treated Effluents: Surveillance of COVID-19 Epidemic in the United Arab Emirates date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-333547-88dkh6xd.txt cache: ./cache/cord-333547-88dkh6xd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333547-88dkh6xd.txt' === file2bib.sh === id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-334220-sqvfr31q.txt cache: ./cache/cord-334220-sqvfr31q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334220-sqvfr31q.txt' === file2bib.sh === id: cord-330343-p7a8chn4 author: Kelly-Cirino, Cassandra title: An updated roadmap for MERS-CoV research and product development: focus on diagnostics date: 2019-02-01 pages: extension: .txt txt: ./txt/cord-330343-p7a8chn4.txt cache: ./cache/cord-330343-p7a8chn4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330343-p7a8chn4.txt' === file2bib.sh === id: cord-328395-2cakgmsj author: Oxford, Alexandra E. title: Endothelial Cell Contributions to COVID-19 date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-328395-2cakgmsj.txt cache: ./cache/cord-328395-2cakgmsj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328395-2cakgmsj.txt' === file2bib.sh === id: cord-338775-gh3a0wuf author: Gulersen, Moti title: Histopathological evaluation of placentas after diagnosis of maternal SARS-CoV-2 infection date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-338775-gh3a0wuf.txt cache: ./cache/cord-338775-gh3a0wuf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338775-gh3a0wuf.txt' === file2bib.sh === id: cord-332778-rf47ptj6 author: Vivarelli, Silvia title: Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial? date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-332778-rf47ptj6.txt cache: ./cache/cord-332778-rf47ptj6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-332778-rf47ptj6.txt' === file2bib.sh === id: cord-335652-v98gv5uf author: Salazar, Cecilia title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date: 2020-05-10 pages: extension: .txt txt: ./txt/cord-335652-v98gv5uf.txt cache: ./cache/cord-335652-v98gv5uf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335652-v98gv5uf.txt' === file2bib.sh === id: cord-317952-4oa9hfb4 author: Bourgonje, Arno R. title: Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-317952-4oa9hfb4.txt cache: ./cache/cord-317952-4oa9hfb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317952-4oa9hfb4.txt' === file2bib.sh === id: cord-338923-hc7gagnq author: Jääskeläinen, AJ title: Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-338923-hc7gagnq.txt cache: ./cache/cord-338923-hc7gagnq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338923-hc7gagnq.txt' === file2bib.sh === id: cord-338544-eph89g47 author: Spuntarelli, Valerio title: COVID-19: is it just a lung disease? A case-based review date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-338544-eph89g47.txt cache: ./cache/cord-338544-eph89g47.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338544-eph89g47.txt' === file2bib.sh === id: cord-334976-53cd16w5 author: Jo, Seri title: Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-334976-53cd16w5.txt cache: ./cache/cord-334976-53cd16w5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334976-53cd16w5.txt' === file2bib.sh === id: cord-339859-anatn295 author: Paret, Michal title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress date: 2020-04-17 pages: extension: .txt txt: ./txt/cord-339859-anatn295.txt cache: ./cache/cord-339859-anatn295.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339859-anatn295.txt' === file2bib.sh === id: cord-337430-c2vdnml7 author: Timpka, Toomas title: Sports Health During the SARS-Cov-2 Pandemic date: 2020-05-02 pages: extension: .txt txt: ./txt/cord-337430-c2vdnml7.txt cache: ./cache/cord-337430-c2vdnml7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337430-c2vdnml7.txt' === file2bib.sh === id: cord-328289-3h3kmjlz author: Iadecola, Costantino title: Effects of COVID-19 on the nervous system date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-328289-3h3kmjlz.txt cache: ./cache/cord-328289-3h3kmjlz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328289-3h3kmjlz.txt' === file2bib.sh === id: cord-340049-6rqmc89u author: Salvatori, Giovanni title: SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines date: 2020-06-03 pages: extension: .txt txt: ./txt/cord-340049-6rqmc89u.txt cache: ./cache/cord-340049-6rqmc89u.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340049-6rqmc89u.txt' === file2bib.sh === id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-328003-yovp8squ.txt cache: ./cache/cord-328003-yovp8squ.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328003-yovp8squ.txt' === file2bib.sh === id: cord-338243-njkhwkwk author: Zhang, Dayi title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-338243-njkhwkwk.txt cache: ./cache/cord-338243-njkhwkwk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338243-njkhwkwk.txt' === file2bib.sh === id: cord-339762-lh8czr0a author: Ng, Dianna L. title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 date: 2016-03-31 pages: extension: .txt txt: ./txt/cord-339762-lh8czr0a.txt cache: ./cache/cord-339762-lh8czr0a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339762-lh8czr0a.txt' === file2bib.sh === id: cord-333498-d25qfq0f author: Chitranshi, Nitin title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-333498-d25qfq0f.txt cache: ./cache/cord-333498-d25qfq0f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333498-d25qfq0f.txt' === file2bib.sh === id: cord-335122-8s3bcyo8 author: Marshall, Steve title: COVID-19: What do we know? date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-335122-8s3bcyo8.txt cache: ./cache/cord-335122-8s3bcyo8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335122-8s3bcyo8.txt' === file2bib.sh === id: cord-334550-xb0alubj author: Samaddar, Arghadip title: The Enigma of Low COVID-19 Fatality Rate in India date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-334550-xb0alubj.txt cache: ./cache/cord-334550-xb0alubj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334550-xb0alubj.txt' === file2bib.sh === id: cord-341254-xnj6slby author: Li, Hua title: A new and rapid approach for detecting COVID‐19 based on S1 protein fragments date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-341254-xnj6slby.txt cache: ./cache/cord-341254-xnj6slby.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341254-xnj6slby.txt' === file2bib.sh === id: cord-343827-jo61t3m0 author: Qian, Qun title: Direct evidence of active SARS-CoV-2 replication in the intestine date: 2020-07-08 pages: extension: .txt txt: ./txt/cord-343827-jo61t3m0.txt cache: ./cache/cord-343827-jo61t3m0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343827-jo61t3m0.txt' === file2bib.sh === id: cord-338468-c0jv3i1t author: Kanduc, Darja title: From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-338468-c0jv3i1t.txt cache: ./cache/cord-338468-c0jv3i1t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338468-c0jv3i1t.txt' === file2bib.sh === id: cord-331094-22366b81 author: Ianevski, Aleksandr title: Potential Antiviral Options against SARS-CoV-2 Infection date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-331094-22366b81.txt cache: ./cache/cord-331094-22366b81.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331094-22366b81.txt' === file2bib.sh === id: cord-333703-1ku3jc9s author: Kraus, Aurora title: A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date: 2020-11-08 pages: extension: .txt txt: ./txt/cord-333703-1ku3jc9s.txt cache: ./cache/cord-333703-1ku3jc9s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333703-1ku3jc9s.txt' === file2bib.sh === id: cord-343196-vlwzzrgc author: Kiambi, Stella title: Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017 date: 2018-11-28 pages: extension: .txt txt: ./txt/cord-343196-vlwzzrgc.txt cache: ./cache/cord-343196-vlwzzrgc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343196-vlwzzrgc.txt' === file2bib.sh === id: cord-337089-ksh62ni0 author: Salajegheh Tazerji, Sina title: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-337089-ksh62ni0.txt cache: ./cache/cord-337089-ksh62ni0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337089-ksh62ni0.txt' === file2bib.sh === id: cord-328000-i9tzr13z author: Cockrell, Adam S. title: Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice date: 2018-07-24 pages: extension: .txt txt: ./txt/cord-328000-i9tzr13z.txt cache: ./cache/cord-328000-i9tzr13z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328000-i9tzr13z.txt' === file2bib.sh === id: cord-334773-yw2qgv13 author: Lisco, Giuseppe title: Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-334773-yw2qgv13.txt cache: ./cache/cord-334773-yw2qgv13.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334773-yw2qgv13.txt' === file2bib.sh === id: cord-337712-ylqgraos author: Heinz, Franz X. title: Profile of SARS-CoV-2 date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-337712-ylqgraos.txt cache: ./cache/cord-337712-ylqgraos.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337712-ylqgraos.txt' === file2bib.sh === id: cord-339009-wcoch07b author: File, Thomas M. title: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy date: 2012-08-23 pages: extension: .txt txt: ./txt/cord-339009-wcoch07b.txt cache: ./cache/cord-339009-wcoch07b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339009-wcoch07b.txt' === file2bib.sh === id: cord-341234-2zgfcrwc author: Hallak, Jorge title: Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-341234-2zgfcrwc.txt cache: ./cache/cord-341234-2zgfcrwc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341234-2zgfcrwc.txt' === file2bib.sh === id: cord-343317-97n1j0jj author: Duan, Xiaohua title: Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date: 2020-05-02 pages: extension: .txt txt: ./txt/cord-343317-97n1j0jj.txt cache: ./cache/cord-343317-97n1j0jj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343317-97n1j0jj.txt' === file2bib.sh === id: cord-344266-ug2uew71 author: Crema, E. title: The SARS-COV-2 outbreak around the Amazon rainforest: the relevance of the airborne transmission date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-344266-ug2uew71.txt cache: ./cache/cord-344266-ug2uew71.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344266-ug2uew71.txt' === file2bib.sh === id: cord-336150-l8w7xk0b author: Rathore, Jitendra Singh title: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: an overview date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-336150-l8w7xk0b.txt cache: ./cache/cord-336150-l8w7xk0b.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336150-l8w7xk0b.txt' === file2bib.sh === id: cord-339344-qd73h1ie author: Simon, David title: Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-339344-qd73h1ie.txt cache: ./cache/cord-339344-qd73h1ie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339344-qd73h1ie.txt' === file2bib.sh === id: cord-337812-arivkkj0 author: Chu, Ling-Hon Matthew title: Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry date: 2006-03-07 pages: extension: .txt txt: ./txt/cord-337812-arivkkj0.txt cache: ./cache/cord-337812-arivkkj0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337812-arivkkj0.txt' === file2bib.sh === id: cord-348192-ibohbjfb author: Odih, Erkison E. title: Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-348192-ibohbjfb.txt cache: ./cache/cord-348192-ibohbjfb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348192-ibohbjfb.txt' === file2bib.sh === id: cord-340305-jtvn9tlm author: Cimolai, Nevio title: A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19 date: 2020-09-19 pages: extension: .txt txt: ./txt/cord-340305-jtvn9tlm.txt cache: ./cache/cord-340305-jtvn9tlm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340305-jtvn9tlm.txt' === file2bib.sh === id: cord-348384-8cvt1fo6 author: Butsashvili, M. title: Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-348384-8cvt1fo6.txt cache: ./cache/cord-348384-8cvt1fo6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-348384-8cvt1fo6.txt' === file2bib.sh === id: cord-346960-3empldlo author: Plebani, M. title: Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-346960-3empldlo.txt cache: ./cache/cord-346960-3empldlo.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-346960-3empldlo.txt' === file2bib.sh === id: cord-337105-jlmh79qv author: Jacob, Fadi title: Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-337105-jlmh79qv.txt cache: ./cache/cord-337105-jlmh79qv.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337105-jlmh79qv.txt' === file2bib.sh === id: cord-335137-5qt286kc author: Chatterjee, Swapan K. title: Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19 date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-335137-5qt286kc.txt cache: ./cache/cord-335137-5qt286kc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335137-5qt286kc.txt' === file2bib.sh === id: cord-339665-nwwutduy author: Patel, Ami title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-339665-nwwutduy.txt cache: ./cache/cord-339665-nwwutduy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339665-nwwutduy.txt' === file2bib.sh === id: cord-327063-ea7a1xfl author: Dhama, Kuldeep title: SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus date: 2020-08-02 pages: extension: .txt txt: ./txt/cord-327063-ea7a1xfl.txt cache: ./cache/cord-327063-ea7a1xfl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327063-ea7a1xfl.txt' === file2bib.sh === id: cord-343517-vf32wxkx author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-343517-vf32wxkx.txt cache: ./cache/cord-343517-vf32wxkx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-343517-vf32wxkx.txt' === file2bib.sh === id: cord-342569-ja96xfns author: Azer, Samy A. title: COVID-19: Pathophysiology, diagnosis, complications and Investigational therapeutics date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-342569-ja96xfns.txt cache: ./cache/cord-342569-ja96xfns.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342569-ja96xfns.txt' === file2bib.sh === id: cord-332992-8rmqg4rf author: de Vries, A. A. F. title: SARS-CoV-2/COVID-19: a primer for cardiologists date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-332992-8rmqg4rf.txt cache: ./cache/cord-332992-8rmqg4rf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332992-8rmqg4rf.txt' === file2bib.sh === id: cord-342383-ckswlo9o author: Pawlowski, C. title: Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-342383-ckswlo9o.txt cache: ./cache/cord-342383-ckswlo9o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342383-ckswlo9o.txt' === file2bib.sh === id: cord-345929-z7yfegr5 author: Thakur, Suman S. title: Proteomics and Its Application in Pandemic Diseases date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-345929-z7yfegr5.txt cache: ./cache/cord-345929-z7yfegr5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-345929-z7yfegr5.txt' === file2bib.sh === id: cord-338205-sy91rnse author: Li, Chenxi title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-338205-sy91rnse.txt cache: ./cache/cord-338205-sy91rnse.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338205-sy91rnse.txt' === file2bib.sh === id: cord-329190-kv9n2qj3 author: Rabaan, Ali A. title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date: 2017-09-01 pages: extension: .txt txt: ./txt/cord-329190-kv9n2qj3.txt cache: ./cache/cord-329190-kv9n2qj3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329190-kv9n2qj3.txt' === file2bib.sh === id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-346819-11fkgzaa.txt cache: ./cache/cord-346819-11fkgzaa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346819-11fkgzaa.txt' === file2bib.sh === id: cord-340516-9dfaqsv7 author: Moore, Anne C. title: Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-340516-9dfaqsv7.txt cache: ./cache/cord-340516-9dfaqsv7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340516-9dfaqsv7.txt' === file2bib.sh === id: cord-343528-5283jsnu author: Zhang, Zhao title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date: 2016-05-04 pages: extension: .txt txt: ./txt/cord-343528-5283jsnu.txt cache: ./cache/cord-343528-5283jsnu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343528-5283jsnu.txt' === file2bib.sh === id: cord-326017-qw4qynqv author: Laskar, Partha title: “Tomorrow Never Dies”: Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-326017-qw4qynqv.txt cache: ./cache/cord-326017-qw4qynqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326017-qw4qynqv.txt' === file2bib.sh === id: cord-340042-intxyu46 author: Chaudhry, Sundas Nasir title: New insight on possible vaccine development against SARS-CoV-2 date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-340042-intxyu46.txt cache: ./cache/cord-340042-intxyu46.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340042-intxyu46.txt' === file2bib.sh === id: cord-338973-73a7uvyz author: Xu, Jiabao title: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date: 2020-02-22 pages: extension: .txt txt: ./txt/cord-338973-73a7uvyz.txt cache: ./cache/cord-338973-73a7uvyz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-338973-73a7uvyz.txt' === file2bib.sh === id: cord-347706-r0rs3ls1 author: Roberts, Anjeanette title: Animal Models for Sars date: 2006 pages: extension: .txt txt: ./txt/cord-347706-r0rs3ls1.txt cache: ./cache/cord-347706-r0rs3ls1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347706-r0rs3ls1.txt' === file2bib.sh === id: cord-343302-g9vcchrh author: Agrawal, Anurodh Shankar title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date: 2016-08-19 pages: extension: .txt txt: ./txt/cord-343302-g9vcchrh.txt cache: ./cache/cord-343302-g9vcchrh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343302-g9vcchrh.txt' === file2bib.sh === id: cord-348821-2u6ki9dv author: Xu, Ping title: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. date: 2020-03-10 pages: extension: .txt txt: ./txt/cord-348821-2u6ki9dv.txt cache: ./cache/cord-348821-2u6ki9dv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348821-2u6ki9dv.txt' === file2bib.sh === id: cord-342796-f7n8sxbu author: Stowe, J. title: Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-342796-f7n8sxbu.txt cache: ./cache/cord-342796-f7n8sxbu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342796-f7n8sxbu.txt' === file2bib.sh === id: cord-334564-bqh9jkds author: Raony, Ícaro title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-334564-bqh9jkds.txt cache: ./cache/cord-334564-bqh9jkds.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334564-bqh9jkds.txt' === file2bib.sh === id: cord-348301-bk80pps9 author: Wahl, Angela title: Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-348301-bk80pps9.txt cache: ./cache/cord-348301-bk80pps9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348301-bk80pps9.txt' === file2bib.sh === id: cord-342538-5bwsm290 author: Izquierdo Lara, R. W. title: Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-342538-5bwsm290.txt cache: ./cache/cord-342538-5bwsm290.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342538-5bwsm290.txt' === file2bib.sh === id: cord-342902-y1v8wzxq author: Yuan, Shuofeng title: Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-342902-y1v8wzxq.txt cache: ./cache/cord-342902-y1v8wzxq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342902-y1v8wzxq.txt' === file2bib.sh === id: cord-346987-fbqqf00i author: Guo, Yongwen title: Controls of SARS-CoV-2 transmission in orthodontic practice date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-346987-fbqqf00i.txt cache: ./cache/cord-346987-fbqqf00i.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346987-fbqqf00i.txt' === file2bib.sh === id: cord-336775-d4hi9myk author: Kirtipal, Nikhil title: From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-336775-d4hi9myk.txt cache: ./cache/cord-336775-d4hi9myk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336775-d4hi9myk.txt' === file2bib.sh === id: cord-347767-aq9niccc author: Zhao, Jie title: Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-347767-aq9niccc.txt cache: ./cache/cord-347767-aq9niccc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347767-aq9niccc.txt' === file2bib.sh === id: cord-348696-86nbwon2 author: Güemes-Villahoz, Noemi title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-348696-86nbwon2.txt cache: ./cache/cord-348696-86nbwon2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348696-86nbwon2.txt' === file2bib.sh === id: cord-350557-7i7122zi author: Rawlings, Stephen A title: No Evidence of SARS-CoV-2 Seminal Shedding Despite SARS-CoV-2 Persistence in the Upper Respiratory Tract date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-350557-7i7122zi.txt cache: ./cache/cord-350557-7i7122zi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350557-7i7122zi.txt' === file2bib.sh === id: cord-345356-gn1iwis0 author: Glebov, Oleg O. title: Understanding SARS‐CoV‐2 endocytosis for COVID‐19 drug repurposing date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-345356-gn1iwis0.txt cache: ./cache/cord-345356-gn1iwis0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345356-gn1iwis0.txt' === file2bib.sh === id: cord-347734-0z2kin6r author: Armann, J. P. title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-347734-0z2kin6r.txt cache: ./cache/cord-347734-0z2kin6r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347734-0z2kin6r.txt' === file2bib.sh === id: cord-348899-vynk8q8c author: Jo, Seri title: Inhibition of SARS-CoV 3CL protease by flavonoids date: 2019-11-14 pages: extension: .txt txt: ./txt/cord-348899-vynk8q8c.txt cache: ./cache/cord-348899-vynk8q8c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348899-vynk8q8c.txt' === file2bib.sh === id: cord-350352-wgppovfx author: Temmam, Sarah title: Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-350352-wgppovfx.txt cache: ./cache/cord-350352-wgppovfx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-350352-wgppovfx.txt' === file2bib.sh === id: cord-350505-uh8r2vyz author: Kalantar-Zadeh, Kourosh title: Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-350505-uh8r2vyz.txt cache: ./cache/cord-350505-uh8r2vyz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350505-uh8r2vyz.txt' === file2bib.sh === id: cord-350451-lf27iuwk author: Benedetti, Francesca title: SARS‐CoV‐2: March toward adaptation date: 2020-07-11 pages: extension: .txt txt: ./txt/cord-350451-lf27iuwk.txt cache: ./cache/cord-350451-lf27iuwk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350451-lf27iuwk.txt' === file2bib.sh === id: cord-351169-y91fdf66 author: Phillips, Lia title: Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia date: 2020-09-14 pages: extension: .txt txt: ./txt/cord-351169-y91fdf66.txt cache: ./cache/cord-351169-y91fdf66.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351169-y91fdf66.txt' === file2bib.sh === id: cord-350737-nrtrhq1f author: Chen, Xinchun title: Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome date: 2004-04-01 pages: extension: .txt txt: ./txt/cord-350737-nrtrhq1f.txt cache: ./cache/cord-350737-nrtrhq1f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350737-nrtrhq1f.txt' === file2bib.sh === id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-338436-0z828org.txt cache: ./cache/cord-338436-0z828org.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338436-0z828org.txt' === file2bib.sh === id: cord-349659-6drnriun author: Grant, Benjamin D. title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-349659-6drnriun.txt cache: ./cache/cord-349659-6drnriun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349659-6drnriun.txt' === file2bib.sh === id: cord-349643-jtx7ni9b author: Uyeki, Timothy M. title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus date: 2016-07-17 pages: extension: .txt txt: ./txt/cord-349643-jtx7ni9b.txt cache: ./cache/cord-349643-jtx7ni9b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349643-jtx7ni9b.txt' === file2bib.sh === id: cord-341287-i1hyk962 author: Smith, Trevor R. F. title: Immunogenicity of a DNA vaccine candidate for COVID-19 date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-341287-i1hyk962.txt cache: ./cache/cord-341287-i1hyk962.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341287-i1hyk962.txt' === file2bib.sh === id: cord-350855-gofzhff7 author: Hou, Yixuan J. title: SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-350855-gofzhff7.txt cache: ./cache/cord-350855-gofzhff7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350855-gofzhff7.txt' === file2bib.sh === id: cord-342220-lrqt2gcw author: Dearlove, Bethany title: A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-342220-lrqt2gcw.txt cache: ./cache/cord-342220-lrqt2gcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342220-lrqt2gcw.txt' === file2bib.sh === id: cord-352909-s11tpfoq author: Sun, Zhiping title: Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-352909-s11tpfoq.txt cache: ./cache/cord-352909-s11tpfoq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352909-s11tpfoq.txt' === file2bib.sh === id: cord-353209-qkhfp66l author: Steiner, Daniel J. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-353209-qkhfp66l.txt cache: ./cache/cord-353209-qkhfp66l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353209-qkhfp66l.txt' === file2bib.sh === id: cord-349262-gnqbyc6t author: Hemida, Maged Gomaa title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-349262-gnqbyc6t.txt cache: ./cache/cord-349262-gnqbyc6t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349262-gnqbyc6t.txt' === file2bib.sh === id: cord-345381-9cckppk2 author: Klimek, Ludger title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) date: 2020-09-07 pages: extension: .txt txt: ./txt/cord-345381-9cckppk2.txt cache: ./cache/cord-345381-9cckppk2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345381-9cckppk2.txt' === file2bib.sh === id: cord-346777-zmmnn9b2 author: Lester, Sandra title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies date: 2019-09-11 pages: extension: .txt txt: ./txt/cord-346777-zmmnn9b2.txt cache: ./cache/cord-346777-zmmnn9b2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346777-zmmnn9b2.txt' === file2bib.sh === id: cord-356166-fpno9zg5 author: Miyakawa, Kei title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-356166-fpno9zg5.txt cache: ./cache/cord-356166-fpno9zg5.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356166-fpno9zg5.txt' === file2bib.sh === id: cord-341453-9yrvjlpx author: Clay, Candice C title: Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses date: 2014-03-19 pages: extension: .txt txt: ./txt/cord-341453-9yrvjlpx.txt cache: ./cache/cord-341453-9yrvjlpx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341453-9yrvjlpx.txt' === file2bib.sh === id: cord-353293-vjdwh19x author: nan title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach date: 2020-06-11 pages: extension: .txt txt: ./txt/cord-353293-vjdwh19x.txt cache: ./cache/cord-353293-vjdwh19x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353293-vjdwh19x.txt' === file2bib.sh === id: cord-349117-xfir3m5p author: Hyseni, Inesa title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-349117-xfir3m5p.txt cache: ./cache/cord-349117-xfir3m5p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349117-xfir3m5p.txt' === file2bib.sh === id: cord-353524-3w970ycx author: Dömling, Alexander title: Chemistry and Biology of SARS-CoV-2 date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-353524-3w970ycx.txt cache: ./cache/cord-353524-3w970ycx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-353524-3w970ycx.txt' === file2bib.sh === id: cord-344714-0cam9ipf author: Russo, Maria title: Roles of flavonoids against coronavirus infection date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-344714-0cam9ipf.txt cache: ./cache/cord-344714-0cam9ipf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-344714-0cam9ipf.txt' === file2bib.sh === id: cord-354597-xubsodnk author: Carvalho, Alexandre title: SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease date: 2020-04-17 pages: extension: .txt txt: ./txt/cord-354597-xubsodnk.txt cache: ./cache/cord-354597-xubsodnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354597-xubsodnk.txt' === file2bib.sh === id: cord-351011-v4zmksio author: Golden, Joseph W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-351011-v4zmksio.txt cache: ./cache/cord-351011-v4zmksio.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351011-v4zmksio.txt' === file2bib.sh === id: cord-350015-mg5wiihj author: Chen, Yiyin title: Aging in COVID-19: Vulnerability, immunity and intervention date: 2020-10-31 pages: extension: .txt txt: ./txt/cord-350015-mg5wiihj.txt cache: ./cache/cord-350015-mg5wiihj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350015-mg5wiihj.txt' === file2bib.sh === id: cord-350903-nwagvvc5 author: Softic, Laurent title: Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025) date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-350903-nwagvvc5.txt cache: ./cache/cord-350903-nwagvvc5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350903-nwagvvc5.txt' === file2bib.sh === id: cord-354398-f3cg8gi1 author: Al-Saud, Haya title: Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing date: 2020-09-20 pages: extension: .txt txt: ./txt/cord-354398-f3cg8gi1.txt cache: ./cache/cord-354398-f3cg8gi1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354398-f3cg8gi1.txt' === file2bib.sh === id: cord-354394-zojhdnlu author: Wang, Wei-Kung title: Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis date: 2004-07-17 pages: extension: .txt txt: ./txt/cord-354394-zojhdnlu.txt cache: ./cache/cord-354394-zojhdnlu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354394-zojhdnlu.txt' === file2bib.sh === id: cord-353392-rqeultbq author: Kumar, Govindarajan Venkat title: A short review on antibody therapy for COVID-19 date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-353392-rqeultbq.txt cache: ./cache/cord-353392-rqeultbq.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353392-rqeultbq.txt' === file2bib.sh === id: cord-352123-0bflqj1c author: Csiszar, Anna title: Companion animals likely do not spread COVID-19 but may get infected themselves date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-352123-0bflqj1c.txt cache: ./cache/cord-352123-0bflqj1c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-352123-0bflqj1c.txt' === file2bib.sh === id: cord-347460-9vechh4x author: Chang, Feng-Yee title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-347460-9vechh4x.txt cache: ./cache/cord-347460-9vechh4x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347460-9vechh4x.txt' === file2bib.sh === id: cord-353777-t8q99tlq author: Jia, Yong title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-353777-t8q99tlq.txt cache: ./cache/cord-353777-t8q99tlq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353777-t8q99tlq.txt' === file2bib.sh === id: cord-349682-kpg0vley author: Ojha, Probir Kumar title: Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-349682-kpg0vley.txt cache: ./cache/cord-349682-kpg0vley.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349682-kpg0vley.txt' === file2bib.sh === id: cord-350959-bsbz3a1l author: Dovey, Zachary title: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-350959-bsbz3a1l.txt cache: ./cache/cord-350959-bsbz3a1l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350959-bsbz3a1l.txt' === file2bib.sh === id: cord-350992-l6l24pco author: Roldan, Eugenia Quiros title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-350992-l6l24pco.txt cache: ./cache/cord-350992-l6l24pco.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350992-l6l24pco.txt' === file2bib.sh === id: cord-345371-pjbviagq author: Lisi, Lucia title: Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2 date: 2020-07-23 pages: extension: .txt txt: ./txt/cord-345371-pjbviagq.txt cache: ./cache/cord-345371-pjbviagq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345371-pjbviagq.txt' === file2bib.sh === id: cord-351649-87g7g5au author: Haagmans, Bart L. title: SARS date: 2009-01-30 pages: extension: .txt txt: ./txt/cord-351649-87g7g5au.txt cache: ./cache/cord-351649-87g7g5au.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351649-87g7g5au.txt' === file2bib.sh === id: cord-351115-dy81dtnk author: Wang, Chen title: Identification of evolutionarily stable sites across the SARS-CoV-2 proteome date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-351115-dy81dtnk.txt cache: ./cache/cord-351115-dy81dtnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351115-dy81dtnk.txt' === file2bib.sh === id: cord-337825-ujq9mxk7 author: Chen, Bin title: Overview of lethal human coronaviruses date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-337825-ujq9mxk7.txt cache: ./cache/cord-337825-ujq9mxk7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337825-ujq9mxk7.txt' === file2bib.sh === id: cord-351525-306syrrn author: Yang, Yong-Le title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission date: 2019-11-26 pages: extension: .txt txt: ./txt/cord-351525-306syrrn.txt cache: ./cache/cord-351525-306syrrn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351525-306syrrn.txt' === file2bib.sh === id: cord-352562-qfb478sf author: Yamamoto, Lidia title: SARS-CoV-2 infections with emphasis on pediatric patients: a narrative review date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-352562-qfb478sf.txt cache: ./cache/cord-352562-qfb478sf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352562-qfb478sf.txt' === file2bib.sh === id: cord-353826-owoec2ud author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-353826-owoec2ud.txt cache: ./cache/cord-353826-owoec2ud.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353826-owoec2ud.txt' === file2bib.sh === id: cord-347351-emdj66vj author: Kampf, Günter title: Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-347351-emdj66vj.txt cache: ./cache/cord-347351-emdj66vj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347351-emdj66vj.txt' === file2bib.sh === id: cord-356009-emn2w8if author: Roshandel, M. R. title: What Specimen Urologists Should Be Most Concerned About ? A Systematic Review and Meta-Analysis date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-356009-emn2w8if.txt cache: ./cache/cord-356009-emn2w8if.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-356009-emn2w8if.txt' === file2bib.sh === id: cord-353704-lfndq85x author: Ye, Zi-Wei title: Zoonotic origins of human coronaviruses date: 2020-03-15 pages: extension: .txt txt: ./txt/cord-353704-lfndq85x.txt cache: ./cache/cord-353704-lfndq85x.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353704-lfndq85x.txt' === file2bib.sh === id: cord-355567-60sfv60p author: Azuma, Kenichi title: Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-355567-60sfv60p.txt cache: ./cache/cord-355567-60sfv60p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355567-60sfv60p.txt' === file2bib.sh === id: cord-342756-rgm9ffpk author: Senger, Mario Roberto title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-342756-rgm9ffpk.txt cache: ./cache/cord-342756-rgm9ffpk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342756-rgm9ffpk.txt' === file2bib.sh === id: cord-353484-q7d0ysbo author: Liu, Xue title: COVID-19: Progress in diagnostics, therapy and vaccination date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-353484-q7d0ysbo.txt cache: ./cache/cord-353484-q7d0ysbo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353484-q7d0ysbo.txt' === file2bib.sh === id: cord-354824-7fdcu2f0 author: Wu, Renyi title: An Update on Current Therapeutic Drugs Treating COVID-19 date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-354824-7fdcu2f0.txt cache: ./cache/cord-354824-7fdcu2f0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354824-7fdcu2f0.txt' === file2bib.sh === id: cord-352230-8mazd3eu author: Beeraka, Narasimha M. title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-352230-8mazd3eu.txt cache: ./cache/cord-352230-8mazd3eu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352230-8mazd3eu.txt' === file2bib.sh === id: cord-346539-kxnrf5g5 author: Riggioni, Carmen title: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 date: 2020-06-14 pages: extension: .txt txt: ./txt/cord-346539-kxnrf5g5.txt cache: ./cache/cord-346539-kxnrf5g5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346539-kxnrf5g5.txt' Que is empty; done keyword-cov-cord === reduce.pl bib === id = cord-024133-zv0ysi8m author = Saxena, Shailendra K. title = Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) date = 2020-04-30 pages = extension = .txt mime = text/plain words = 2220 sentences = 142 flesch = 49 summary = On 11 March 2020, the World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic that causes novel coronavirus disease 2019 (COVID-19) (World Health Organization 2020a). In addition, the scientific fraternity worldwide has been continuously working on COVID-19 from the beginning by publishing the genome and developing highly specific diagnostic tools for the detection of SARS-CoV-2 infection. There is no specific treatment available for SARS-CoV-2 and the current treatment relies on supportive care of the infected patients (Centre for Disease Control and Prevention 2020b). Fig. 1.3 Steps needed to be taken by COVID-19 patients in order to prevent the spread of SARS-CoV-2 infection Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Centre for Disease Control and Prevention (2020b) Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). cache = ./cache/cord-024133-zv0ysi8m.txt txt = ./txt/cord-024133-zv0ysi8m.txt === reduce.pl bib === id = cord-025119-201ac32t author = Salman, Saad title = Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date = 2020-05-21 pages = extension = .txt mime = text/plain words = 3144 sentences = 162 flesch = 37 summary = Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Here, we analyzed different medicinal compounds using a virtual screening method to obtain promising inhibitors for these viral proteins that could be further utilized for SARS-COV-2 treatment. More than 300 medicinal compounds with immunomodulatory and antiviral activity were added to the Raccoon2 plugin of Autodock vina to perform virtual screening to obtain promising inhibitors for SARS-COV-2 proteins. This study aimed to obtain novel drug candidates that have the capability to interact with the active site of all of these viral proteins and should possess efficient pharmacokinetic profile with low toxicity to ensure safety during administration. • Docking interaction of immunomodulatory medicinal compounds library filtered six promising medicinal compounds against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) viral proteins. cache = ./cache/cord-025119-201ac32t.txt txt = ./txt/cord-025119-201ac32t.txt === reduce.pl bib === id = cord-029813-o2uzcuai author = Rusconi, Stefano title = COVID-19: studying the global pandemic – foreword date = 2020-07-27 pages = extension = .txt mime = text/plain words = 2723 sentences = 131 flesch = 43 summary = This special issue of Future Virology contains nine articles on diverse aspects of the COVID-19 pandemic and its causative agent, SARS-CoV-2. The topics range from basic virology on coronavirus evolution and replication to identification of repurposed therapeutics for clinical testing to public health issues including the conundrums of asymptomatic viral transmission and risks to homeless populations. The Commentary by Parvez [1] briefly reviews the detection of SARS-CoV-2 RNA in fecal samples, including its persistence, and the finding of gastrointestinal complaints in a minority of hospitalized patients. While it is clear that this phytochemical has multiple pharmacological activities, as reviewed previously [10] , this in silico report does not provide biologic data on rutin's possible effects in SARS-CoV-2 infection. Detection of relatively high SARS-CoV-2 RNA loads in upper respiratory tract samples has been reported in both presymptomatic (late incubation period) and truly asymptomatic infected persons. Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection cache = ./cache/cord-029813-o2uzcuai.txt txt = ./txt/cord-029813-o2uzcuai.txt === reduce.pl bib === id = cord-124012-5zxkd2jy author = Schwab, Patrick title = predCOVID-19: A Systematic Study of Clinical Predictive Models for Coronavirus Disease 2019 date = 2020-05-17 pages = extension = .txt mime = text/plain words = 5098 sentences = 247 flesch = 38 summary = Here, we study clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test, require hospitalisation or intensive care. In addition, [48] performed a cohort study for clinical and laboratory predictors of COVID-19 related inhospital mortality that identified baseline neutrophil count, age Fig. 2 : The presented multistage machine-learning pipeline consists of preprocessing (light purple) the input data x, developing multiple candidate models using the given dataset (orange), selecting the best candidate model for evaluation (blue), and evaluating the selected best model's outputsŷ. Owing to the recent emergence of SARS-CoV-2, there currently exists, to the best of our knowledge, no prior systematic study on clinical predictive models that predict likelihood of a positive SARS-CoV-2 test, hospital and intensive care unit admission from clinical, demographic and blood analysis data that accounts for the missingness that is characteristic for the clinical setting. cache = ./cache/cord-124012-5zxkd2jy.txt txt = ./txt/cord-124012-5zxkd2jy.txt === reduce.pl bib === id = cord-031079-9lxhvyyb author = Chen, Li title = The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review date = 2020-07-27 pages = extension = .txt mime = text/plain words = 5660 sentences = 354 flesch = 47 summary = CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which is mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular system. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to be further elucidated. CQ and its more soluble and less toxic metabolite HCQ are primarily used for prophylaxis and treatment of malaria, but they have also been reported to effectively inhibit the effects of certain viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N. 40, 41 Several studies have reported that 3% to 29% of COVID-19 patients develop acute respiratory distress syndrome (ARDS) which is a common complication and cause of death as a result of SARS-CoV-2 infection. cache = ./cache/cord-031079-9lxhvyyb.txt txt = ./txt/cord-031079-9lxhvyyb.txt === reduce.pl bib === id = cord-009476-4emc4o6n author = Madani, Tariq A title = Case definition and management of patients with MERS coronavirus in Saudi Arabia date = 2014-09-22 pages = extension = .txt mime = text/plain words = 1014 sentences = 47 flesch = 36 summary = 16 outbreak and prevent human-to-human and animalto-human transmission; an appropriate management algorithm, including best-practice guidelines for accurate diagnosis, infection control, intensive care, emergency medicine, and treatment; prioritise research related to the MERS-CoV outbreak such as case-control and cohort studies, seroprevalence studies, and clinical trials; and to eff ectively monitor outbreak control activities. 2 The new case defi nition (appendix) was developed based on reported health-care-associated MERS-CoV pneumonia (added as category 2 in the new case defi nition) and non-respiratory characteristics of patients with confi rmed infection who fi rst presented with acute febrile dengue-like illness with body aches, leucopenia, and thrombocytopenia (added as category 3). WHO Revised interim case defi nition for reporting to WHO-Middle East respiratory syndrome coronavirus (MERS-CoV): as of First confi rmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and Public Health Authorities cache = ./cache/cord-009476-4emc4o6n.txt txt = ./txt/cord-009476-4emc4o6n.txt === reduce.pl bib === id = cord-257399-p6of5fno author = Gentry, Chris A title = Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study date = 2020-09-21 pages = extension = .txt mime = text/plain words = 4529 sentences = 196 flesch = 42 summary = METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. We aimed to examine whether patients with rheuma tological conditions receiving chronic hydroxy chloroquine therapy are at less risk of developing SARS-CoV-2 infection compared with a propensity-matched group of patients not receiving hydroxychloroquine. Our study takes advantage of a setting in which a specific group of patients has been receiving chronic hydroxy chloroquine over several months to years as a novel virus emerges among the population, setting up an ideal premise to test the hypothesis that hydroxychloroquine might be effective in preventing SARS-CoV-2 infection. cache = ./cache/cord-257399-p6of5fno.txt txt = ./txt/cord-257399-p6of5fno.txt === reduce.pl bib === id = cord-193489-u6ewlh16 author = Wang, Rui title = Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date = 2020-04-29 pages = extension = .txt mime = text/plain words = 6066 sentences = 419 flesch = 62 summary = Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. Genetic identification and characterization of the geographic distribution, intercontinental evolution, and global trends of SARS-CoV-2 is the most efficient approach for studying COVID-19 genomic epidemiology and offer the molecular foundation for region-specific SARS-CoV-2 vaccine design, drug discovery, and diagnostic development [10] . We use K-means methods to cluster SARS-CoV-2 mutations, which provides the updated molecular information for the region-specific design of vaccines, drugs, and diagnoses. Table 5 presents the statistics of single mutations on various SARS-CoV-2 proteins that occurred in the recorded genomes between January 5, 2020, and April 24, 2020. Specifically, nucleocapsid protein has both the highest number of mutations per residues of 0.56 and the highest h-index of 27, suggesting that it is the most non-conservative protein in SARS-CoV-2 genomes. cache = ./cache/cord-193489-u6ewlh16.txt txt = ./txt/cord-193489-u6ewlh16.txt === reduce.pl bib === === reduce.pl bib === id = cord-158628-71n1tgrw author = Russo, Giulia title = In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform date = 2020-05-05 pages = extension = .txt mime = text/plain words = 5596 sentences = 296 flesch = 50 summary = Recently, specific findings about the genome sequencing of SARS-CoV-2 in different countries where cases of infection were registered, revealed its relative intrinsic genomic variability, its virus dynamics and the related host response mechanisms, unveiling interesting knowledge useful for the formulation of innovative strategies for preventive vaccination. Specifically, SARS-CoV-2 sequencing along with its relative intrinsic genomic variability [10] , the presence of minority variants generated during SARS-CoV-2 replication [11] , the involved cellular factors that favors SARS-CoV-2 cell entry [12] , the timing in which viral load peaks (during the first week of illness), its gradual decline (over the second week) and the increasing of both IgG and IgM antibodies (around day 10 after symptom onset) represent some of the relevant insights so far delineated and considered by research community about SARS-CoV-2 virus [13] . UISS is an immune system simulation platform that was designed to be applied to several and different scenarios, especially to carry on in silico trials to predict the efficacy of a specific prophylactic or therapeutic vaccine against a particular disease. cache = ./cache/cord-158628-71n1tgrw.txt txt = ./txt/cord-158628-71n1tgrw.txt === reduce.pl bib === id = cord-015503-j99cgsjt author = Tang, Xiaolu title = On the origin and continuing evolution of SARS-CoV-2 date = 2020-03-03 pages = extension = .txt mime = text/plain words = 5243 sentences = 292 flesch = 59 summary = Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Further, the genomic sequences of SARS-CoV-2 viruses isolated from a number of patients share sequence identity higher than 99.9%, suggesting a very recent host shift into humans [1] [2] [3] . cache = ./cache/cord-015503-j99cgsjt.txt txt = ./txt/cord-015503-j99cgsjt.txt === reduce.pl bib === id = cord-252389-xrdbmosj author = Kumar, Mukesh title = Neurological manifestations and comorbidity associated with COVID-19: an overview date = 2020-10-14 pages = extension = .txt mime = text/plain words = 5447 sentences = 265 flesch = 41 summary = In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, exploring the neurologic manifestations associated with COVID-19 is urgently required for better understanding the SARS-CoV-2 brain infections, inhibiting the additional spread and treating patients affected by this pandemic. The neuronal cells infected with virus, immune systems (microphase, T cells, and monocytes) triggered, and inflammatory system activated leads to cytokine storm, oxidative stress, and associated neurological manifestations neuroinvasiveness of SARS-CoV-2 [11, 35] . In a recent review [51] , authors have categorized the reported neurological findings related to COVID-19 into three categories: a) Central (headache, dizziness, impaired consciousness, acute cerebrovascular disease, ataxia, seizures, and special senses) b) Peripheral (hypogeusia, hyposmia) c) Musculoskeletal (ischemic or hemorrhagic) Apart from the above, increasing evidence indicated that coronaviruses may invade the CNS, causing neurological disorders. cache = ./cache/cord-252389-xrdbmosj.txt txt = ./txt/cord-252389-xrdbmosj.txt === reduce.pl bib === id = cord-032751-pmclolvh author = Head, Katharine J. title = A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts date = 2020-09-23 pages = extension = .txt mime = text/plain words = 5086 sentences = 305 flesch = 48 summary = Research Question 2: What are the SARS-CoV-2 vaccine behavioral intentions of adults in the U.S. when a health care provider recommends the vaccine? Importantly, because vaccine intent and/or need may be different for people who were previously infected with SARS-CoV-2 and perceived threat variables (discussed below) are usually only measured for future threats, only participants who answered "no" to the question "do you believe that you've had COVID-19" are included in the current study (n = 3,159). Step 3 of the hierarchical regression model, with all variables included, less education was associated with lower intent to receive a SARS-CoV-2 vaccine. The health belief variables that were significant in the full regression model were all positively associated with intent to receive a SARS-CoV-2 vaccine. cache = ./cache/cord-032751-pmclolvh.txt txt = ./txt/cord-032751-pmclolvh.txt === reduce.pl bib === id = cord-019048-29wzpwvr author = Franks, Teri J. title = Coronavirus date = 2013-08-26 pages = extension = .txt mime = text/plain words = 2805 sentences = 135 flesch = 47 summary = From discovery to mid-September 2013, HCoV-EMC, renamed MERS-CoV, (de Groot 2013 ) caused 132 laboratory-confi rmed cases of severe acute pneumonia including 58 deaths. Certain structural proteins are common to all coronaviruses: the spike glycoprotein S, an envelope glycoprotein that mediates receptor-binding and membrane fusion; the envelope spanning glycoprotein M, which contributes to the thickness of the envelop; the envelope protein E, which has been identifi ed as a virulence factor SARS-CoV ; and the nucleocapsid protein N, with its function in genome encapsidation, RNA synthesis and translation, and as a type I interferon antagonist ( Fig. 13 .2 ). Initial signs and symptoms of SARS are nonspecifi c and common, which generates a wide differential diagnosis of respiratory pathogens including infl uenza virus, parainfl uenza Fig. 13.4 Acute-phase DAD in SARS patient. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection cache = ./cache/cord-019048-29wzpwvr.txt txt = ./txt/cord-019048-29wzpwvr.txt === reduce.pl bib === id = cord-254446-yxqbe1dj author = Ren, Yunzhao R. title = A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19 date = 2020-05-29 pages = extension = .txt mime = text/plain words = 6723 sentences = 426 flesch = 49 summary = The disease name -COVID-19‖ and the associated virus name -SARS-CoV-2‖ were coined by the World Health Organization (WHO) and the Coronavirus Study Group of the International Committee on Virus Taxonomy, respectively, on February 11 1, 2 . Interestingly, pharyngeal swab viral nucleic acid screening results of 2,510 patients between January 23 and February 25 from a hospital fever clinic in Hunan Province (a neighboring province of Hubei) demonstrated that the positive rate of SARS-CoV-2 (1.3%) was lower than that of Influenza A (2.3%) and Influenza B (3.3%) 42 . Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial cache = ./cache/cord-254446-yxqbe1dj.txt txt = ./txt/cord-254446-yxqbe1dj.txt === reduce.pl bib === id = cord-033551-eojpkxz9 author = Shekh, Shamasoddin title = In silico allicin induced S-thioallylation of SARS-CoV-2 main protease date = 2020-09-16 pages = extension = .txt mime = text/plain words = 3910 sentences = 248 flesch = 54 summary = In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 M(pro) using PX-12 as a benchmark reference compound. Figure 1a shows the structure of SARS-CoV-2 M pro with free cysteine thiols and active site dyad residues. Figure 2b shows the formation of cysteine allyl disulfide at the Cys-145 residue of SARS-CoV-2 M pro after covalent docking with allicin. Figure 4b and c show the formation of cysteine allyl disulfide at Cys-85 and Cys-156 residue of SARS-CoV-2 M pro after covalent docking with allyl sulfenic acid. Table-S2 provides a summary of covalent docking of allicin/PX-12/allyl sulfenic acid at cysteine thiols of four different co-crystal structures of SARS-CoV-2 M pro . Figure 5b shows the sulfur mediated hydrogen bonding by the sulfur of allyl disulfide formed after covalent docking of allicin at the active site of SARS-CoV-2 M pro . cache = ./cache/cord-033551-eojpkxz9.txt txt = ./txt/cord-033551-eojpkxz9.txt === reduce.pl bib === id = cord-032222-i6gfp4me author = Xue, Ling title = A quick look at the latest developments in the COVID-19 pandemic date = 2020-09-10 pages = extension = .txt mime = text/plain words = 2867 sentences = 206 flesch = 49 summary = Later, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses formally named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a novel coronavirus, and an effective vaccine has yet to be developed. 51 A recombinant adenovirus type 5 vector vaccine, developed by Chen Wei's team, showed good safety and immunogenicity in a phase I clinical trial, rapidly inducing both humoral and T-cell responses against SARS-CoV-2 in most participants. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia cache = ./cache/cord-032222-i6gfp4me.txt txt = ./txt/cord-032222-i6gfp4me.txt === reduce.pl bib === id = cord-150183-zzzyewjb author = Phillips, J. C. title = Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date = 2020-08-27 pages = extension = .txt mime = text/plain words = 2483 sentences = 154 flesch = 55 summary = These are (CoV-1 site numbering from Uniprot P59594): 546Gln to Leu; 556 and 561Ser to Ala; and 568Ser to Leu. The differences associated with each of these mutations are hydropathically large (~50-100 in the MZ scale [4] ; all 20 amino acids span a range from most hydrophilic to most hydrophobic of 170). The central hydrophilic level set, absent from CoV-1 and present in CoV-2, is our main result ( There is an excellent review of the principles of self-organized criticality in living matter [3] . Some readers may be interested in the connections between hydropathic scaling theory of proteins and the more general synchronization of complex networks. Now that we are in the genomic age, with a very large sequence data base available for many proteins and many species, the discovery of these 20 fractals [5, 13] opens a new biophysics field of accurate thermodynamic analysis of small but medically important evolutionary differences. cache = ./cache/cord-150183-zzzyewjb.txt txt = ./txt/cord-150183-zzzyewjb.txt === reduce.pl bib === id = cord-031289-uxoz0xhk author = Coccolini, Federico title = SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients date = 2020-05-18 pages = extension = .txt mime = text/plain words = 1326 sentences = 98 flesch = 51 summary = title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients The present article represents the very first positive result describing the presence of the virus in peritoneal fluid during an emergency surgical procedure in a COVID-19 sick patient. Interestingly, the nasal swab contained less SARS-CoV-2 RNA virus compared to the viral fluid that scored positive in 2 targets out of 3. This indicates that the viral load in the peritoneal fluid was higher compared to the upper respiratory material and suggests that the surgical operation was indeed a procedure at risk of infection. As no information exist about the virus passage to peritoneal cavity and fluids, present data may suggest that potentially all people even those with mild to moderate respiratory symptoms by SARS-CoV-2 could present viral load in peritoneal fluid, thus increasing the exposure and contagion risks for the entire surgical staff.Peritoneal fluid contamination with blood of feces may interfere with the virus detection. cache = ./cache/cord-031289-uxoz0xhk.txt txt = ./txt/cord-031289-uxoz0xhk.txt === reduce.pl bib === id = cord-256146-d599uera author = Kuiken, Thijs title = Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome date = 2003-07-26 pages = extension = .txt mime = text/plain words = 5686 sentences = 281 flesch = 49 summary = METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, human metapneumovirus, and other respiratory pathogens. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. . Serial dilutions of the SARS-CoV virus stock and SARS-CoV-infected Vero cells from patient 5688 were made and tested with the NP and polymerase-specific RT-PCRs. Samples from the respiratory tract (nasal swabs, pharyngeal swabs, postmortem trachea, and lung samples) were also monitored for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E), and human metapneumovirus with use of essentially the same RT-PCR methods but with specific primers. Virological examinations of nasal and pharyngeal swabs, and tracheal and lung samples from all four macaques by RT-PCR for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E) and human metapneumovirus were negative. cache = ./cache/cord-256146-d599uera.txt txt = ./txt/cord-256146-d599uera.txt === reduce.pl bib === id = cord-253457-gawn4s9g author = Yau, Kevin title = COVID-19 Outbreak in an Urban Hemodialysis Unit date = 2020-07-15 pages = extension = .txt mime = text/plain words = 2215 sentences = 145 flesch = 47 summary = Patients with SARS-CoV-2 infection including asymptomatic individuals were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR testing. Nasopharyngeal swabs were performed by physicians, nurse practitioners, and staff from the hospital's COVID-19 Assessment Centre under droplet and contact precautions in the hemodialysis unit with curtains drawn around the dialysis station at which the patient was being swabbed. At the time of testing, six (55%) patients and six (55%) staff positive for SARS-CoV-2 were asymptomatic. Patients with confirmed SARS-CoV-2 infection including asymptomatic individuals were dialyzed in a dedicated room separate from the main hemodialysis unit for the duration of their infection and maintained on droplet and contact precautions. Five hemodialysis staff were allowed to return to work following symptom resolution and documentation of two negative SARS-CoV-2 nasopharyngeal swabs performed 14 days from symptom onset. Infection control authorities concluded that SARS-CoV-2 transmission during an outbreak at the St. Michael's Hospital hemodialysis unit was likely to have originated from two index cases. cache = ./cache/cord-253457-gawn4s9g.txt txt = ./txt/cord-253457-gawn4s9g.txt === reduce.pl bib === id = cord-254636-3lr008th author = Shishir, Tushar Ahmed title = In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date = 2020-08-16 pages = extension = .txt mime = text/plain words = 2974 sentences = 171 flesch = 54 summary = We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. We conducted comparative analysis of publicly available genome sequences of SARS-CoV-2 from 27 countries to predict the origin of viruses in Bangladesh by studying a time-4 resolved phylogenetic relationship. Later, we analyzed the variants present in different isolates of Bangladesh to understand the pattern of mutations in relation to the ancestral Wuhan strain, find unique mutations, and possible effect of these mutations on the stability of encoded proteins, and selection pressure on genes. cache = ./cache/cord-254636-3lr008th.txt txt = ./txt/cord-254636-3lr008th.txt === reduce.pl bib === id = cord-253844-y6xdcf20 author = Yesudhas, Dhanusha title = COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date = 2020-09-04 pages = extension = .txt mime = text/plain words = 7165 sentences = 422 flesch = 51 summary = In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. The sequence similarity between SARS-CoV-2 and SARS-CoV spike proteins explains the possibility of binding to the same receptor angiotensin converting enzyme 2 (ACE2) in the host cell [14] . In this review, we discuss the history of coronaviruses in both humans and animals, their transmissions, mechanism of host cell entry and the structural studies, explaining active and inactive receptor binding of spike protein and the key residues playing an important role in the receptor binding. During viral infection, spike protein (~ 1300 amino acid residues) is cleaved by host proteases into receptor binding subunit S1 and membrane fusion subunit S2. cache = ./cache/cord-253844-y6xdcf20.txt txt = ./txt/cord-253844-y6xdcf20.txt === reduce.pl bib === id = cord-252600-bvh1o64r author = Galasiti Kankanamalage, Anushka C. title = Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element date = 2018-04-25 pages = extension = .txt mime = text/plain words = 4752 sentences = 254 flesch = 54 summary = We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ). cache = ./cache/cord-252600-bvh1o64r.txt txt = ./txt/cord-252600-bvh1o64r.txt === reduce.pl bib === id = cord-104500-m0kfom0x author = Kyriakopoulos, Anthony M. title = The Potential Role of Super Spread Events in SARS-COV-2 Pandemic; a Narrative Review date = 2020-09-21 pages = extension = .txt mime = text/plain words = 6842 sentences = 357 flesch = 40 summary = A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic" and were published before 20(th) of August 2020. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. Following this initial selection stage, further screening was performed by all reviewers, using the previously described search items to identify parameters determining the global impact of COVID-19 due to SSEs. Identified parameters included the global impact of immunity and vaccination, the holy cup and religion transmission, and the austerity caused by COVID-19 and other coronavirus epidemics due to restrictions applied. cache = ./cache/cord-104500-m0kfom0x.txt txt = ./txt/cord-104500-m0kfom0x.txt === reduce.pl bib === id = cord-252767-as841xo0 author = Fischer, Bastian title = SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 date = 2020-07-16 pages = extension = .txt mime = text/plain words = 2028 sentences = 110 flesch = 49 summary = We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. To determine an approximation of the actual rate of people who have recovered from COVID-19, representative of the German population, we determined the anti-SARS-CoV-2 IgG seroprevalence of regular blood donors resident in three different German federal states between March and June 2020. The Figure shows the anti-SARS-CoV-2 IgG distribution in blood donors with equivocal (ratio: ≥ 0.8 to < 1.1) and clearly seropositive (ratio: ≥ 1.1) test results. Distribution of anti-SARS-CoV-2 IgG ratios of blood donors with seropositive and equivocal test results, Germany, March-June 2020, (n = 3,186) cache = ./cache/cord-252767-as841xo0.txt txt = ./txt/cord-252767-as841xo0.txt === reduce.pl bib === id = cord-256508-ce59ovan author = Asselah, Tarik title = COVID-19: discovery, diagnostics and drug development date = 2020-10-08 pages = extension = .txt mime = text/plain words = 9214 sentences = 556 flesch = 46 summary = To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The current diagnostic strategy to identify patients with COVID-19 is to test samples taken from the respiratory tract to assess for the presence of SARS-CoV-2 specific nucleic acid targets [47] . The neutralization assay is a laboratory-based test that uses live virus and cell culture methods to determine if patient antibodies can prevent viral infection in vitro [72] . A randomized, controlled, openlabel trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection and severe respiratory illness COVID-19 was performed [126] . Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals cache = ./cache/cord-256508-ce59ovan.txt txt = ./txt/cord-256508-ce59ovan.txt === reduce.pl bib === id = cord-193133-puqcbf8t author = Piplani, Sakshi title = In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date = 2020-05-13 pages = extension = .txt mime = text/plain words = 3815 sentences = 215 flesch = 51 summary = The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species. 31, 32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The molecular dynamics simulation of complexes of SARS-CoV-2 spike protein and ACE2 receptors of various species were performed for 100ns. cache = ./cache/cord-193133-puqcbf8t.txt txt = ./txt/cord-193133-puqcbf8t.txt === reduce.pl bib === id = cord-256888-tdx12ccj author = Bradley, Benjamin T title = Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series date = 2020-07-16 pages = extension = .txt mime = text/plain words = 5006 sentences = 300 flesch = 45 summary = To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. 8 Post-mortem studies have shown pulmonary, renal, and small vessel injury, with particles resembling virus observed in the kidney by electron microscopy. By electron microscopy, aggregates of uniform, round enveloped particles ranging in size from around 70 nm to 100 nm with peripheral spike-like projections consistent with the morphology described for SARS-CoV-2 were observed in the lung, trachea, kidney, and large intestine of patient 8 and patient 13. [9] [10] [11] [12] We present a case series of autopsy findings in 14 patients who died after SARS-CoV-2 infection. The major histopathological observation in our series of patients who died with COVID-19 was diffuse alveolar damage-type lung injury in the acute or organising phases (12 [86%] of 14 patients). cache = ./cache/cord-256888-tdx12ccj.txt txt = ./txt/cord-256888-tdx12ccj.txt === reduce.pl bib === id = cord-033780-184e64tr author = Smith, Rasheid title = Implications of current and future approaches to coronavirus disease 2019 testing date = 2020-10-13 pages = extension = .txt mime = text/plain words = 3266 sentences = 154 flesch = 44 summary = The current reality is that SARS-CoV-2 is a highly transmissible airborne disease with a broad presentation of symptoms and leaves lasting damage in severe cases, and for which there is a scarcity of effective medications to treat it. Using the cycle threshold value in this manner only informs as to the presence of the virus and may not reveal disease progression, severity and viral load in the sample; and as such the results are largely qualitative despite the inherent quantitative nature of real-time RT-PCR [27] . Nevertheless, initial studies have demonstrated that chest CT imaging is more accurate than RT-PCR at detecting SARS-CoV-2 patients [32] with 97.2% versus 83% in the early stages of infection [33] . Immunoassays (antibody serum tests), such as enzyme-linked immunosorbent assays (ELISAs), are used to detect the presence of serum antibodies (either IgA, IgG or IgM) to viral proteins and can indicate when a person has developed an immune response to SARS-CoV-2. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor cache = ./cache/cord-033780-184e64tr.txt txt = ./txt/cord-033780-184e64tr.txt === reduce.pl bib === id = cord-252232-vgq6gjpx author = Hou, Yuxuan title = Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry date = 2010-06-22 pages = extension = .txt mime = text/plain words = 3208 sentences = 159 flesch = 57 summary = Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. However, although the genetically related SARS-like coronavirus (SL-CoV) has been identified in horseshoe bats of the genus Rhinolophus [5, 8, 12, 18] , its spike protein was not able to use the human ACE2 (hACE2) protein as a receptor [13] . To this end, we have extended our studies to include ACE2 molecules from different bat species and examined their interaction with the human SARS-CoV spike protein. Our results show that there is great genetic diversity among bat ACE2 molecules, especially at the key residues known to be important for interacting with the viral spike protein, and that ACE2s of Myotis daubentoni and Rhinolophus sinicus from Hubei province can support viral entry. cache = ./cache/cord-252232-vgq6gjpx.txt txt = ./txt/cord-252232-vgq6gjpx.txt === reduce.pl bib === id = cord-029547-9ei1ram3 author = Li, Jingwei title = The epidemiology and therapeutic options for the COVID-19 date = 2020-05-28 pages = extension = .txt mime = text/plain words = 7841 sentences = 499 flesch = 48 summary = According to the Diagnosis and Treatment Program of Novel Coronavirus Pneumonia, only a suspected case has one of the pieces of evidence of etiology or serology, such as positive nucleic acid, confirmation of gene sequencing, and virus specific antibody, to be confirmed to be COVID-19 patient, 55 and the suspected cases were identified by a comprehensive analysis of epidemiological history and clinical manifestations. 64 There have been tens of clinical trials to confirm the safety and efficiency of chloroquine in treating COVID-19 patients, and its mechanism can be described as interfering with the glycosylation of ACE2 or alkalizing the phagolysosome to inhibit viral replication, 65, 66 which prevents the SARS-Cov-2 entering the host cells. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial cache = ./cache/cord-029547-9ei1ram3.txt txt = ./txt/cord-029547-9ei1ram3.txt === reduce.pl bib === id = cord-253905-zknmfgsh author = Li, Xingguang title = Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 date = 2020-03-11 pages = extension = .txt mime = text/plain words = 3846 sentences = 194 flesch = 49 summary = To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. Homology plot analysis of "dataset_6" also revealed that BetaCoV/bat/Yunnan/ RaTG13/2013 was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378), consistent with phylogenetic analysis ( Figure S5 ). 46, 47 Bayesian analyses with the tip-dating method using a strict clock as well as constant size coalescent tree prior indicated that SARS-CoV-2 is evolving at a rate of 1.24 × 10 −3 substitutions per site per year (Table 1 ), in accordance with our prior research 46, 47 and similar to that found for other human F I G U R E 4 Estimated maximum-clade-credibility tree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using tip-dating method. cache = ./cache/cord-253905-zknmfgsh.txt txt = ./txt/cord-253905-zknmfgsh.txt === reduce.pl bib === id = cord-256020-wrui3i2l author = Fadaka, Adewale Oluwaseun title = Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date = 2020-08-26 pages = extension = .txt mime = text/plain words = 7097 sentences = 465 flesch = 49 summary = The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations cache = ./cache/cord-256020-wrui3i2l.txt txt = ./txt/cord-256020-wrui3i2l.txt === reduce.pl bib === id = cord-252049-rgdynmla author = Tomar, Sakshi title = Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS date = 2015-06-08 pages = extension = .txt mime = text/plain words = 11805 sentences = 601 flesch = 56 summary = All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Therefore, we determined the dependence of the enzymatic activity of MERS-CoV 3CL pro on the total enzyme concentration and compared it with other 3CL pro enzymes from HKU4, HKU5, and SARS coronaviruses (Fig. 2) . The kinetic data for all four 3CL pro enzymes, MERS-CoV, HKU4-CoV, HKU5-CoV, and SARS-CoV, fit well to this model, and the resulting values for the monomer-dimer equilibrium dissociation constant, K d , and apparent turnover number, k cat , for each enzyme are provided in Table 2 . Compound 11 also forms two direct and one water-mediated hydrogen bond interactions with amino acids in the MERS-CoV 3CL pro active site (Fig. 6E) . cache = ./cache/cord-252049-rgdynmla.txt txt = ./txt/cord-252049-rgdynmla.txt === reduce.pl bib === id = cord-024317-w1ep0wq8 author = Ku, Zhiqiang title = Antibody therapies for the treatment of COVID-19 date = 2020-04-30 pages = extension = .txt mime = text/plain words = 2215 sentences = 152 flesch = 47 summary = Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. The spike protein of SARS-CoV-2 plays an essential role in virus entry into host cells and is a primary target of neutralizing antibodies 5, 9 (Figures 1C,D) . Two MERS-CoV neutralizing mAbs, G2 and 7D10, target the S1-NTD region and function by blocking spike protein interaction with the host receptor DPP4 47, 48 . In the monkey study, researchers found that rhesus macaques infected with SARS-CoV-2 through the intratracheal route had mild illness, and their lungs showed signs of pneumonia similar to those in humans with COVID-19 58 . cache = ./cache/cord-024317-w1ep0wq8.txt txt = ./txt/cord-024317-w1ep0wq8.txt === reduce.pl bib === id = cord-030934-t7akdu6x author = Bahrami, Afsane title = Genetic and pathogenic characterization of SARS-CoV-2: a review date = 2020-08-26 pages = extension = .txt mime = text/plain words = 6472 sentences = 356 flesch = 45 summary = The first case of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019. Bioinformatics analysis of the viral genome from one COVID-19 patient shared 89 and 82% sequence similarity with bat SARS-like-CoVZXC21 and human SARS-CoV, respectively [41] . In a recent report it was shown that SARS-CoV-2's S-protein entry into 293/human ACE2 receptor cells is primarily mediated via endocytosis, and that PIKfyve, a TPC2 and cathepsin L are crucial for virus entry. Findings of an open-label nonrandomized clinical trial among 22 infected patients indicated that hydroxychloroquine treatment significantly reduced viral load in COVID-19 cases and its effectiveness is promoted by azithromycin [99] . The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response cache = ./cache/cord-030934-t7akdu6x.txt txt = ./txt/cord-030934-t7akdu6x.txt === reduce.pl bib === id = cord-258268-7ypq0t3d author = Zanin, Luca title = SARS-CoV-2 can induce brain and spine demyelinating lesions date = 2020-05-04 pages = extension = .txt mime = text/plain words = 1481 sentences = 113 flesch = 47 summary = On January 24, 2020, a new virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been identified, quickly gaining worldwide attention [21] . Similarly to other Coronavirus, SARS-CoV-2 can attack the olfactory bulb and then affect the central nervous system (CNS) through the olfactory tract in the early stages of infection [5] . Neurological impairment and demyelinating reaction appear as complications in case of severe Coronavirus Disease 2019 (COVID-19) [10] . Our patient showed symptoms consistent with a neurological involvement consequent to SARS-CoV-2 infection. In SARS-CoV-2 infection, neurological impairment was observed only in case of severe COVID-19 [10] . SARS-CoV-2 was not detected in the CSF probably because the neurological damage was sustained by a delayed immune response that occurred after the viremia. Sudden neurological impairment with seizures in COVID-19 patients may be sustained by CNS involvement and demyelinating lesions. Neurologic features in severe SARS-CoV-2 infection cache = ./cache/cord-258268-7ypq0t3d.txt txt = ./txt/cord-258268-7ypq0t3d.txt === reduce.pl bib === id = cord-254395-tu4aqczj author = Froggatt, Heather M. title = Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CL(pro) Reporter Assay date = 2020-10-27 pages = extension = .txt mime = text/plain words = 4200 sentences = 254 flesch = 50 summary = This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. With the aim of generating a protease reporter compatible with SARS-CoV-2 and other present and future coronaviruses to support viral inhibitor screening, we selected CoV 3CL pro as our protease target. (C) Quantification of fluorescence from 293T cells 48 h after transfection with each FlipGFP reporter and either the SARS-CoV-2 3CL pro or an influenza virus protein (A/PR8/1834 NP). To observe whether these FlipGFP constructs background fluoresced without CoV 3CL pro activity, we transfected cells with each reporter or a superfolder GFP (sfGFP) expression plasmid. Development of a FlipGFP CoV 3CL pro reporter-based assay for protease inhibitor screening in human cells. cache = ./cache/cord-254395-tu4aqczj.txt txt = ./txt/cord-254395-tu4aqczj.txt === reduce.pl bib === id = cord-256217-fnjer0e0 author = Neri, Piergiorgio title = COVID-19 and the eye immunity: lesson learned from the past and possible new therapeutic insights date = 2020-04-20 pages = extension = .txt mime = text/plain words = 1928 sentences = 88 flesch = 43 summary = Corona virus represents nowadays the hot topic in the scientific world due to the outbreak of a novel serotype formerly named coronavirus disease (COVID)-19 and now identified as severe acute respiratory syndrome (SARS)-COV-2 [1] . Although ECOR was used to study retinal degeneration specifically, it might represent a possible experimental model for interesting speculations on how to approach severe SARS-COV-2 pulmonary complications. Looking at the ECOR model, it gives the impression that coronavirus creates two different phases: the first is represented by the primary infection which induces the triggering of the immune system, while the second phase is likely to be an autoimmune disease where the role of the severe postviral inflammation represents a severe occurrence worth of prompt intervention. Albeit it is true that anti-IL-6 receptor monoclonal antibody has given promising results for the control of severe SARS-COV-2 pneumonia, it is interesting to notice that retinal degeneration in ECOR is associated with an evident increase in TNF-alpha, as well as soluble TNFR2, inducing an anomaly of TNF-alpha signaling [12] . cache = ./cache/cord-256217-fnjer0e0.txt txt = ./txt/cord-256217-fnjer0e0.txt === reduce.pl bib === id = cord-256737-ptjng78b author = McBride, Corrin E. title = Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein date = 2010-09-01 pages = extension = .txt mime = text/plain words = 8233 sentences = 414 flesch = 58 summary = The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Importantly, we show that SARS-CoV S palmitoylation is not necessary for efficient interaction with SARS-CoV M, which differs from published experiments for MHV (Thorp et al., 2006) and suggests a significant difference between the two viruses that may have important implications for virus assembly and infectivity. To determine if SARS-CoV S becomes palmitoylated in a pre-medial Golgi compartment, HEK293T cells exogenously expressing SARS-CoV S were labeled for 30 min with 35 S-methionine/ cysteine to measure total protein expression or 3 H-palmitic acid to measure palmitoylated protein. Although both SARS-CoV S and S PN were present at the cell surface, it is possible that there could be a difference in the amount of protein at the plasma membrane at steady state if palmitoylation affects a post-Golgi trafficking step. cache = ./cache/cord-256737-ptjng78b.txt txt = ./txt/cord-256737-ptjng78b.txt === reduce.pl bib === id = cord-214854-ck61ja2t author = Zhong, Jing title = Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles date = 2020-10-08 pages = extension = .txt mime = text/plain words = 2059 sentences = 120 flesch = 47 summary = Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and sensitive detection of specific biomolecules, e.g. protein, DNA/RNA and virus. demonstrated the feasibility of wash-free, sensitive and specific assays for the detection of different viruses, e.g. orchid and influenza viruses, with antibody-functionalized MNPs by measuring the reduction in the ac susceptibility in mixed-frequency ac magnetic fields [23] [24] [25] . All these approaches have demonstrated that MNP-based homogeneous biosensing is a wash-free and mix-and-measure approach for rapid and sensitive detection of specific biomolecules. cache = ./cache/cord-214854-ck61ja2t.txt txt = ./txt/cord-214854-ck61ja2t.txt === reduce.pl bib === === reduce.pl bib === id = cord-255997-oer5lxxr author = Onodi, Fanny title = SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date = 2020-07-10 pages = extension = .txt mime = text/plain words = 4209 sentences = 254 flesch = 53 summary = Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . cache = ./cache/cord-255997-oer5lxxr.txt txt = ./txt/cord-255997-oer5lxxr.txt === reduce.pl bib === === reduce.pl bib === id = cord-258881-74aijckl author = Wang, Maomao title = Case Report: One Case of Coronavirus Desease 2019(COVID-19) in Patient Co-nfected by HIV With a Low CD4+ T Cell Count date = 2020-04-23 pages = extension = .txt mime = text/plain words = 670 sentences = 45 flesch = 64 summary = Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China has become an emergency of international concern When thousands of peolple were infected around the world.We report a case infected by SARS-Cov-2 and HIV simultaneously,which showed a longer course of disease and slower generation of specific antibody. Here we report a patient infected by SARS-Cov-2 , who had a relatively long course of disease with unstable state. Then eight markers of infectious diseases was checked and the result showed that abtibodies to HIV and syphilis were positive .Then the patient was transferred to specialty hospital for further treatment on March 8. People are generally susceptible to SARS-Cov-2 infection, especially the elderly patients and those with underlying diseases [2] . The author suggested that SARS-Cov-2 might damage lymphocytes, especially T lymphocytes, and the immune system was impaired during the period of disease [2] . In conclusion, we report the clinical features of a patient infected by SARS-Cov-2 and HIV. cache = ./cache/cord-258881-74aijckl.txt txt = ./txt/cord-258881-74aijckl.txt === reduce.pl bib === id = cord-255815-5d9bqji0 author = Malik, Ajamaluddin title = MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization date = 2017-05-30 pages = extension = .txt mime = text/plain words = 3925 sentences = 243 flesch = 59 summary = An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. In a similar experiment, MERS-CoV PL pro was gradually heated from 20 to 80°C at a rate of 1°C/min during which tryptophan fluorescence was measured by exciting at 295 nm and collecting at 330 and 350 nm to obtain the temperature melting curve. Commonly, protein unfolding fluorescence spectra are characterized by a long wavelength shift ''red-shift.'' But some proteins, Fig. 2 a Sequence of C-terminal His-tagged MERS-CoV PL pro showing ten Tyr and five Trp residues, which are highlighted in green and blue, respectively. Our result showed that the band intensity of the supernatant samples incubated from 20 to 70°C was apparently unchanged (Fig. 5) , indicating Fig. 3 Thermally induced structural changes in MERS-CoV PL pro as monitored by the intrinsic tryptophan fluorescence spectroscopy. cache = ./cache/cord-255815-5d9bqji0.txt txt = ./txt/cord-255815-5d9bqji0.txt === reduce.pl bib === id = cord-255883-mz6nyisw author = Asif, Muhammad title = COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties date = 2020-08-14 pages = extension = .txt mime = text/plain words = 5273 sentences = 283 flesch = 44 summary = Essential oils (EOs) have long been known to have anti-inflammatory, immunomodulatory, bronchodilatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2 virus. An in vitro study conducted by Hoffmann and colleagues revealed that SARC-CoV-2 depends on cellular serine protease (TMPRSS2) for S proteins priming which are known to interact with human ACE2 receptors in the lungs and facilitate entry into the cells. The authors opted the following keywords to find relevant studies: "essential oils", "antiviral", "COVID-19", "SARC-CoV-2", "bronchodilation", "immunomodulatory'', "anti-inflammatory'', "corona virus''. Thus, on the basis of these docking and in vitro studies, it is proposed that garlic essential oils and their isolated constituents, especially DAS, have potential to prevent the entry of virus into host cells as well as to activate molecular antioxidant pathways that decrease the secretions of culprit pro-inflammatory cytokines. Essential oils have long been known to have anti-inflammatory, antioxidant, immunomodulatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2. cache = ./cache/cord-255883-mz6nyisw.txt txt = ./txt/cord-255883-mz6nyisw.txt === reduce.pl bib === id = cord-255552-k1retwa4 author = Gassen, Nils C. title = Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date = 2020-04-15 pages = extension = .txt mime = text/plain words = 1208 sentences = 73 flesch = 39 summary = Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) . cache = ./cache/cord-255552-k1retwa4.txt txt = ./txt/cord-255552-k1retwa4.txt === reduce.pl bib === id = cord-034354-4xu97je3 author = Wang, Hongye title = SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution date = 2020-10-21 pages = extension = .txt mime = text/plain words = 3678 sentences = 245 flesch = 53 summary = The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. Using the SARS-CoV-2 proteome microarray, we screened IgM and IgG antibodies in the serum of 10 COVID-19 patients who were in the early stage of infection (days of symptoms onset, 3.0 ± 5.92) (Supporting Information, Table S2 ) to construct a landscape of humoral responses to the SARS-CoV-2 proteome (Figure 2 ). Sixty-one (61) IgG and IgM antibody epitopes were identified in seven SARS-CoV-2 proteins (M, N, S, Orf1ab, Orf3a, Orf7a, and Orf8) with a Z-score higher than 3 in at least one COVID-19 patient (Table 1) . Furthermore, we constructed the first landscape of B-cell epitopes of serum IgM and IgG antibodies, representing the comprehensive antibody response of COVID-19 patients to SARS-CoV-2 infection (Figures 2−4) . cache = ./cache/cord-034354-4xu97je3.txt txt = ./txt/cord-034354-4xu97je3.txt === reduce.pl bib === id = cord-259603-bh198xgl author = Snijder, E.J. title = The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date = 2016-09-14 pages = extension = .txt mime = text/plain words = 24187 sentences = 1090 flesch = 50 summary = Reverse-genetics studies targeting specific residues in SARS-CoV nsp7 confirmed the protein's importance for virus replication (Subissi et al., 2014b) , although the impact of single point mutations was smaller than anticipated on the basis of the biochemical characterization of the RNA-binding properties of nsp7-containing protein complexes in vitro (see later). The large number of viral subunits in these complexes (Subissi et al., 2014a) , the likely requirement for host factors (van Hemert et al., 2008) , and the concept of RNA synthesis occurring in a dedicated microenvironment in the infected cell (Knoops et al., 2008; V'Kovski et al., 2015) complicate the straightforward characterization of the CoV RdRp. To reconstitute the enzyme's activities in vitro, purified recombinant nsp12 is a key reagent but, for many years, such studies were hampered by poor nsp12 expression in Escherichia coli. cache = ./cache/cord-259603-bh198xgl.txt txt = ./txt/cord-259603-bh198xgl.txt === reduce.pl bib === id = cord-254968-czrgzyr3 author = Zhang, Qiang title = A serological survey of SARS-CoV-2 in cat in Wuhan date = 2020-09-17 pages = extension = .txt mime = text/plain words = 3148 sentences = 180 flesch = 56 summary = Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19. Here, we investigated the serological prevalence of SARS-CoV-2 in cats by an indirect ELISA and virus neutralization tests (VNT), and monitored the serum antibody dynamics of cats infected SARS-CoV-2, providing a basis for further understanding the infection of SARS-CoV-2 in cats. In this study, we detected the presence of SARS-CoV-2 antibodies in cats in Wuhan during the COVID-19 outbreak with ELISA, VNT and western blot. Virus neutralization test and Western blot assay of cat serum samples for SARS-CoV-2 (A) Cat#14, Cat#15 and Cat#4 sera were 3-fold serially diluted and mixed with SARS-CoV-2; after incubated at 37°C for 1 h, the mixture was used to infect Vero E6 cells, and replaced with semi-solid media 1 h later. cache = ./cache/cord-254968-czrgzyr3.txt txt = ./txt/cord-254968-czrgzyr3.txt === reduce.pl bib === id = cord-254469-7q6xi2xx author = Wang, Fuzhou title = An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development date = 2020-05-05 pages = extension = .txt mime = text/plain words = 4737 sentences = 245 flesch = 48 summary = In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). However, on March 16 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US), conducted by Moderna and the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) [12, 13] . Although mRNA vaccines are commencing human clinical trials, due to the rapid global spread of this new viral pandemic, it may not be possible to develop a safe and effective vaccine for SARS-CoV-2 in time to prevent the increasing number of deaths due to this novel RNA virus. cache = ./cache/cord-254469-7q6xi2xx.txt txt = ./txt/cord-254469-7q6xi2xx.txt === reduce.pl bib === id = cord-257958-yehnlabq author = Barh, Debmalya title = Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19 date = 2020-10-10 pages = extension = .txt mime = text/plain words = 5431 sentences = 364 flesch = 43 summary = In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. In this paper, we have used an integrative omics approach considering the SARS-CoV-2 infected host interactome, proteome, transcriptome, and bibliome datasets and analysed the COVID-19 associated host genetic information to identify common host pathways that are deregulated during SARS-CoV-2 infection and potential drugs targeting those pathways. In our analysis, we observed SARS-CoV-2 infection shares other viral pathways such as To identify pathway specific drugs, we used the genes involved in the five most important common pathways (viral processes including all the individual virus pathways, mRNA splicing, ubiquitin mediated proteolysis, cytokine signaling in immune system, and protein processing in endoplasmic reticulum). cache = ./cache/cord-257958-yehnlabq.txt txt = ./txt/cord-257958-yehnlabq.txt === reduce.pl bib === id = cord-258914-g6pv8zz9 author = Proud, Pamela C. title = Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date = 2020-09-25 pages = extension = .txt mime = text/plain words = 1191 sentences = 90 flesch = 51 summary = title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. The TLRs are key microbe-recognition receptors with a crucial role in 97 activation of host defence and protection from infections and therefore attractive drug 98 targets against infectious diseases [12] [13] [14] To determine whether TLR2/6 agonists are also active against SARS-CoV-2, we used In life samples were taken at days 1, 3, 5, 7, 10 and 12, with scheduled culls at days 137 3 (n=6) and end of study days 12-14 (n=18) (Fig 1A) . cache = ./cache/cord-258914-g6pv8zz9.txt txt = ./txt/cord-258914-g6pv8zz9.txt === reduce.pl bib === id = cord-258312-3v5t4k8d author = Majachani, Nicole title = A Case of a Newborn Baby Girl Infected with SARS-CoV-2 Due to Transplacental Viral Transmission date = 2020-10-25 pages = extension = .txt mime = text/plain words = 1962 sentences = 131 flesch = 51 summary = Patient: Female, 31-year-old Final Diagnosis: COVID-19 • SARS-CoV-2 Symptoms: Asymptomatic Medication:— Clinical Procedure: — Specialty: Pediatrics and Neonatology OBJECTIVE: Unusual clinical course BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus and is responsible for the current pandemic. CASE REPORT: 31-year-old Hispanic woman in the final week of pregnancy developed mild respiratory symptoms of COVID-19 pneumonia and tested positive for SARS-CoV-2 infection. In response to the potential risks to both the mother and fetus, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control have developed guidelines which provide a framework for detecting infections early and preventing potential transmission of SARS-CoV-2. Although similar viruses like severe acute respiratory syndrome coronavirus 1 have not demonstrated the ability to cause fetal infection, SARS-CoV-2 is able to bind ACE2 with much higher affinity [11] , thus increasing the probability of transplacental transmission. cache = ./cache/cord-258312-3v5t4k8d.txt txt = ./txt/cord-258312-3v5t4k8d.txt === reduce.pl bib === id = cord-258595-bk35vxlr author = Westhaus, Sandra title = Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks date = 2020-08-18 pages = extension = .txt mime = text/plain words = 4965 sentences = 305 flesch = 57 summary = Inoculation of differentiated Caco-2 cells for ten days with purified and concentrated wastewater (P2, P5, P11, and P12) did not result in the production of infectious SARS-CoV-2 particles (data not shown), which suggests that treated sewage appears to be non-infectious even though viral RNA fragments can be detected. Inter-comparing these nine catchment areas, we plotted the estimated cumulative and the acute prevalence against the measured SARS-CoV-2 load (Figure 8 ), the latter calculated from RT-qPCR measured M-gene copy concentration ( Figure 4 ) and the actual wastewater flow Q actual on the day of sampling (Table 2) . In contrast, plotting the incidence against SARS-CoV-2 concentration did not yield a conclusive correlation (not shown), likely because the precision of the qPCR employed was not sufficient to discriminate relatively minor differences in the incidence prevailing in the studied catchment areas at the time of sampling, ranging from 30 to 174 cases per 100,000 residents (less than an order of magnitude, Figure 8C and D). cache = ./cache/cord-258595-bk35vxlr.txt txt = ./txt/cord-258595-bk35vxlr.txt === reduce.pl bib === id = cord-262328-q7mt0xve author = Wajnberg, Ania title = Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study date = 2020-09-25 pages = extension = .txt mime = text/plain words = 4419 sentences = 216 flesch = 54 summary = In this observational study, we ran an outreach programme in the New York City (NY, USA) area, including parts of Connecticut and New Jersey, to identify people who had recovered from SARS-CoV-2 infection for nasopharyngeal PCR (cobas 6800; Roche Diagnostics, Indianapolis, IN, USA) and serum IgG titre measurement (ELISA; Icahn School of Medicine at Mount Sinai, New York, NY, USA). We did not find reports of ELISA antibody assays as large as this one from areas with major COVID-19 hotspots, and found mixed and growing reports of IgG response to and PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over time. In the 584 participants for whom both nasopharyngeal PCR testing and serum antibody testing was available, SARS-CoV-2 RNA was detected in 249 (43%) at a median of 20 days (IQR 18-23) from symptom onset and 12 days (9-14) from symptom resolution. cache = ./cache/cord-262328-q7mt0xve.txt txt = ./txt/cord-262328-q7mt0xve.txt === reduce.pl bib === id = cord-260729-b12v3c8c author = de Lang, Anna title = Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date = 2007-08-10 pages = extension = .txt mime = text/plain words = 6800 sentences = 335 flesch = 51 summary = As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. In order to elucidate early host responses during the acute phase of SARS-CoV infection, we infected cynomolgus macaques with SARS-CoV and used macaque-specific microarrays and real-time (RT)-PCR techniques to study host gene expression profiles. In this study, we simultaneously examined virus replication and host-response gene expression profiles in macaque lungs during the acute phase of SARS to gain more insight into the early events that take place after SARS-CoV infection. In order to visualize the host response in the lungs of SARS-CoV-infected macaques, IFN-b production and translocation of phosphorylated STAT1 was studied using immunohistochemistry. The expression of IFN-b, which strongly correlated to the amount of virus present, continued throughout day 4 and was confirmed using immunohistochemistry; IFN-b-positive cells could be detected in the lungs of the SARS-CoV-infected macaques. cache = ./cache/cord-260729-b12v3c8c.txt txt = ./txt/cord-260729-b12v3c8c.txt === reduce.pl bib === id = cord-253665-1dn3ek34 author = Vishnubalaji, Radhakrishnan title = Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response date = 2020-07-07 pages = extension = .txt mime = text/plain words = 5427 sentences = 301 flesch = 42 summary = Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) on Phenomenal changes in ncRNA expression are also seen within host cells, which can play a major role in respiratory virus pathogenesis, with long non-coding RNAs (lncRNAs) exhibiting higher tissue specificity than coding genes [30] . Disease and function analysis on the differentially expressed genes revealed the most significant enrichment in pathways related to reactive oxygen species, induction of apoptosis and necrosis, as well as activation of neutrophils in SARS-CoV-2 infected NHBE cells (Figure 3a,b) . The top ten activated upstream regulator networks (CST5, IFNG, IFNL1, IFNA2, SPI1, RNY3, PRL, TGM2 , miR-122 and miR-122-5p) in lung tissue derived from COVID-19 patient based on transcriptome and IPA analyses, revealed the enrichment of functions related to immune system associated JAK-STAT cascade, type 1 interferon receptor binding, cytokine receptor binding, and MHC 1 biosynthesis (Figure 6a and Supplementary Table S10 ). cache = ./cache/cord-253665-1dn3ek34.txt txt = ./txt/cord-253665-1dn3ek34.txt === reduce.pl bib === id = cord-265322-3854ddb9 author = Vavougios, George D. title = A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date = 2020-04-23 pages = extension = .txt mime = text/plain words = 1252 sentences = 72 flesch = 41 summary = Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host's metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? cache = ./cache/cord-265322-3854ddb9.txt txt = ./txt/cord-265322-3854ddb9.txt === reduce.pl bib === id = cord-265128-i0d4lxko author = Gurung, Arun Bahadur title = Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach date = 2020-05-22 pages = extension = .txt mime = text/plain words = 2234 sentences = 168 flesch = 57 summary = Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Structure-based drug design primarily relies on molecular docking to identify lead molecules against the target proteins from chemical libraries [12, 13] . The natural products such as traditional medicines and plant-derived compounds (phytochemicals) are the rich sources of promising antiviral drugs [14] . The binding energies and inhibition constants of the phytochemicals with the SARS-CoV-2 M pro enzyme were compared with that of a set of twelve FDA approved antiviral drugs-a) Viral cache = ./cache/cord-265128-i0d4lxko.txt txt = ./txt/cord-265128-i0d4lxko.txt === reduce.pl bib === id = cord-261718-zqoggwnk author = Pietschmann, Jan title = Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date = 2020-06-03 pages = extension = .txt mime = text/plain words = 1188 sentences = 76 flesch = 45 summary = Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. After addition of 176 biotinylated GaR and subsequent labelling with streptavidin-AP, the ELISA plate was read out at 177 405 nm and obtained measuring values were used to generate calibration curves for SARS-CoV-2 178 specific antibody concentrations in PBS (Fig 1, black curve) and in human serum samples (Fig 1, red 179 curve). Same calibration measurements employing dilutions of SARS-CoV-2 specific antibody were 211 done with our PoC MInD-based setup (Fig 2 and 3) . Comparable to laboratory-based ELISA, the same 212 dilutions of SARS-CoV-2 spike protein peptide specific antibody in PBS-buffer (Fig 3, black cache = ./cache/cord-261718-zqoggwnk.txt txt = ./txt/cord-261718-zqoggwnk.txt === reduce.pl bib === id = cord-262276-5nue46dm author = Roussel, Yanis title = SARS-CoV-2: fear versus data date = 2020-03-19 pages = extension = .txt mime = text/plain words = 1860 sentences = 119 flesch = 55 summary = The first, severe acute respiratory syndrome (SARS) coronavirus, had very little impact on global morbidity and mortality, with more than 80 0 0 recognized cases and 774 deaths [15 , 16] . Among the Organisation for Economic Co-operation and Development (OECD) countries, 7476 patients have tested positive for SARS-CoV-2, with 96 deaths (mortality rate 1.3%) ( Table 3 ). In France, 191 people have tested positive for SARS-CoV-2, with three deaths (mortality rate 1.6%). If the extrapolation of deaths in AP-HM hospitals is correct, in metropolitan France, this would represent 543/0.8 * 100 = 67 875 cases of patients hospitalized with a respiratory infection with common coronaviruses in 2 months, which is almost as many cases as for SARS-CoV-2 worldwide. Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China cache = ./cache/cord-262276-5nue46dm.txt txt = ./txt/cord-262276-5nue46dm.txt === reduce.pl bib === id = cord-261075-wqtxhiy8 author = Zhang, Meng title = The nervous system——a new territory being explored of SARS-CoV-2 date = 2020-10-28 pages = extension = .txt mime = text/plain words = 3716 sentences = 216 flesch = 41 summary = However, there is growing evidence that SARS-CoV-2 can result in a broad spectrum of neurologic diseases (6) (7) (8) (9) , which is not surprising, as neurological manifestations have been reported in other respiratory viral infections, including coronavirus, but the nervous system manifestations of COVID-19 are more common and disabling, raising the worldwide concerns about its potential long-term complications to humans (10, 11) . In particular, we focused on its neurological manifestations and specific pathogenesis, as well as its comparison with other viral respiratory infections.Finally, we further summarized the significance of the neuroinvasion and the follow-up issues that need to be paid attention to by scientists, so as to help neurologists understand the influence of SARS-CoV-2 on nervous system better and promote the accurate diagnosis and efficient treatment of COVID-19. cache = ./cache/cord-261075-wqtxhiy8.txt txt = ./txt/cord-261075-wqtxhiy8.txt === reduce.pl bib === id = cord-266511-g5h4tazp author = Deslandes, A title = SARS-COV-2 was already spreading in France in late December 2019 date = 2020-05-03 pages = extension = .txt mime = text/plain words = 1369 sentences = 93 flesch = 58 summary = We report here a case of a patient hospitalized in December 2019 in our intensive care, of our hospital in the north of Paris, for hemoptysis with no etiological diagnosis and for which RT-PCR was performed retrospectively on the stored respiratory sample which confirmed the diagnosis of COVID-19 infection. After its onset in December 2019 in China, the new coronavirus (SARS-COV-2) spreads widely in several countries, causing COVID-19 illness. 8 Clinical symptomatology between COVID-19 and ILIis similar,we therefore decided retrospectively to look for SARS-COV2 in respiratory samples collected in the intensive care units (ICUs) of our hospital near Paris. We reviewed medical record of ICUs patients admitted for ILI between December 2, 2019 and January 16, 2020, with a negative RT-PCR performed at admission. Samples taken from patients with both ILI symptoms (fever higher than 38.5°C, cough, rhinitis, sore throat or myalgia) and ground glass opacity according to their medical record underwent SARS-COV-2 RT-PCR. cache = ./cache/cord-266511-g5h4tazp.txt txt = ./txt/cord-266511-g5h4tazp.txt === reduce.pl bib === id = cord-264267-weat0qs6 author = Kleine-Weber, Hannah title = Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus date = 2020-01-21 pages = extension = .txt mime = text/plain words = 7200 sentences = 325 flesch = 47 summary = Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. For host cell entry, the surface unit, S1, of MERS-CoV S binds to the cellular type-II transmembrane protein dipeptidyl peptidase 4 (DPP4, CD26) [15] . For the binding studies with solMERS-S1-Fc, a similar protocol was followed as described for the analysis of DPP4 surface expression with the exceptions that sol-MERS-S1-Fc was used instead of the primary antibody (1:10 dilution in PBS/BSA) and that an AlexaFluor488conjugated anti-human antibody (goat, 1:500 dilution in PBS/BSA, ThermoFisher Scientific) was employed as the secondary antibody. Reduced MERS-CoV S-driven host cell entry is caused by inefficient S protein binding to DPP4 harboring polymorphic amino acid residues. cache = ./cache/cord-264267-weat0qs6.txt txt = ./txt/cord-264267-weat0qs6.txt === reduce.pl bib === id = cord-265329-bsypo08l author = van Dorp, Lucy title = Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 date = 2020-05-05 pages = extension = .txt mime = text/plain words = 4915 sentences = 270 flesch = 49 summary = Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. The extraordinary availability of genomic data during the COVID-19 pandemic has been made possible thanks to a tremendous effort by hundreds of researchers globally depositing SARS-CoV-2 assemblies (Table S1 ) and the proliferation of close to real time data visualisation and analysis tools including NextStrain (https://nextstrain.org) and CoV-GLUE (http://cov-glue.cvr.gla.ac.uk). In this work we use this data to analyse the genomic diversity that has emerged in the global population of SARS-CoV-2 since the beginning of the COVID-19 pandemic, based on a download of 7710 assemblies. The genomic diversity of the global SARS-CoV-2 population being recapitulated in multiple countries points to extensive worldwide transmission of COVID-19, likely from extremely early on in the pandemic. cache = ./cache/cord-265329-bsypo08l.txt txt = ./txt/cord-265329-bsypo08l.txt === reduce.pl bib === id = cord-252456-971d0sir author = Hemida, Maged Gomaa title = The SARS-CoV-2 outbreak from a one health perspective date = 2020-03-16 pages = extension = .txt mime = text/plain words = 4824 sentences = 244 flesch = 55 summary = The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. Currently, the case fatality rate is relatively low (⁓3.6%) compared to infections with severe acute respiratory syndrome coronavirus (SARS-CoV, (10%) and MERS-CoV (32%) [11] . Based on the previous emergence history of SARS-CoV, the presence of a large number of mammals and birds overcrowded in one place may give a chance for pathogens, particularly those with RNA genomes such as coronaviruses and influenza viruses, to emerge. Based on the previous experience from the other emerging diseases, particularly SARS-CoV and influenza viruses, avoiding the mixing of various species of animals, birds, and mammals, is highly suggested [51, 65, 66] . The process of decontamination of the virus-contaminated surfaces by the appropriate disinfectants or virucidal agents was successful in case of other respiratory viruses such as SARS-CoV and avian influenza [59] . cache = ./cache/cord-252456-971d0sir.txt txt = ./txt/cord-252456-971d0sir.txt === reduce.pl bib === === reduce.pl bib === id = cord-264031-0y7xbgun author = Wierbowski, Shayne D. title = A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date = 2020-10-13 pages = extension = .txt mime = text/plain words = 5066 sentences = 291 flesch = 42 summary = title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. cache = ./cache/cord-264031-0y7xbgun.txt txt = ./txt/cord-264031-0y7xbgun.txt === reduce.pl bib === id = cord-266348-tbr2ynx0 author = Stroemer, A. title = Diagnostic accuracy of six commercial SARS-CoV-2 IgG/total antibody assays and identification of SARS-CoV-2 neutralizing antibodies in convalescent sera date = 2020-06-17 pages = extension = .txt mime = text/plain words = 2893 sentences = 215 flesch = 61 summary = Here, we compare the diagnostic accuracy of six commercially available SARS-CoV-2 IgG (Abbott SARS-CoV-2 IgG; Diasorin Liaison SARS-CoV-2 S1/2 IgG; Epitope EDI Novel Coronavirus COVID-19 IgG ELISA Kit; Euroimmun Anti-SARS-CoV-2 ELISA (IgG); Mikrogen recomWell SARS-CoV-2 IgG) or total SARS-CoV-2 antibody assays (Roche Elecsys Anti-SARS-CoV-2). The majority of assay results were confirmed in a laboratory-developed plaque reduction neutralization test and by a SARS-CoV-2 IgG-specific line assay including measurement of generally low IgG avidities (Mikrogen recomLine Coronavirus IgG [Aviditaet], prototype). Out 132 of the remaining 34 samples, only one serum (#20; Figure 1 ) which was obtained ten days after a positive 133 RT-PCR was tested negative for SARS-CoV-2 IgG/total antibodies in the six assays. Six of them -including three family members of a 153 confirmed COVID-19 case (#22; Figure 1 ) -were classified SARS-CoV-2 IgG/total antibody positive by the 154 majority of the tests. cache = ./cache/cord-266348-tbr2ynx0.txt txt = ./txt/cord-266348-tbr2ynx0.txt === reduce.pl bib === id = cord-262266-m0fjt483 author = Peddu, Vikas title = Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization date = 2020-05-07 pages = extension = .txt mime = text/plain words = 1847 sentences = 110 flesch = 53 summary = METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Eight unique patient samples consisting of six positive and two negative cases of suspected SARS-CoV-2 were sequenced using RNA extracted for a qRT-PCR diagnostic assay. Despite our reference database not containing any SARS-CoV-2 genomes, the six samples that were positive for SARS-CoV-2 by qRT-PCR had reads classified to Table 2) . Phylogenetic analysis revealed that the six SARS-CoV-2 sequences found cluster within two clades representing the Washington state and European outbreaks. cache = ./cache/cord-262266-m0fjt483.txt txt = ./txt/cord-262266-m0fjt483.txt === reduce.pl bib === id = cord-262119-s6hc7fxs author = Ostaszewski, Marek title = COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date = 2020-10-27 pages = extension = .txt mime = text/plain words = 12332 sentences = 742 flesch = 38 summary = title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms cache = ./cache/cord-262119-s6hc7fxs.txt txt = ./txt/cord-262119-s6hc7fxs.txt === reduce.pl bib === id = cord-263481-w5ytp1q7 author = Lokman, Syed Mohammad title = Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach date = 2020-06-02 pages = extension = .txt mime = text/plain words = 3013 sentences = 171 flesch = 54 summary = MERS-CoV uses dipeptidyl peptidase-4 (DPP4) as entry receptor [11] whereas SARS-CoV and SARS-CoV-2 utilize ACE-2 (angiotensin converting enzyme-2) [12] , abundantly available in lung alveolar epithelial cells and enterocytes, suggesting S glycoprotein as a potential drug target to halt the entry of SARS-with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. cache = ./cache/cord-263481-w5ytp1q7.txt txt = ./txt/cord-263481-w5ytp1q7.txt === reduce.pl bib === === reduce.pl bib === id = cord-257105-vrwuaknf author = Davies, Julie title = Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19 date = 2020-09-15 pages = extension = .txt mime = text/plain words = 2642 sentences = 141 flesch = 47 summary = Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. This study presents a detailed in silico analysis of the expression of nrP1 in the human brain, highlighting the potential role of nrP1 as an additional SarS-coV-2 infection mediator in the CNS via NRP1-expressing cells. Given this newly identified role of nrP1 in enhancing SarS-coV-2 entry into the cnS, characterizing the precise expression of nrP1 in the human brain becomes important in the context of the neurologic involvement of coVid-19. Finally, the parolfactory gyri which receive inputs from the olfactory bulb and provide input to the limbic system, also exhibit nrP1 expression, and so their potential involvement in the SarS-coV-2 infection of the cnS merits further research. cache = ./cache/cord-257105-vrwuaknf.txt txt = ./txt/cord-257105-vrwuaknf.txt === reduce.pl bib === id = cord-265366-vmuqbpkk author = Leibowitz, Jill title = Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without SARS-CoV-2 Infection date = 2020-10-09 pages = extension = .txt mime = text/plain words = 2626 sentences = 142 flesch = 54 summary = 7, 8, 9, 10, 11, 12, 13 The largest case series to date describes 18 infants younger than 90 days of age who tested positive for SARS-CoV-2, 14 of whom were febrile. 9 The objective of this study was to compare the clinical and demographic characteristics and hospital course of febrile infants who presented to Cohen Children's Medical Center (CCMC) during March and April of 2020, the time period of peak COVID-19 incidence in our region, to febrile infants treated in CCMC during March and April of previous years. The key findings of our study are that during the peak of the COVID-19 pandemic in New York, SARS-CoV-2 was the predominant pathogen identified among febrile infants younger than 57 days of age, and the disease was self-limited in all infants with COVID-19. 26 Infants with COVID-19 presented with lethargy and feeding difficulty more with SARS-CoV-2 infection among infants younger than 90 days of age. cache = ./cache/cord-265366-vmuqbpkk.txt txt = ./txt/cord-265366-vmuqbpkk.txt === reduce.pl bib === id = cord-262045-r2iqpmmc author = Smits, Saskia L. title = Reliable typing of MERS-CoV variants with a small genome fragment date = 2014-12-15 pages = extension = .txt mime = text/plain words = 2151 sentences = 110 flesch = 49 summary = RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. In addition, the MERS-CoV variant typing assay was performed on camel samples from a slaughterhouse in Qatar [13] and sequences for 14 MERS-CoV positive animals with cycle threshold values ranging from 12.9 to 32.2 as determined by UpE real time RT-PCR [17, 18] were obtained (Fig. 2) . Subsequent analyses revealed a region in the open reading frame that encodes the spike protein with a number of positions in which nucleotide variation occurs between MERS-CoV variants with a strong phylogenetic signal regarding previously identified clusters of viruses based on full-length MERS-CoV genomes. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia cache = ./cache/cord-262045-r2iqpmmc.txt txt = ./txt/cord-262045-r2iqpmmc.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-264814-v4wnmg03 author = Flanagan, Katie L. title = Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date = 2020-10-02 pages = extension = .txt mime = text/plain words = 15130 sentences = 700 flesch = 44 summary = Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. cache = ./cache/cord-264814-v4wnmg03.txt txt = ./txt/cord-264814-v4wnmg03.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-267887-ntwvquqz author = Yang, Ren title = Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro date = 2020-08-21 pages = extension = .txt mime = text/plain words = 1308 sentences = 81 flesch = 51 summary = title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro Previously, researchers had developed a pseudotyped virus system for SARS-CoV and MERS-CoV, based on HIV-1 core, bearing virus spike protein. Furthermore, the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples from convalescent patients. In conclusion, we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory. Development and optimization of a sensitive pseudovirus-based assay for HIV-1 neutralizing antibodies detection using A3R5 cells A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig cache = ./cache/cord-267887-ntwvquqz.txt txt = ./txt/cord-267887-ntwvquqz.txt === reduce.pl bib === id = cord-268034-7id7sfsu author = Auerswald, Heidi title = Assessment of Inactivation Procedures for SARS-CoV-2 date = 2020-05-28 pages = extension = .txt mime = text/plain words = 1620 sentences = 100 flesch = 47 summary = This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. The buffers used in this lysis step yield varying results [11, 13, 15, 16] ; however, unlike 224 previous studies [11] , this study found that AVL buffer alone was successfully able to fully 225 inactivate up to 5 log10 of virus from three different primary isolates of SARS-CoV-2. Previous 234 studies have shown that GITC-lysis buffers are able to inactivate SARS-CoV-2 samples [11, 12] ; 235 however, the addition of Triton-X may be necessary for complete inactivation [11] . Therefore, formaldehyde treatment does not appear to be a 247 solution for increased molecular SARS-CoV-2 testing; however, it does remain a viable alternative 248 for sample inactivation or disinfection. cache = ./cache/cord-268034-7id7sfsu.txt txt = ./txt/cord-268034-7id7sfsu.txt === reduce.pl bib === id = cord-268476-3lxsh1zz author = Skoog, Hunter title = Tracheotomy in the SARS‐CoV‐2 pandemic date = 2020-04-29 pages = extension = .txt mime = text/plain words = 1504 sentences = 91 flesch = 44 summary = The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. The severe acute respiratory syndrome (SARS)-CoV-2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. Our priorities in establishing these guidelines included: optimal patient care, protection of medical personnel, minimizing further spread of the virus and preservation of important resources (ICU beds, ventilators, and PPE). Due to the paucity of data regarding the current SARS-CoV-2 epidemic, the literature from the SARS epidemic of In Canada, 43% of cases occurred in health care workers as a result of AGPs. 1,2 One instance involved a difficult intubation of a patient who was under investigation for SARS. There are multiple reports 3,4 of safely performing tracheotomy on patients with SARS without infecting health care workers. cache = ./cache/cord-268476-3lxsh1zz.txt txt = ./txt/cord-268476-3lxsh1zz.txt === reduce.pl bib === id = cord-270550-if748w2n author = Bailey, Adam L. title = SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date = 2020-11-05 pages = extension = .txt mime = text/plain words = 5808 sentences = 440 flesch = 49 summary = To ascertain whether human pluripotent stem cell-derived cardiomyocytes (hPSC-derived 150 CMs) can serve as an appropriate model to study cardiac SARS-CoV-2 infection, we measured 151 ACE2 mRNA expression in hPSC-derived CMs. Quantitative RT-PCR revealed that hPSC-152 derived CMs abundantly expressed ACE2 mRNA. We identified numerous host genes that were differentially 226 regulated upon SARS-CoV-2 infection in each of the examined cell types and two-dimensional 227 tissues (Fig. 3c) . 236 GO pathway analysis revealed that infected hPSC-derived CMs and two-dimensional co-237 culture tissues showed upregulation of genes associated with immune cell activation, stress-238 induced transcription, and responses to pathogens including viruses. Consistent with the 343 possibility that disrupted sarcomere gene expression might contribute to reduced EHT 344 contractility, immunostaining of hPSC-derived CMs infected with SARS-CoV-2 revealed evidence 345 of sarcomere loss 3 days following infection (Fig. 6c) , a time point that preceded cell death. cache = ./cache/cord-270550-if748w2n.txt txt = ./txt/cord-270550-if748w2n.txt === reduce.pl bib === id = cord-268483-joiajgs4 author = Shah, Vibhuti Kumar title = Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date = 2020-08-07 pages = extension = .txt mime = text/plain words = 10644 sentences = 477 flesch = 43 summary = As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. An ELISA-based time kinetics study to detect the COVID-19 specific humoral immune response showed that the patients produced IgM and IgG antibodies that did not cross-react with other human coronaviruses except SARS-CoV. A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65) . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice cache = ./cache/cord-268483-joiajgs4.txt txt = ./txt/cord-268483-joiajgs4.txt === reduce.pl bib === id = cord-269275-b7xxk48t author = Tang, Xiaojia title = Neurological manifestations in COVID-19 and its possible mechanism date = 2020-09-27 pages = extension = .txt mime = text/plain words = 4631 sentences = 260 flesch = 44 summary = SARS-CoV-2 has been reported to be associated with Guillain-Barré syndrome, rhabdomyolysis, acute cerebrovascular disease, central nervous system infections and other neurological diseases. Four formal reports have described neurological problems in SARS patients, including polyneuropathy [35] , myopathy and rhabdomyolysis [36] , large artery ischemic stroke [37] and central nervous system infections [38] . In a study by Mao et al., 214 patients diagnosed with COVID-19 were enrolled, and six (2.80%) of them developed acute cerebrovascular disease (five cases of ischemic stroke and one case of cerebral hemorrhage). Strokes are not uncommon in critically ill patients with multiple comorbidities, so SARS-CoV-2 infections in humans may increase the risk of stroke. Since some COVID-19 patients have complained of headaches, nausea etc, care providers should be alert for central nervous system infections caused by SARS-CoV-2 if such patients also exhibit symptoms such as a fever, epilepsy and disturbances of consciousness. cache = ./cache/cord-269275-b7xxk48t.txt txt = ./txt/cord-269275-b7xxk48t.txt === reduce.pl bib === id = cord-270116-r2rnnsfh author = Lippi, Giuseppe title = Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) date = 2020-05-11 pages = extension = .txt mime = text/plain words = 4742 sentences = 192 flesch = 37 summary = As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Recent studies have also been published on the possibility to use rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for SARS-CoV-2 detection, but additional evidence is needed at this point in time for validating their routine usage in COVID-19 diagnostics (38, 39) . As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. cache = ./cache/cord-270116-r2rnnsfh.txt txt = ./txt/cord-270116-r2rnnsfh.txt === reduce.pl bib === id = cord-270396-3bcnnyfq author = Karacin, Cengiz title = How does COVID-19 fear and anxiety affect chemotherapy adherence in patients with cancer date = 2020-07-17 pages = extension = .txt mime = text/plain words = 3605 sentences = 177 flesch = 57 summary = Aim: To investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy adherence in patients with cancer. Data on patients' age, sex, comorbidities, history of smoking, marital status, number of children, educational background, place of residence and household, cancer type, disease stage, CT regimen and date of CT postponement were obtained from the hospital records. In the present study, it was seen that the CT postponement rate increased significantly following the first COVID-19 case in Turkey and COV-FA was identified as the third most frequent reason for CT postponement. In the present study, the median TCBT of the patients who postponed CT due to COV-FA was 47 days (range . • We aimed to investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy (CT) adherence in patients receiving active CT for cancer, and to identify the characteristics of patients who postponed their CT due to COV-FA, as well as the time to come back to treatment (TCBT) and the factors affecting TCBT in these patients. cache = ./cache/cord-270396-3bcnnyfq.txt txt = ./txt/cord-270396-3bcnnyfq.txt === reduce.pl bib === id = cord-269289-6uog10j4 author = Mabillard, Holly title = Electrolyte Disturbances in SARS-CoV-2 Infection date = 2020-07-22 pages = extension = .txt mime = text/plain words = 5684 sentences = 289 flesch = 44 summary = These include additional respiratory complications (pulmonary fibrosis -reported in 21% of those hospitalised with SARS-CoV-2 9 months post-discharge in one study 3 ) 7 , cardiovascular complications (acute cardiac injury (7% 8 ), cardiomyopathy (1/3 patients 9 ), cardiac tamponade, heart failure, dysrhythmias (17% 8 ) and venous thromboembolic events (20% 10 )) 11 , neurological complications (myopathy, acute stroke (5.7% of those with severe infection 12 ), Guillain-Barre syndrome (0.4% hospitalised patients 11 ) and encephalopathy) 13 , acute liver and/or pancreatic injury (29% and 17% respectively in one cohort) 14 , cytokine storm syndrome, septic shock, DIC, diarrhoea, Kawasaki-like disease 14 and renal complications (acute tubular injury, rhabdomyolysis, proteinuria, secondary focal segmental glomerulosclerosis and possible renin-angiotensinaldosterone system activation) 15 . The study reported that the degree of hypokalaemia correlated with severity of SARS-CoV-2 symptoms and they suggested that hypokalaemia can be difficult to correct as seen in two patients because the renal potassium wasting persists until clinical recovery from the virus. cache = ./cache/cord-269289-6uog10j4.txt txt = ./txt/cord-269289-6uog10j4.txt === reduce.pl bib === id = cord-268468-036i1082 author = Asif, Muhammad title = The role of biosensors in COVID-19 outbreak date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3204 sentences = 189 flesch = 43 summary = In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor and surface plasmon resonance biosensors in the detection of SARS-CoV-2 has been underscored. In this outbreak, three different types of diagnosis tests are being used including (i) chest CT scan along with clinical indications, (ii) RNA detection using RT-PCR assay and (iii) lateral flow assays, full automatic chemiluminescence method, enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies [5] . In this review, we have summarized the biosensor based technologies which are able to detect SARS-CoV-2 effectively. The peptide monolayer was successfully coated on SPR biosensor and further functionalized with virus nucleocapsid protein which was finally able to detect SARS-CoV-2 antibodies at nanomolar level. The sensing aptitude of the biosensor was evaluated employing antigen protein, self-cultured virus, and nasopharyngeal swab samples taken from people infected with COVID-19 pneumonia. cache = ./cache/cord-268468-036i1082.txt txt = ./txt/cord-268468-036i1082.txt === reduce.pl bib === id = cord-270533-s2d3q4ob author = Lau, Yu-Lung title = SARS: future research and vaccine date = 2004-11-05 pages = extension = .txt mime = text/plain words = 3000 sentences = 167 flesch = 47 summary = Severe acute respiratory syndrome (SARS), a newly emerged infectious disease of humans in the 21st century, appeared in Guangdong Province in Southern China in November 2002 and spread to 26 countries on five continents along international air travel routes, causing large scale outbreaks in Hong Kong, Singapore and Toronto in early 2003. This novel CoV has satisfied Koch's postulates for causation by its consistent isolation from SARS patients, viral isolation, reproduction of disease in non-human primates after inoculation and the presence of specific antibody response against the virus in both patients and experimentally infected primates 8 . Indeed, sporadic reemergence of cases have been reported in Guangdong Province as well as from research laboratories Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. cache = ./cache/cord-270533-s2d3q4ob.txt txt = ./txt/cord-270533-s2d3q4ob.txt === reduce.pl bib === id = cord-268388-kkhuzf3p author = Sharif-Yakan, Ahmad title = Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date = 2014-12-04 pages = extension = .txt mime = text/plain words = 2507 sentences = 141 flesch = 50 summary = Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study cache = ./cache/cord-268388-kkhuzf3p.txt txt = ./txt/cord-268388-kkhuzf3p.txt === reduce.pl bib === id = cord-274399-cd7cmpoj author = Barzin, Amir title = SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3304 sentences = 189 flesch = 47 summary = This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This study identifies a very limited seroprevalence of SARS-CoV-2 among asymptomatic individuals accessing the UNC Health system. This study employed an EUA assay performed in a CLIA-certified laboratory on a venous blood sample, with demonstrated specificity to detect antibodies only to SARS-CoV-2, not to seasonal coronaviruses. Upon arrival for SARS-CoV-2 Seroprevalence in North Carolina ® routine care or scheduled visits for enrollment into the study, patients performed a consent procedure that included reviewing recent COVID-19 clinical history using UNC IRB-approved questionnaires. cache = ./cache/cord-274399-cd7cmpoj.txt txt = ./txt/cord-274399-cd7cmpoj.txt === reduce.pl bib === id = cord-271243-8cfyen86 author = Xiao, Y. title = Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus date = 2008-05-31 pages = extension = .txt mime = text/plain words = 3375 sentences = 179 flesch = 52 summary = title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). The present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. One animal from each group was sacrificed at 3, 13, 23, 34 and 35 days post-infection (dpi), and lung, spleen, lymph node, small intestine, kidney, trachea, cerebrum, pancreas, sex glands, stomach and heart were collected from each animal. In summary, the data presented in this study further corroborate previous findings (Wu et al., 2005) in demonstrating that civets are more susceptible to SARS-CoV infection than other animals, as implied by their clinical symptoms, pathological changes and virus distribution within tissues. cache = ./cache/cord-271243-8cfyen86.txt txt = ./txt/cord-271243-8cfyen86.txt === reduce.pl bib === id = cord-272113-j82z4q8x author = Akaji, Kenichi title = Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease date = 2020-08-27 pages = extension = .txt mime = text/plain words = 6459 sentences = 281 flesch = 45 summary = Instead of an exhaustive survey of the inhibitors [21] , we provide an overview of several typical inhibitors, and our recent efforts for the rational design of new scaffolds are discussed based on the inhibitory mechanism and structural interactions with SARS-CoV 3CL pro . Following the interaction with the active center of the SARS-CoV 3CL pro , the nucleophilic Cys145 thiolate generated by a proton-withdrawing effect caused by His41 at the catalytic dyad promotes a typical 1,4-addition to the α,β-unsaturated structure of the Michael acceptor ( Figure 3 ). These data also indicate that the corresponding S1 pocket of the SARS-CoV 3CL pro might accept a simple ring structure containing heteroatoms at this specific interaction site, which provides a clue to our design of a potent substrate-based inhibitor described later in this review. cache = ./cache/cord-272113-j82z4q8x.txt txt = ./txt/cord-272113-j82z4q8x.txt === reduce.pl bib === id = cord-271781-cfv0ta10 author = Patel, Kishan P. title = Transmission of SARS-CoV-2: an update of current literature date = 2020-07-07 pages = extension = .txt mime = text/plain words = 4469 sentences = 232 flesch = 47 summary = To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Additionally, studies have noted that its fecal-oral transmission potential may lie in the fact that prolonged viral shedding can occur in fecal matter-one case reported an asymptomatic COVID-19 patient experiencing viral detection in the stool for up to 42 days, while nasopharyngeal sampling was negative [31] . To oppose, in a retrospective review of nine COVID-19 pregnant mothers who underwent cesarean section, six patients had samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples tested for SARS-CoV-2, and all were negative [43] . cache = ./cache/cord-271781-cfv0ta10.txt txt = ./txt/cord-271781-cfv0ta10.txt === reduce.pl bib === id = cord-271648-m2c5bvuj author = Ashour, Hossam M. title = Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks date = 2020-03-04 pages = extension = .txt mime = text/plain words = 7536 sentences = 401 flesch = 56 summary = Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. However, unlike SARS-CoV, human-to-human transmission of MERS-CoV is not easy and has not been confirmed except in cases of very close contact with infected patients in health care settings [67] . Similar to the adaptation of SARS-CoV to human host, MERSr-CoVs that are circulating in bats had to undergo several amino acid changes in RBD of S protein to become capable of infecting camels and humans ( Figure 2 ) [74] . S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model cache = ./cache/cord-271648-m2c5bvuj.txt txt = ./txt/cord-271648-m2c5bvuj.txt === reduce.pl bib === id = cord-272010-kc0gi3cj author = Anand, Sai Priya title = Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3661 sentences = 216 flesch = 56 summary = The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 cache = ./cache/cord-272010-kc0gi3cj.txt txt = ./txt/cord-272010-kc0gi3cj.txt === reduce.pl bib === id = cord-268718-tt07cwrf author = Tan, Heng Wee title = Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection date = 2020-06-30 pages = extension = .txt mime = text/plain words = 6346 sentences = 400 flesch = 52 summary = 54 Virus infectivity study has indicated that the SARS-CoV-2 is able to utilize ACE2 of human, Chinese horseshoe bats, civet, and pig but was not able to use mouse ACE2. The roles of ACE2 expression in SARS-CoV-2 pathogenesis and human COVID-19 susceptibility are largely unknown. B, ACE2 expression in lung cancer patients with different smoking histories analyzed using similar methods as described previously 106 other symptoms in addition to respiratory symptoms, suggesting that SARS-CoV-2 could perhaps infect other organs (Figure 3 ). 118 In addition to sputum, SARS-CoV-2 RNA has been detected in the stools of a COVID-19 patient, 119 F I G U R E 3 Tissue distribution of angiotensin-converting enzyme 2 (ACE2) expression and potential COVID-19 susceptibility. Expression of elevated levels of proinflammatory cytokines in SARS-CoV-infected ACE2 + cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS cache = ./cache/cord-268718-tt07cwrf.txt txt = ./txt/cord-268718-tt07cwrf.txt === reduce.pl bib === id = cord-268540-wrjzr3ws author = Park, You Jeong title = Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics date = 2020-08-13 pages = extension = .txt mime = text/plain words = 16363 sentences = 868 flesch = 45 summary = A potential target for drug development for COVID-19 also involves inhibition of ACE2, the host cell receptor for the S protein of SARS-CoV-2 that is primed by TMPRSS2 protease and may prevent the entry of the virus. As previously described, the intermolecular interaction between the viral SP and human ACE2 Phase II CAStem cells will be intravenously injected into patients with or without acute respiratory distress syndrome (ARDS) induced by COVID-19. Phase II Patients with acute respiratory distress syndrome caused by COVID-19 will be treated with intravenous UC-MSCs at a dose 1 million xKg. Patient improvement will be evaluated over three weeks, along with the assessment of the immune profile, investigating the stem cells' effect on the cytokine storm. The similarities in systemic multi-organ complications between H7N9 and Sars-Cov-2 infections, along with direct evidence of the benefits of MSCs transplantation for COVID-19, further supports the potential of stem cells as an effective treatment [138] . cache = ./cache/cord-268540-wrjzr3ws.txt txt = ./txt/cord-268540-wrjzr3ws.txt === reduce.pl bib === id = cord-271505-eot38721 author = Wang, Hongliang title = Molecular pathogenesis of severe acute respiratory syndrome date = 2006-09-28 pages = extension = .txt mime = text/plain words = 4959 sentences = 229 flesch = 48 summary = demonstrated that the angiotensin-converting enzyme 2 (ACE2) is a functional cellular receptor of SARS-CoV, by using coimmunoprecipitation of the virus glycoprotein (S1) with lysates from cells that are susceptible to virus infection (Vero E6 cells) followed by mass spectrometry analysis [7] . In the case of SARS, apoptosis was observed in patients' lung epithelial cells; thus, SARS-CoV induced apoptosis would certainly have a deleterious pathogenic role, leading to severe tissue damage [26] . This model system allowed us to avoid possible secondary effects resulting from viral replication or infections in vivo and to directly test whether SARS-CoV spike protein might adversely affect acute lung injury through modulation of ACE2. SARS-CoV infection or spike protein treatment can down-regulate the expression of ACE2, and thus aggravate lung injury. Nabel, pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN cache = ./cache/cord-271505-eot38721.txt txt = ./txt/cord-271505-eot38721.txt === reduce.pl bib === id = cord-272654-hh29olk7 author = Bošnjak, Berislav title = Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods date = 2020-11-02 pages = extension = .txt mime = text/plain words = 6111 sentences = 414 flesch = 54 summary = We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Similarly, anti-SARS-CoV-2 S IgA antibodies were present in 33/37 (89.2%) of the tested sera; two samples were diagnosed as borderline positive and two as negative Fig. 1 Qualitative analysis of serum total IgG (A) and IgA (B) antibodies against SARS-CoV-2 S1 in convalescent patients with mild or severe COVID-19 and healthy controls (HC) determined by ELISA. The median sVNT titer of the mildly affected convalescent cohort was 1:180, indicating that patients with mild COVID-19 produce relatively low amounts of SASRS-CoV-2 neutralizing antibodies (Fig. 2H ). This hypothesis is further supported by a positive correlation between the duration of symptoms and total anti-SARS-CoV-2 IgG, but not IgA, antibodies in convalescent patients with mild disease (Fig. 5A, B) . cache = ./cache/cord-272654-hh29olk7.txt txt = ./txt/cord-272654-hh29olk7.txt === reduce.pl bib === id = cord-274141-vujx538o author = Chinsembu, Kazhila C. title = Coronaviruses and Nature’s Pharmacy for the Relief of Coronavirus Disease 2019 date = 2020-10-06 pages = extension = .txt mime = text/plain words = 11338 sentences = 676 flesch = 53 summary = De Clercq (2005 suggested that it was feasible to develop SARS-CoV fusion inhibitors analogous to enfuvirtide, a linear 36-amino acid synthetic peptide marketed under the trade name Fuzeon, an approved anti-HIV drug that inhibits the entry of the virus into cells. It was hypothesized that specific flavonoids, such as quercetin, hesperetin, and myricetin (7) and their glycosylated derivatives, may play an effective role in inhibiting SARS-CoV entry into host cells, specifically by binding with high affinity to the spike protein, helicase, and protease sites on the ACE receptor (Ngwa et al. Although the ongoing SARS-CoV-2 global pandemic should remind scientists that current options for treating life-threatening zoonotic coronavirus infections are very limited , medicinal plants offer a strong pipeline for the discovery of novel lead compounds that can be converted into new drugs to treat COVID-19. cache = ./cache/cord-274141-vujx538o.txt txt = ./txt/cord-274141-vujx538o.txt === reduce.pl bib === id = cord-273451-xnce010o author = Salisbury-Afshar, Elizabeth M. title = Vulnerable Populations: Weathering the Pandemic Storm date = 2020-04-22 pages = extension = .txt mime = text/plain words = 1658 sentences = 97 flesch = 47 summary = Yet, even with awareness that all individuals deserve access to services, and that supporting marginalized populations will slow the spread of SARS-CoV-2, resource limitations will demand difficult allocation determinations. 3 Many individuals experiencing homelessness with SARS-CoV-2 will not meet hospitalization criteria and will be discharged into the general population. 11 In response to SARS-CoV-2, the Substance Abuse and Mental Health Services Administration has developed emergency regulations to support medication for opioid use disorder via telehealth, 12 and temporarily waived the requirement for in-person physical exam to be able to initiate buprenorphine. These often forgotten populations-people incarcerated, homeless, or using drugs-are likely to experience higher risk of exposure to SARS-CoV-2 because of their social circumstances. Planning should incorporate dedicated efforts, funding, and policies/guidelines specific to individuals who experience homelessness, are incarcerated, or are coping with substance use disorders both because these populations deserve care and services, and because not doing so poses great risk to the broader community. cache = ./cache/cord-273451-xnce010o.txt txt = ./txt/cord-273451-xnce010o.txt === reduce.pl bib === id = cord-274506-fzcuu4ma author = Jo, Seri title = Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors date = 2019-09-12 pages = extension = .txt mime = text/plain words = 4210 sentences = 247 flesch = 51 summary = While PLpro cuts the first three cleavage sites of its polyprotein, 3CLpro is responsible for cleavage of the remaining eleven locations resulting in release of a total of 16 non-structural proteins (nsp) in both SARS-and MERS-CoVs. The homodimeric form of 3CLpro is active in the presence of substrates. In this study, we used a proteolytic method to probe MERS-CoV 3CLpro inhibitory compounds with a synthetic peptide labelled with the EDANS-DABCYL FRET (Fluorescence resonance energy transfer) pair (Liu et al., 2005) . The proteolytic assay using MERS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The four compounds showed the severely reduced fluorescent intensity and thus represented their MERS-CoV 3CLpro inhibitory activity. In this study, we assayed the inhibitory activity of various flavonoids against MERS-CoV 3CLpro. The analysis of the four compounds with their homologs using an induced-fit docking study provided an insight of flavonoid scaffolds required to bind with MERS-CoV 3CLpro. cache = ./cache/cord-274506-fzcuu4ma.txt txt = ./txt/cord-274506-fzcuu4ma.txt === reduce.pl bib === id = cord-268206-ino9srb6 author = Hamed, Manal A. title = An overview on COVID-19: reality and expectation date = 2020-06-01 pages = extension = .txt mime = text/plain words = 6067 sentences = 330 flesch = 46 summary = Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. In the current SARS-COV-2 pandemic, Wu and McGoogan (2020) showed that patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 infection and mortality. The former (S) is the wild type which is milder while the latter (L) is the novel one which resulted in high binding affinity between SARS-COV-2 virus with angiotensin-converting enzyme 2 receptor in human cells. The use of convalescent plasma was recommended before as an important treatment during outbreaks of Ebola virus, Middle East respiratory syndrome coronavirus, SARS-COV-1, H5N1 avian influenza, and H1N1 influenza (Zhou et al. In a study involving patients with pandemic influenza (H1N1) and SARS virus, treatment of severe infection with convalescent plasma was associated with reduced respiratory viral load, serum cytokine response, and mortality (Cheng et al. cache = ./cache/cord-268206-ino9srb6.txt txt = ./txt/cord-268206-ino9srb6.txt === reduce.pl bib === id = cord-272603-nbosceoz author = Lin, Qiuyuan title = Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min date = 2020-07-02 pages = extension = .txt mime = text/plain words = 1882 sentences = 98 flesch = 42 summary = Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. 26 To meet the challenge of the large epidemic, we describe the development of a point-of-care microfluidic platform integrating a homemade fluorescence detection analyzer ( Figure 1A ), SARS-CoV-2 diagnostic microchips ( Figure 1B) , and multiple immunoassays ( Figure 1C ) for detecting three biomarkers (IgG, IgM, and antigen). This robust microfluidic immunoassay system can provide a useful tool for SARS-CoV-2 diagnosis in public health laboratories as well as for timely screening potentially infected patients to monitor and prevent the epidemic owning to its capability of easy, fast, cost-effective, and point-of-care detection. cache = ./cache/cord-272603-nbosceoz.txt txt = ./txt/cord-272603-nbosceoz.txt === reduce.pl bib === id = cord-274122-n9jnu2ah author = Mielech, Anna M. title = MERS-CoV papain-like protease has deISGylating and deubiquitinating activities date = 2014-02-01 pages = extension = .txt mime = text/plain words = 4845 sentences = 242 flesch = 51 summary = Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. In this study, we demonstrate the deISGylating and deubiquitinating (DUB) activities of the papain-like protease from MERS-CoV, and provide new information on the potential role of coronavirus protease/DUBs to inhibit the innate immune response. Our results suggest that PLpro might contribute to the modulation of innate immune responses upon SARS-CoV and MERS-CoV infection, however, the exact mechanism and the role of coronavirus PLPs and their associated DUB and deISGylating activities in these processes remains to be determined. cache = ./cache/cord-274122-n9jnu2ah.txt txt = ./txt/cord-274122-n9jnu2ah.txt === reduce.pl bib === id = cord-275454-an8xvow3 author = Clark, Andrew E title = Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Screening With Specimen Pools: Time to Swim, or Too Deep for Comfort? date = 2020-09-28 pages = extension = .txt mime = text/plain words = 1607 sentences = 87 flesch = 48 summary = We read with interest the study appearing in this issue by Li et al, who utilized a pooled sample strategy and a point-of-care (POC) reverse transcriptase-polymerase chain reaction (RT-PCR) assay for screening asymptomatic airline passengers arriving from areas of high SARS-CoV-2 prevalence. At the time of this writing, 2 reference laboratories in the United States (Quest Diagnostics and LabCorp) have received emergency use authorizations from the US Food and Drug Administration to use pooled specimens for SARS-CoV-2 detection [2] . In this work, pooling was performed in a 10:1 ratio, meaning 10 patient specimens were combined and tested using a single SARS-CoV-2 assay. At our institution, we are aware of patients who underwent preprocedure SARS-CoV2 screening utilizing the same assay deployed in this work, only to be diagnosed with active, symptomatic COVID-19 within 5 days of testing. cache = ./cache/cord-275454-an8xvow3.txt txt = ./txt/cord-275454-an8xvow3.txt === reduce.pl bib === id = cord-275138-033r259v author = Hayden, Frederick G title = Towards improving clinical management of Middle East respiratory syndrome coronavirus infection date = 2014-07-31 pages = extension = .txt mime = text/plain words = 1624 sentences = 78 flesch = 38 summary = Many agents have inhibitory activity in vitro for coronaviruses, including some licensed drugs, 7-9 but it is unclear whether their human pharmacology and tolerability would enable suffi cient doses to be given to exert antiviral eff ects in patients with MERS-CoV. 4 Ribavirin and interferon combinations are associated with modest Centre For Infections/Public Health England/Science Photo Library antiviral eff ects in MERS-CoV inoculated rhesus macaques given high doses. 7 For MERS-CoV, low neutralising antibody responses and inability to acquire suffi cient convalescent plasma from survivors with comorbidities might restrict the eff ectiveness of this treatment, although these limitations might not apply to infected health-care workers. With support as needed from international partners like WHO and ISARIC, 11 regional governments, and funders, Middle Eastern colleagues have both the opportunity and the responsibility to undertake studies to advance the understanding of eff ective prevention and treatment strategies for MERS-CoV and any future novel CoV outbreaks. cache = ./cache/cord-275138-033r259v.txt txt = ./txt/cord-275138-033r259v.txt === reduce.pl bib === id = cord-275565-xerr4vki author = Kumar, Manish title = Decay of SARS-CoV-2 RNA along the wastewater treatment outfitted with Upflow Anaerobic Sludge Blanket (UASB) system evaluated through two sample concentration techniques date = 2020-09-15 pages = extension = .txt mime = text/plain words = 3456 sentences = 230 flesch = 58 summary = For the first time, we present, i) an account of decay in the genetic material loading of SARS-CoV-2 during Upflow Anaerobic Sludge Blanket (UASB) treatment of wastewater, and ii) comparative evaluation of polyethylene glycol (PEG), and filtration as virus concentration methods from wastewater for the quantification of SARS-CoV-2 genes. Thus, there still remains questions pertaining to: i) capability of conventional WWTPs to reduce the abundance of SARS-CoV-2 RNA, ii) better understanding of the protocol, virus J o u r n a l P r e -p r o o f Journal Pre-proof precipitation through PEG and filtration which one is better methods for concentrating the samples before RNA isolation. Appraising the genetic loading reduction through Upflow Anaerobic Sludge Blanket (UASB) systems, and iii) Comparing the performances between PEG and filtration as virus concentration methods in terms of SARS-CoV-2 RNA sensitivity and inhibition removal. cache = ./cache/cord-275565-xerr4vki.txt txt = ./txt/cord-275565-xerr4vki.txt === reduce.pl bib === id = cord-268561-vq1uhj5i author = da Silva, Severino Jefferson Ribeiro title = Clinical and Laboratory Diagnosis of SARS-CoV-2, the Virus Causing COVID-19 date = 2020-08-04 pages = extension = .txt mime = text/plain words = 9916 sentences = 594 flesch = 47 summary = 11 The causative agent was identified as a novel CoV, eventually named SARS-CoV-2, and the respiratory syndrome associated with the infection was designated as coronavirus disease-2019 (COVID-19) by the World Health Organization (WHO). In direct tests, the clinical sample is examined directly for the presence of particles, virus antigens, or viral nucleic acids, whereas indirect methods detect the serological response against the infection (Figure 2 ). 11 Culture-based methods for SARS-CoV-2 detection have been used in research and public health laboratories in different parts of the world, but virus isolation is not recommended as a routine diagnostic procedure because it has low sensitivity, it is time-consuming, and it requires BSL-3 containment. 11 In addition to unequivocally confirming the diagnosis of a SARS-CoV-2 infection, regular sequencing of a percentage of patient samples from clinical cases can be used to monitor changes in the viral genome over time and trace transmission patterns. cache = ./cache/cord-268561-vq1uhj5i.txt txt = ./txt/cord-268561-vq1uhj5i.txt === reduce.pl bib === id = cord-273182-djb0ozrt author = Díez, José María title = Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date = 2020-09-09 pages = extension = .txt mime = text/plain words = 4326 sentences = 260 flesch = 50 summary = Recently, we reported cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2 and MERS-CoV with Flebogamma R DIF 5 and 10% and Gamunex R -C, two currently available intravenous IGs (IVIG) [23] . Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2 and MERS-CoV by: ELISA techniques; and well-established neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT 50 titers ranging from 4.5 to >5 (Figure 2 ). This neutralizing activity correlates with the cross-reactivity to different coronavirus antigens observed in ELISA-binding assays with IVIG, as shown in a previous study [23] . • Intravenous immunoglobulin products were tested against severe acute respiratory syndrome coronavirus 2 in cell culture neutralization assays. cache = ./cache/cord-273182-djb0ozrt.txt txt = ./txt/cord-273182-djb0ozrt.txt === reduce.pl bib === id = cord-274834-24v2b509 author = Lima, Rosiane title = Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children date = 2020-09-11 pages = extension = .txt mime = text/plain words = 5588 sentences = 268 flesch = 40 summary = Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. Specific questions that must be addressed revolve around the role children play in viral transmission, differences in pediatric viral susceptibility and immune responses, which could guide potential therapies for adults, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the development of severe hyperinflammatory shock and cardiac damage seen in Multisystem Inflammatory Syndrome in Children (MIS-C). In order to capture the full range of SARS-CoV-2 infection in the pediatric population, a COVID-19 biospecimen collection study was designed and implemented, including patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2-infected mothers, and asymptomatic children. cache = ./cache/cord-274834-24v2b509.txt txt = ./txt/cord-274834-24v2b509.txt === reduce.pl bib === id = cord-274841-rcdoewwv author = Tay, Matthew Zirui title = The trinity of COVID-19: immunity, inflammation and intervention date = 2020-04-28 pages = extension = .txt mime = text/plain words = 7186 sentences = 383 flesch = 43 summary = Monoclonal antibodies targeting the When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells expressing the surface receptors angiotensin-converting enzyme 2 (ACE2) and TMPRSS2, the active replication and release of the virus cause the host cell to undergo pyroptosis and release damageassociated molecular patterns, including ATP, nucleic acids and ASC oligomers. While there are no clinical trials specifically testing these drugs against COVID-19 at the time of writing, when camostat mesylate was tested on SARS-CoV-2 isolated from a patient, it prevented entry of the virus into lung cells 44, 50 . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Neutralizing antibodies in patients with severe acute respiratory syndrome-associated Nature reviews | Immunology coronavirus infection cache = ./cache/cord-274841-rcdoewwv.txt txt = ./txt/cord-274841-rcdoewwv.txt === reduce.pl bib === id = cord-275313-mfyff9ne author = Modjarrad, Kayvon title = Treatment strategies for Middle East respiratory syndrome coronavirus date = 2016-01-01 pages = extension = .txt mime = text/plain words = 3776 sentences = 174 flesch = 40 summary = Most recently, Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a novel cause of severe acute respiratory illness after first being identified in a Saudi Arabian patient in 2012 [2] . Much of the work to develop safe and effective MERS-CoV countermeasures has centred on vaccines, but the relatively low prevalence of the disease, the sporadic nature of the case clusters and the dearth of detailed knowledge on chains of transmission highlight the need for greater investments into the discovery of effective therapeutic and secondary prophylactic regimens for infected and exposed individuals. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection cache = ./cache/cord-275313-mfyff9ne.txt txt = ./txt/cord-275313-mfyff9ne.txt === reduce.pl bib === id = cord-275252-4e3cn50u author = Rad SM, Ali Hosseini title = Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date = 2020-05-16 pages = extension = .txt mime = text/plain words = 4368 sentences = 302 flesch = 53 summary = In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. A common primary focus of mutational analysis of emerging viruses is the alteration in amino acid sequence of viral proteins that may provide enhanced or new functions for virus replication, immune avoidance, or spread. However, the potential of these mutations to impact upon RNA structure and miRNA recognition provides a basis for ongoing monitoring of viral evolution at these sites in the SARS-CoV-2 genome. cache = ./cache/cord-275252-4e3cn50u.txt txt = ./txt/cord-275252-4e3cn50u.txt === reduce.pl bib === id = cord-275926-rj23z7po author = Fontanella, Marco M. title = Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey date = 2020-05-05 pages = extension = .txt mime = text/plain words = 4013 sentences = 234 flesch = 52 summary = 3. Institutional plans for the SARS-CoV-2 outbreak: any special measures adopted for SARS-CoV-2 positive neurosurgical patients were investigated, i.e. their screening rate and method, any changes in surgical indications, planning and activity for oncologic procedures, non-emergency surgeries, and subarachnoid hemorrhages (SAHs). The same correlation was found with regards to the medical perception of disease activity (Q2) in different countries, and only few respondents (3%) claimed their country was not facing the outbreak during the time period studied: among them, neurosurgeons from Germany were probably the most "wrong", since their country had between 10 4 to 10 5 SARS-CoV2 patients during the study period (Fig. 4A) . 5 India and Pakistan have been reported to be the world's best respondents to the SARS-COV-2 pandemic, 22-24 thus reflecting high rates of neurosurgical activity reorganizations. cache = ./cache/cord-275926-rj23z7po.txt txt = ./txt/cord-275926-rj23z7po.txt === reduce.pl bib === id = cord-274396-l611eisi author = Park, Su-Jin title = Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date = 2020-05-22 pages = extension = .txt mime = text/plain words = 4355 sentences = 208 flesch = 46 summary = While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. In order to determine the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine (HCQ) sulfate, or emtricitabine-tenofovir for treatment of SARS-CoV-2 infection, SARS-CoV-2 antibody-free ferrets (10/group) were inoculated with 10 5.8 50% tissue culture infective doses (TCID 50 )/ml of an NMC-nCoV02 strain through the intranasal (i.n.) route ( Fig. 1 ). Therefore, although clinical symptoms were attenuated in ferret groups treated with antiviral candidates, we also evaluated virus titers in respiratory and gastrointestinal tracts using nasal washes and stool samples, respectively, from SARS-CoV-2-infected ferrets. cache = ./cache/cord-274396-l611eisi.txt txt = ./txt/cord-274396-l611eisi.txt === reduce.pl bib === id = cord-275946-ofd2ipvs author = Cheng, Matthew P. title = Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review date = 2020-06-04 pages = extension = .txt mime = text/plain words = 5277 sentences = 282 flesch = 38 summary = Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. Appropriately designed seroepidemiologic studies will play an essential part in the public health response to the COVID-19 pandemic by characterizing transmission dynamics, refining disease burden estimates, and providing insight into the kinetics of humoral immunity to SARS-CoV-2. Serologic surveillance studies can also assess the accumulation of persons with antibody responses over time to estimate incidence of SARS-CoV-2 infection (57, 58) and can track age-and jurisdiction-specific disease susceptibility and identify at-risk populations (59) . cache = ./cache/cord-275946-ofd2ipvs.txt txt = ./txt/cord-275946-ofd2ipvs.txt === reduce.pl bib === id = cord-278522-e4qa19o6 author = Park, Se Yoon title = Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1605 sentences = 106 flesch = 56 summary = There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs Se Yoon Park 1 , Soon Gyu Yun 2 , Jeong Won Shin 2 , Bo Young Lee 3 , Hyo-Ju Son 1 , Seungjae Lee 1 , Eunjung Lee 1 , and Tae Hyong Kim 1 Since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than three million people in 211 countries. Few studies have investigated the duration of SARS-CoV-2 detection during the patients' recovery phase after resolution of COVID-19-associated symptoms/signs. SARS-CoV-2 shedding continued for about 4 weeks after resolution of COVID-19-associated symptoms/signs, with the longest period being 48 days. In conclusion, we found that SARS-CoV-2 virus shedding can persist for more than three weeks after resolution of COVID-19-associated symptoms/signs. cache = ./cache/cord-278522-e4qa19o6.txt txt = ./txt/cord-278522-e4qa19o6.txt === reduce.pl bib === id = cord-277841-7sp8ftbc author = Kumari, Pratibha title = Potential diagnostics and therapeutic approaches in COVID-19 date = 2020-08-12 pages = extension = .txt mime = text/plain words = 4873 sentences = 279 flesch = 45 summary = Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. COVID-19 is a contagious disease, caused by a novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2). In this article, we evaluated literature for reports informing various diagnostic methods, potential antiviral chemical therapeutics, and effective treatment strategies towards clinical management of COVID-19 patients. Molecular diagnostic methods target to detect either specific regions of the viral genome or RNA-dependent RNA polymerase (RdRP) and/or structural proteins of SARS-CoV-2 (Table 1) . Like most immunological diagnostic protocols, Enzyme-Linked Immunosorbent Assay (ELISA) for COVID-19 detection uses IgM and IgG antibody against nucleocapsid (N) and receptor binding domain spike proteins (S) of SARS-CoV-2. Table 2: Primers and probes for targeting SARS-Cov-2 genes in an RT-PCR test for COVID-19 diagnosis. cache = ./cache/cord-277841-7sp8ftbc.txt txt = ./txt/cord-277841-7sp8ftbc.txt === reduce.pl bib === id = cord-275690-83nrzfon author = Stanifer, Megan L. title = Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date = 2020-04-24 pages = extension = .txt mime = text/plain words = 4696 sentences = 256 flesch = 52 summary = title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, and in agreement with the results observed in cells depleted of the type III IFN receptor, this increase in infectivity was also associated with an increase in infectious denovo virus particle production ( Fig. 3G ). All together, these results strongly support a model where the type III IFN mediated signaling controls SARS-CoV-2 infection in human intestinal epithelial cells. All together these results show that human colon organoids can support SARS-CoV-2 infection, replication and spread and that the type III IFN response plays a critical role in controlling virus replication. cache = ./cache/cord-275690-83nrzfon.txt txt = ./txt/cord-275690-83nrzfon.txt === reduce.pl bib === id = cord-279443-2e4gz2bo author = Khan, Suliman title = Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns date = 2020-06-09 pages = extension = .txt mime = text/plain words = 4939 sentences = 245 flesch = 43 summary = To identify and select the papers in this review we searched the published research and review articles relevant to origin and outbreaks of three human coronaviruses, and features, transmission, spread, entry mechanisms, infectiousness, control strategies, and animals hosts for SARS-CoV-2. Although it is important to know about the symptoms' appearance and severity, however, understanding the transmission of the infection to healthy individuals from COVID-19 patients and zoonotic sources can be of great importance in the aspects of developing strategies to prevent and control the spread of COVID-19. This outbreak was reported to be caused by SARS-CoV, originated from market civets before its transmission and infection in humans (17) . Early claims came FIGURE 2 | The SARS-CoV-2 transmission from bats via unknown intermediate to humans causes infectiousness known as COVID-19 disease. According to the CDC report on coronavirus disease, individuals with underlying chronic medical conditions are at higher risk for contracting COVID-19 infection. cache = ./cache/cord-279443-2e4gz2bo.txt txt = ./txt/cord-279443-2e4gz2bo.txt === reduce.pl bib === id = cord-278362-pwi48i20 author = Khan, Abbas title = Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) date = 2020-06-18 pages = extension = .txt mime = text/plain words = 5136 sentences = 287 flesch = 55 summary = title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. In this study, the protein of SARS-COV-2 (3CLpro, also named 3-chymotrypsin-like protease) was subjected to drug repurposing and virtual screening for potent drug identification followed by molecular dynamics simulation and binding free energy calculation. In the current study, the repurposing of anti-HIV drugs against the SARS-COV-2 main protease was carried out using structure-based screening methods. In this study, based on the results of bioinformatics analysis, we targeted 3CLpro from SARS-COV-2 using drugs repurposing (anti-HIV drugs) virtual drugs screening (TCM) approaches to shortlist the most potent compounds for the possible treatment. cache = ./cache/cord-278362-pwi48i20.txt txt = ./txt/cord-278362-pwi48i20.txt === reduce.pl bib === id = cord-277487-jgbjxgh1 author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-06-20 pages = extension = .txt mime = text/plain words = 5057 sentences = 242 flesch = 53 summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. cache = ./cache/cord-277487-jgbjxgh1.txt txt = ./txt/cord-277487-jgbjxgh1.txt === reduce.pl bib === id = cord-280662-gakayv6e author = Bian, Jingwei title = Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator date = 2020-10-13 pages = extension = .txt mime = text/plain words = 5251 sentences = 308 flesch = 49 summary = Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. SARS-CoV-2 has been shown to share the same functional receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV) 4, 5 . SARS-CoV S-protein binding facilitates ADAM17-dependent ACE2 shedding and has been shown to induce viral entry into the cell 52 . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) cache = ./cache/cord-280662-gakayv6e.txt txt = ./txt/cord-280662-gakayv6e.txt === reduce.pl bib === id = cord-274802-7ioiwsd8 author = Varghese, Praveen Mathews title = Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies date = 2020-08-19 pages = extension = .txt mime = text/plain words = 19657 sentences = 1033 flesch = 42 summary = Proteomic and transcriptomic studies on bronchoalveolar lavage (BAL) samples from COVID-19 patients have also revealed considerable insights into the expression of SARS-CoV-2 receptors, co-receptors, immune responses, as well as risk factors for severe disease e.g. age and co-morbidities. Furthermore, treatment with a recombinant C5a antibody on 2 male COVID-19 patients aged 54 and 67 years showed significant benefit in suppressing complement hyperactivation, which contributes to the excessive immune response causing aggravated inflammatory lung injury, a hallmark of SARS-CoV-2 pathogenesis and lethality (242) . Consistent with endothelial injury, the significantly elevated levels of von Willebrand factor found in the patient with severe COVID-19 has led to the idea that the infection of the ACE2 expressing endothelium by SARS-CoV-2 induces injury and activates the complement , which sets up a feedback loop that maintains a state of inflammation (243, (268) (269) (270) . Initial clinical studies in China involving 100 SARS-CoV-2 infected patients, who were treated with Chloroquine, showed amelioration of pneumonia, shortened disease progression, increased resolution of lung lesions on CT, and a better virus-negative conversion (313, 314) . cache = ./cache/cord-274802-7ioiwsd8.txt txt = ./txt/cord-274802-7ioiwsd8.txt === reduce.pl bib === id = cord-276630-qci7khki author = Lima, William Gustavo title = The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review date = 2020-06-08 pages = extension = .txt mime = text/plain words = 3727 sentences = 214 flesch = 49 summary = Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. Only seven drugs (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, Table 1 Clinical evidence of potential candidates for drug repositioning against COVID-19 (SARS-CoV-2) *Lopinavir (400 mg) + ritonavir (100 mg), q12h, orally; associated with umifenovir (200 mg), q12h, orally. [14] reported that the use of arbidol in combination with lopinavir/ritonavir inhibits the aggravation of pneumonia caused by SARS-CoV-2 and promotes a virus-negative conversion in patients from China. Of these, only six drugs (lopinavir/ritonavir, umifenovir (arbidol), remdesivir, chloroquine, and hydroxychloroquine) have shown promising results in preclinical trials and have clinically lessened the symptoms of COVID-19. Although lopinavir/ ritonavir had low anti-SARS-CoV-2 activity, arbidol, remdesivir, and chloroquine/hydroxychloroquine showed promising effects against this coronavirus. cache = ./cache/cord-276630-qci7khki.txt txt = ./txt/cord-276630-qci7khki.txt === reduce.pl bib === id = cord-277253-vy0mvzeb author = Liu, Hongbo title = Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date = 2020-04-11 pages = extension = .txt mime = text/plain words = 2265 sentences = 154 flesch = 52 summary = title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. Inspired by the previous studies, several covalent inhibitors were experimentally identified to inhibit the 3CL pro activity and viral replication of SARS-CoV-2, and some of the complex crystal structures were solved [14, 15] . baicalensis inhibits SARS-CoV-2 3CL pro activity and the most active ingredient baicalein exhibits an IC50 of 0.39 M. We also identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL pro activity at microM concentration. baicalensis and tested its inhibitory activity against SARS-CoV-2 3CL pro . baicalensis extract at different concentrations on SARS-CoV-2 3CL pro activity were 6 shown in Figure 1A . cache = ./cache/cord-277253-vy0mvzeb.txt txt = ./txt/cord-277253-vy0mvzeb.txt === reduce.pl bib === id = cord-278370-fuu20ae7 author = Palao, M. title = Multiple Sclerosis following SARS-CoV-2 infection date = 2020-07-07 pages = extension = .txt mime = text/plain words = 1544 sentences = 93 flesch = 44 summary = However, available information about demyelinating complications of the central nervous system (CNS) is limited with only one report of acute disseminated encephalomyelitis (ADEM) in a severe COVID-19 patient being published to date 5 and a single case of meningo-encephalitis 6 , the latter with the presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) confirmed by PCR. As viral infections have been linked to the development of demyelinating diseases 7 it would be interesting to know if this relationship also exists in the case of SARS-CoV-2. We present a case of first presentation of demyelinating disease in the form of optic neuritis following SARS-CoV-2 infection. In our case, the patient presented symptoms attributed to COVID-19 infection (anosmia and dysgeusia) prior to the visual manifestations. In this case, SARS-CoV-2 may have acted as a precipitating factor rather than multiple sclerosis being a direct consequence of the infection. cache = ./cache/cord-278370-fuu20ae7.txt txt = ./txt/cord-278370-fuu20ae7.txt === reduce.pl bib === id = cord-277399-0w8is9xm author = Esteves, Sandro C. title = SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services date = 2020-05-22 pages = extension = .txt mime = text/plain words = 4160 sentences = 216 flesch = 38 summary = The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation—as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto‐immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. Sperm banking should be considered in men with HH who respond to therapy, that is, have viable spermatozoa in the ejaculate, in particular, when the continuation of gonadotropin therapy during the SARS-CoV-2 pandemic is neither possible (eg, due to economic or logistic reasons), nor desired. We propose remedies to mitigate the consequences of a prolonged cessation of andrological services due to the SARS-CoV-2 pandemic to vulnerable subgroups of male infertility patients. cache = ./cache/cord-277399-0w8is9xm.txt txt = ./txt/cord-277399-0w8is9xm.txt === reduce.pl bib === id = cord-278618-7tu5c7m1 author = Romano-Bertrand, Sara title = Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission? date = 2020-06-12 pages = extension = .txt mime = text/plain words = 1340 sentences = 70 flesch = 45 summary = This is based on previous knowledge [1] and the doctrine that: a patient positive for SARS-CoV-2 is contagious by respiratory secretions (>10μm in size) that disseminate only on short distance (<1m); SARS-CoV-2 carried on large droplets settles onto local surfaces and is not stable in the air; SARS-CoV-2 aerosol dispersion is possible during AGPs which extensively expose HCWs and therefore HCWs need to wear a respirator for a higher respiratory protection during AGPs. However, an experimental study of van Doremalen et al, [2] assessed the sustainability of SARS-CoV-2 in aerosols (<5μm at 65% of hygrometry (expressed in %RH for relative humidity)) performed using a high-powered machine that does not reflect normal cough conditions (https://www.who.int/publications-detail/modes-of-transmission-of-virus-causing-covid-19-implicationsfor-ipc-precaution-recommendations). They showed that SARS-CoV-2 remained viable and infective at least 3 hours in aerosols, which opened the debate on SARS-CoV-2 transmission through longdistance aerosols (>1m), and questioned the appropriateness of respiratory protection for HCWs. An individual who is well, emits 10 to 10 4 particles per liter of expired air, including 95% of <1μm-size particles [3] . cache = ./cache/cord-278618-7tu5c7m1.txt txt = ./txt/cord-278618-7tu5c7m1.txt === reduce.pl bib === id = cord-280068-rszu1c48 author = Twomey, Julianne D. title = COVID-19 update: The race to therapeutic development date = 2020-10-24 pages = extension = .txt mime = text/plain words = 6195 sentences = 331 flesch = 42 summary = We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-COV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-COV-2, such as REGN-COV2 (an antibody cocktail) and LY-COV555, as well as recombinant human soluble ACE2 protein to counteract SARS-COV-2 binding to the transmembrane ACE2 receptor in target cells. The current review highlights the potential therapeutic strategies for the treatment of COVID-19, including small molecule drugs and therapeutic proteins to target the SARS-CoV-2 viral entry, viral amplification or the host immune responses. cache = ./cache/cord-280068-rszu1c48.txt txt = ./txt/cord-280068-rszu1c48.txt === reduce.pl bib === id = cord-281529-2rec51xg author = Haagmans, Bart L title = Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation date = 2013-12-17 pages = extension = .txt mime = text/plain words = 4032 sentences = 205 flesch = 57 summary = We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. 13 Both MERS-CoV spike protein binding antibodies and virus neutralising antibodies were reported in dromedary camels from diff erent regions, including Oman and Egypt, but no virus shedding could be detected and, therefore, the signifi cance of these observations remained an issue of debate. The camel MERS-CoV clustered with viral sequences obtained from the two human cases related to the farm and with a sequence from Hafr-Al-Batin as the next closest relative (fi gure 1). However, virological testing was unable to detect MERS-CoV viral sequences in camels, probably because only faecal and serum samples were analysed. Our report describes the fi rst detection of MERS-CoV in dromedary camels on a farm in Qatar that had been linked to human cases of the disease. cache = ./cache/cord-281529-2rec51xg.txt txt = ./txt/cord-281529-2rec51xg.txt === reduce.pl bib === === reduce.pl bib === id = cord-277076-yvsyo4l9 author = Berger, A. title = SARS date = 2019-09-12 pages = extension = .txt mime = text/plain words = 4349 sentences = 215 flesch = 45 summary = Measures including source isolation of patientswho only became infectious after onset of clinical symptomsstrict infection control in health care facilities, timely identification and quarantining of exposed contacts, and perhaps also measures to increase social distance, such as travel warnings and screening of travelers, had led to this remarkable and remarkably rapid success. A further, small SARS outbreak occurred again in Guangdong in late 2003/early 2004; molecular analysis of virus isolates from human cases and animals sampled at the same place and time confirmed that this was zoonotically acquired from Paguma larvata. The laboratory diagnosis of SARS remains a challenge; in fact, despite the rapid identification of SARS-CoV as the etiological agent, testing contributed little to the successful control of the 2003 outbreak. A negative antibody test result later than 21 days after the onset of illness is likely to indicate that no infection with SARS-CoV has taken place. cache = ./cache/cord-277076-yvsyo4l9.txt txt = ./txt/cord-277076-yvsyo4l9.txt === reduce.pl bib === id = cord-282142-76jr4p7n author = Wang, Yun title = Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS date = 2020-08-07 pages = extension = .txt mime = text/plain words = 5495 sentences = 292 flesch = 47 summary = Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. Therefore, the effect of SARS-CoV-2 infection on maternal and infant outcomes needs to be explored, especially the intrauterine vertical transmission potential of COVID-19. SARS-CoV infection during pregnancy was associated with a risk of adverse maternal and neonatal complications, including intrauterine growth restriction, preterm delivery, spontaneous miscarriage, severe maternal illnesses, such as, admission to the intensive care unit (ICU), renal failure, and disseminated intravascular coagulopathy, and death (4, 6, 13, (42) (43) (44) (45) (46) . The samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients tested negative for SARS-CoV-2 (5), suggesting no intrauterine vertical transmission of SARS-CoV-2 in the nine pregnant COVID-19 patients. cache = ./cache/cord-282142-76jr4p7n.txt txt = ./txt/cord-282142-76jr4p7n.txt === reduce.pl bib === id = cord-279940-i2rgjpxf author = Comentale, Giuseppe title = Sars-Cov-2 interference in HEME production: is it the time for an early predictive biomarker? date = 2020-06-29 pages = extension = .txt mime = text/plain words = 1348 sentences = 65 flesch = 43 summary = In particular, thrombosis seems to drive the entire disease course: Sars-Cov-2 infection triggers a large thrombophilic response that results in diffuse occlusion of the smaller vessels, especially in the lungs where the result is a wide thrombotic microangiopathy [5] explaining the radiologic "ground glass" pattern. Furthermore, as IL-1 was shown to be a major culprit in the development of many cardiovascular diseases [11] , its involvement in the Sars-Cov-2 infection could explain the high mortality and morbidity rate among cardiopathic patients. Identifying the mechanisms by which Sars-Cov-2 damages the human body, focusing on the structural proteins, could be a possible strategy to finding an effective solution. From this point of view, Sars-Cov-2 seems to be very similar to malaria: many clinical and scientific reports have shown that Covid-19, not only can be successfully treated with chloroquine but also, like malaria, appears to be diagnosed much more frequently in blood group A patients [14] . cache = ./cache/cord-279940-i2rgjpxf.txt txt = ./txt/cord-279940-i2rgjpxf.txt === reduce.pl bib === id = cord-280774-r2xm164s author = Gallizzi, Romina title = Management of pernio‐like cutaneous manifestations in children during the outbreak of covid‐19. date = 2020-09-19 pages = extension = .txt mime = text/plain words = 2083 sentences = 128 flesch = 47 summary = The increased number of cases of pernio-like lesions compared to the cases per year we usually observe, the mild temperatures of those months in Southern Italy and the concomitant lockdown, led us to hypothesize a possible correlation with SARS-CoV-2 infection. This is useful to highlight, as in our case, the D-dimer of our patients was weakly increased, a condition perfectly correlated with the mild symptoms of SARS-CoV-2 putative infection presented. In a report of 19 adolescent patients with a clinical diagnosis of pernio-like lesions nasopharyngeal swab and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Why some children who come into contact with the SARS-CoV-2 do not develop striking respiratory symptoms but present pernio-like lesions with negativity on diagnostic tests? This pathogenic mechanism could explain the appearance of pernio-like lesions due to SARS-CoV-2 infection. In conclusion, we think there is a correlation between pernio-like lesions and SARS-CoV-2 infection, but further studies are needed to prove it. cache = ./cache/cord-280774-r2xm164s.txt txt = ./txt/cord-280774-r2xm164s.txt === reduce.pl bib === id = cord-282338-u01qv3uc author = Cherry, James. D. title = The chronology of the 2002–2003 SARS mini pandemic date = 2004-11-05 pages = extension = .txt mime = text/plain words = 3528 sentences = 176 flesch = 55 summary = SARS-CoV disease should be considered at a minimum in the differential diagnoses for persons requiring hospitalisation for pneumonia confirmed radiographically or acute respiratory distress syndrome without identifiable aetiology and who have one of the following risk factors in the 10 days before the onset of illness: (1) Travel to mainland China, Hong Kong, or Taiwan, or close contact with an ill person with a history of recent travel to one of these areas, or; (2) Employment in an occupation associated with a risk for SARS-CoV exposure (e.g. healthcare worker with direct patient contact or worker in a laboratory that contains live SARS-CoV) or; (3) Part of a cluster of cases of atypical pneumonia without an alternative diagnosis. cache = ./cache/cord-282338-u01qv3uc.txt txt = ./txt/cord-282338-u01qv3uc.txt === reduce.pl bib === id = cord-283956-zgrtux7i author = Amin, Sk. Abdul title = Fight against novel coronavirus: A perspective of medicinal chemists date = 2020-06-12 pages = extension = .txt mime = text/plain words = 5095 sentences = 356 flesch = 52 summary = Like other RNA viruses, the functional significance of this Mpro or chymotrypsin-like protease (3CLpro) of SARS-CoV-2 emerges as an attractive drug target for the development of anti-viral agents. A group of scientists from the Cairo University, Egypt predicted COVID-19 spike binding site to a cell-surface receptor namely Glucose Regulated Protein 78 (GRP78) by employing structural bioinformatics in combination with protein-protein docking [55] . An early virtual screening (VS) study of FDA approved drugs (retrieved from Selleckchem Inc.) against the first resolved SARS-CoV-2 Mpro crystal structure (PDB: 6LU7) was performed. In another study, Elfiky [67] reported SARS-CoV-2 RdRp targeted molecular docking study of some anti-polymerase drugs which have been approved for use against various viruses. This study deals with the information currently available on potential targets for therapeutic invention and screening of new compounds or drug repurposing against SARS-CoV-2 (Figure 8 ). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 cache = ./cache/cord-283956-zgrtux7i.txt txt = ./txt/cord-283956-zgrtux7i.txt === reduce.pl bib === id = cord-279105-e2zjxjox author = Lee, Cheryl Yi-Pin title = Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date = 2020-04-24 pages = extension = .txt mime = text/plain words = 3872 sentences = 212 flesch = 44 summary = With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection. cache = ./cache/cord-279105-e2zjxjox.txt txt = ./txt/cord-279105-e2zjxjox.txt === reduce.pl bib === id = cord-283966-eln8ljjj author = Meyer, Benjamin title = Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013 date = 2014-04-17 pages = extension = .txt mime = text/plain words = 4017 sentences = 207 flesch = 49 summary = Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases. Animals from the Arabian Peninsula had high neutralizing serum activities overall and reciprocal antibody titers <320-1,280, which support recent infection with MERS-CoV or a highly related virus. Expanding upon these studies, we used in the present study a recombinant MERS-CoV spike protein immunofluroescence assay (rIFA) augmented by a validated protein microarray (10, 21) , followed by MERS-CoV-specific neutralization assay, to screen 651 dromedary serum samples from the United Arabian Emirates. In the tested panel of camel serum samples, vIFA titers corresponded well to titers determined by rIFA and generally equal to or higher than titers in the rIFA (Table 1) To confirm results from affinity assays with results from a functional test, we determined endpoint virus neutralization titers by using a microneutralization test against MERS-CoV and BCoV. cache = ./cache/cord-283966-eln8ljjj.txt txt = ./txt/cord-283966-eln8ljjj.txt === reduce.pl bib === id = cord-283709-y59h5bw8 author = Chan, Renee W Y title = Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study date = 2014-08-28 pages = extension = .txt mime = text/plain words = 4858 sentences = 225 flesch = 53 summary = We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. INTERPRETATION: The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with the prototype human MERS-CoV EMC strain to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. To assess the infection potential of dromedary camel Middle East respiratory syndrome coronavirus (MERS-CoV) strains for humans, genetic analysis should be complemented with phenotypic characterisation in physiologically relevant invitro cell cultures. cache = ./cache/cord-283709-y59h5bw8.txt txt = ./txt/cord-283709-y59h5bw8.txt === reduce.pl bib === id = cord-281684-m3m4mhye author = Fagre, Anna C. title = A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date = 2020-09-28 pages = extension = .txt mime = text/plain words = 3707 sentences = 212 flesch = 47 summary = title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. However, to date, there has been only a gross histological analysis of the lung pathological changes following infection and the impact of SARS-CoV-2 neutralizing antibody clones on lung immune infiltrates has yet to be fully assessed. Those antibody clones that blocked the interaction of the RBD with ACE2 and bound to native spike protein were then tested for neutralization of SARS-CoV-2 in a cytopathic effect (CPE) assay with Vero E6 cells. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity cache = ./cache/cord-281684-m3m4mhye.txt txt = ./txt/cord-281684-m3m4mhye.txt === reduce.pl bib === id = cord-281679-xmbnpawj author = Meekins, David A. title = Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date = 2020-08-16 pages = extension = .txt mime = text/plain words = 3402 sentences = 191 flesch = 46 summary = In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Cats, hamsters, and ferrets are highly susceptible to SARS-CoV-2 infection, demonstrate varying clinical and pathological disease manifestations, readily transmit the virus to naïve animals, and mount a virusspecific immune response [22] [23] [24] [25] [26] [27] [28] . Pigs are therefore unlikely to play an important role in the COVID-19 pandemic as a virus reservoir or as a pre-clinical animal model to study SARS-CoV-2 pathogenesis or develop novel countermeasures. cache = ./cache/cord-281679-xmbnpawj.txt txt = ./txt/cord-281679-xmbnpawj.txt === reduce.pl bib === id = cord-279255-v861kk0i author = Dhama, Kuldeep title = Coronavirus Disease 2019–COVID-19 date = 2020-06-24 pages = extension = .txt mime = text/plain words = 23862 sentences = 1164 flesch = 44 summary = Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID19) , emerged in late 2019, and it has posed a global health threat, causing an ongoing pandemic in many countries and territories (1) . Health workers worldwide are currently making efforts to control further disease outbreaks caused by the novel CoV (originally named 2019-nCoV), which was first identified in Wuhan City, Hubei Province, China, on 12 December 2019. cache = ./cache/cord-279255-v861kk0i.txt txt = ./txt/cord-279255-v861kk0i.txt === reduce.pl bib === id = cord-284867-p4jgyusp author = Schöler, Lara title = A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date = 2020-10-09 pages = extension = .txt mime = text/plain words = 4328 sentences = 235 flesch = 42 summary = Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. The fact that the infection and the resulting icELISA signal were neutralized by NAbs present in immune sera indicated that the fast and automated icELISA format is applicable for icNTs. Although most SARS-CoV-2 NTs have not been formally validated and certified, classic plaque reduction neutralization tests (PRNT) are currently considered to represent the gold standard for the detection of SARS-CoV-2-specific NAbs. Various commercially available IgM, IgA, and IgG ELISAs have been compared to PRNTs [e.g., (30) ]. Given the excellent signal-to-noise ratio between infected and uninfected cells, the test was applicable to quantify the efficacy of antiviral compounds, here shown for IFNb, and SARS-CoV-2-specific NAbs present in immune sera. cache = ./cache/cord-284867-p4jgyusp.txt txt = ./txt/cord-284867-p4jgyusp.txt === reduce.pl bib === id = cord-287501-7it4kh0e author = Roh, Changhyun title = A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide date = 2012-05-03 pages = extension = .txt mime = text/plain words = 2964 sentences = 153 flesch = 45 summary = We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. 33 In this study, we report a novel approach for the inhibitor screening of SARS-CoV N protein using a quantum dots (QDs)-conjugated oligonucleotide system with wide applicability for facile and sensitive imaging analysis on a biochip. To the best of our knowledge, this is the first report on the inhibition effects of (-)-catechin gallate and (-)-gallocatechin gallate on SARS-CoV N protein using an optical nanoparticle-based RNA oligonucleotide platform. Among the polyphenolic compounds screened, (-)-catechin gallate and (-)-gallocatechin gallate showed high anti-SARS-CoV N protein activity. At a concentration of 0.05 µg mL -1 , (-)-catechin gallate and (-)-gallocatechin gallate showed more than 40% inhibition activity on a QDs-RNA oligonucleotide biochip platform. cache = ./cache/cord-287501-7it4kh0e.txt txt = ./txt/cord-287501-7it4kh0e.txt === reduce.pl bib === id = cord-282058-it0ojdk3 author = Yu, Yuanqiang title = Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review date = 2020-05-15 pages = extension = .txt mime = text/plain words = 7461 sentences = 389 flesch = 50 summary = References for this review were identified through searches of PubMed for articles published from January 1, 2003, to May 1, 2020, by use of the terms "coronavirus, " "neonate, " "children, " "COVID19, " and "SARS-CoV-2." Relevant articles published between 2003 and 2020 were identified through searches in the authors' personal files. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The symptoms of COVID-19 appear to be less severe in infants and children than in adult patients, similar to the SARS-CoV infection (15) (16) (17) . Of the 34 pregnant women who were confirmed with the SARS-CoV-2 infection in multiple hospitals in Wuhan, including one pregnant woman with a negative nucleic acid test result, 30 had a fever and 16 had a cough (54) (55) (56) (57) . cache = ./cache/cord-282058-it0ojdk3.txt txt = ./txt/cord-282058-it0ojdk3.txt === reduce.pl bib === id = cord-280821-kc0ut4oy author = Venturini, Elisabetta title = Treatment of children with COVID-19: position paper of the Italian Society of Pediatric Infectious Disease date = 2020-09-24 pages = extension = .txt mime = text/plain words = 5481 sentences = 315 flesch = 45 summary = The Italian Society of Pediatric Infectious Diseases steering and scientific committee developed a position paper on treatment of children with COVID-19, reviewing the current literature on this topic and providing indications based on the available literature data. Currently, American guidelines on COVID-19 treatment published in May 2020, recommend both in children and adults to use lopinavir/ritonavir only in the context of clinical trials, given the lack of effectiveness reported now in literature [9, 12] . The latest Chinese guidelines on SARS-Cov-2 pneumoniae do not recommend the use of a specific antiviral for the treatment of COVID-19, and nevertheless include lopinavir/ritonavir among the available therapeutic options for hospitalized patients [29] . In May 2020, following an assessment of the emergency use authorization criteria and available scientific evidence, the FDA issued an emergency use authorization allowing for the administration of remdesivir intravenously by health care providers for the treatment of COVID-19 suspected or laboratoryconfirmed in adults and pediatric patients hospitalized with severe disease [34] . cache = ./cache/cord-280821-kc0ut4oy.txt txt = ./txt/cord-280821-kc0ut4oy.txt === reduce.pl bib === id = cord-284498-54j6ys8s author = Ihsanullah, Ihsanullah title = Coronavirus 2 (SARS-CoV-2) in water environments: Current status, challenges and research opportunities date = 2020-10-16 pages = extension = .txt mime = text/plain words = 5702 sentences = 398 flesch = 47 summary = Some of the significant challenges and research opportunities are the development of standard techniques for the detection and quantification of SARS-CoV-2 in the water phase, assessment of favorable environments for its survival and decay in water; and development of effective strategies for elimination of the novel virus from water. Development of effective standard techniques for the detection and quantification of SARS-CoV-2 in water, assessment of the existing water purification technologies and development of novel advanced water treatment systems are major challenges and open research opportunities. Furthermore, careful surveillance of water and wastewater to be used as an early warning tool for such outbreaks in future, understanding the survival and decay mechanism of the novel virus in water and wastewater, analysis of potential pathways of SARS-CoV-2 into water bodies are other potential research opportunities for environmental researchers [40] [41] [42] [43] [44] . cache = ./cache/cord-284498-54j6ys8s.txt txt = ./txt/cord-284498-54j6ys8s.txt === reduce.pl bib === id = cord-284589-j1609xlu author = Sedova, Mayya title = Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence date = 2020-05-29 pages = extension = .txt mime = text/plain words = 1302 sentences = 85 flesch = 55 summary = RESULTS: Coronavirus3D website integrates data on the SARS-CoV-2 virus mutations with information about 3D structures of its proteins, allowing users to visually analyze the mutations in their 3D context. At the same time, with the exception of the spike protein mutations, there are no publicly available resources that provide analysis for all the other structurally characterized regions of the SARS-CoV-2 proteins. For commercial re-use, please contact journals.permissions@oup.com MN908947.3), with information on boundaries of the predicted proteins, currently available SARS-CoV-2 structures and a histogram of the aminoacid mutation frequency. The first of the lower level panels (Figure 1b) provides interactive visualization of the selected structure or model, with an option for coloring the chain according to the mutation frequency. The Coronavirus3D server was designed to provide users with information and tools to carry out their own analysis of how mutations in the SARS-CoV-2 proteins may affect their 3D-structures and their functions. cache = ./cache/cord-284589-j1609xlu.txt txt = ./txt/cord-284589-j1609xlu.txt === reduce.pl bib === id = cord-284068-sbon3aes author = Mok, Chee Keng title = Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date = 2020-06-22 pages = extension = .txt mime = text/plain words = 1798 sentences = 104 flesch = 49 summary = Validation assays to determine changes in infectious virus titres upon treatment was carried out by testing selected hit compounds in dose-dependent assays in Vero E6 to confirm the primary screen observation and also in the human hepatocarcinoma HuH7 cell line as the latter cell line expresses high levels of the ACE2 receptor (10) and supports replication of coronaviruses (11) . While recent data has shown that vitamin D levels are negatively associated with morbidity and mortality of COVID-19 cases (13, 14) , this is the first report of a direct inhibitory effect of calcitriol on SARS-CoV-2. The authors speculated that vitamin D supplementation could protect against SARS-CoV-2 infection and improve patient disease outcomes (16) , and our finding certainly provides credence to this hypothesis. Given the high transmissibility of SARS-CoV-2 globally (23), if these findings can be replicated in clinical trials, calcitriol may certainly prove to be an effective tool in the effort to control the pandemic while waiting for an effective vaccine to be rolled out globally. cache = ./cache/cord-284068-sbon3aes.txt txt = ./txt/cord-284068-sbon3aes.txt === reduce.pl bib === id = cord-285168-qkadqohe author = Delatorre, Edson title = Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries date = 2020-04-23 pages = extension = .txt mime = text/plain words = 2551 sentences = 149 flesch = 55 summary = Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented. In some countries (Italy and Netherlands) community transmission was traced long before (2-4 weeks) the first confirmed SARS-CoV-2 infection case; while in others (Spain, France, United Kingdom, Germany, and Belgium) the onset date roughly coincides with the time of detection of the first imported cases (Figure 1 ). That quite long period of cryptic community transmission (> 4 weeks) in all analyzed countries draws attention to the great challenge of tracking the early global spread of SARS-CoV-2 and supports that control measures should be adopted at least as soon as first imported cases are detected in a new geographic region. cache = ./cache/cord-285168-qkadqohe.txt txt = ./txt/cord-285168-qkadqohe.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-289716-nleql08z author = Tsitsilonis, Ourania E. title = Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report date = 2020-09-21 pages = extension = .txt mime = text/plain words = 3225 sentences = 143 flesch = 44 summary = Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. According to the manufacturer's package insert, Elecsys ® Anti-SARS-CoV-2 exhibits high overall clinical specificity of 99.81% with no cross-reactivity to the common cold coronaviruses; clinical sensitivity, determined by testing a total of 204 samples from 69 symptomatic patients with a PCR-confirmed SARS-CoV-2 infection, is 100% for samples collected ≥14 days after PCR confirmation in this collective; these values were verified in our study by measuring 25 RT-qPCR SARS-CoV-2 positive and 25 negative samples. cache = ./cache/cord-289716-nleql08z.txt txt = ./txt/cord-289716-nleql08z.txt === reduce.pl bib === id = cord-288731-x2cwyvb7 author = Puenpa, Jiratchaya title = Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date = 2020-10-06 pages = extension = .txt mime = text/plain words = 4207 sentences = 275 flesch = 57 summary = In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. In Thailand the Ministry of Public Health reported the first laboratory-confirmed case of SARS-CoV-2 in a 61-year-old Chinese traveller who had arrived from Wuhan on 12 January 2020. Based on the genome sequences available in GIASID, nucleotide variation in four regions of the SARS-CoV-2 genome was used to conduct viral tracking and identify sites of origin of outbreaks in Thailand. One sample in the current study collected in January 2020 was closely related to the SARS-CoV-2 strain circulating in China at that time identified as type L. A new cohort of imported cases identified in May 2020 included a group of migrant workers in the southern part of Thailand 24 with type G2 SARS-CoV-2. cache = ./cache/cord-288731-x2cwyvb7.txt txt = ./txt/cord-288731-x2cwyvb7.txt === reduce.pl bib === id = cord-289588-n61gz7pi author = Samudrala, Pavan Kumar title = Virology, pathogenesis, diagnosis and in-line treatment of COVID-19 date = 2020-07-17 pages = extension = .txt mime = text/plain words = 3898 sentences = 253 flesch = 56 summary = Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. As far as safety is a major concern, 424 Gilead Sciences announced phase III clinical trial of remdesivir to prove its safety and 425 efficacy in COVID-19 infection (Keown, 16 .03.2020). Epidemiology, causes, clinical manifestation and 687 diagnosis, prevention and control of coronavirus disease (COVID-19) during the early 688 outbreak period: a scoping review First known person-to-784 person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 785 the USA Clinical 803 features of patients infected with 2019 novel coronavirus in Wuhan SARS-CoV-2 (COVID-19) Vaccine Development and Production: An 817 Severe acute respiratory 845 syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The 846 epidemic and the challenges Unique epidemiological and clinical features 949 of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control 950 measures cache = ./cache/cord-289588-n61gz7pi.txt txt = ./txt/cord-289588-n61gz7pi.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-289407-8fje16z1 author = Moore, G. title = Detection of SARS-CoV-2 within the healthcare environment: a multicentre study conducted during the first wave of the COVID-19 outbreak in England date = 2020-09-25 pages = extension = .txt mime = text/plain words = 4720 sentences = 328 flesch = 59 summary = Understanding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is spread within the hospital setting is essential if staff are to be adequately protected, effective infection control measures are to be implemented and nosocomial transmission is to be prevented. 6 Air samples taken during tracheostomy procedures, high flow nasal oxygen treatment, non-invasive ventilation and nebulisation have not contained SARS-CoV-2 RNA 7 and HCWs exposed to unrecognised COVID-19 patients undergoing similar high-risk AGPs have not become infected. . https://doi.org/10.1101/2020.09.24.20191411 doi: medRxiv preprint Several studies, utilising a range of air and surface sampling methods, have been carried out to determine the presence and prevalence of SARS-CoV-2 in the healthcare environment. [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] The detection of viral RNA in air samples differs with study with some reporting widespread airborne contamination 14, 18, 21 but many reporting low or non-detectable concentrations 13, 15, 16, 19 even in samples collected 10 cm from the face of positive patients. Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients cache = ./cache/cord-289407-8fje16z1.txt txt = ./txt/cord-289407-8fje16z1.txt === reduce.pl bib === id = cord-290796-x9xqqcj6 author = Stefanelli, P. title = Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento date = 2020-11-13 pages = extension = .txt mime = text/plain words = 3142 sentences = 212 flesch = 55 summary = All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. The duration of protection against infection with common human coronaviruses appears to be rather short 2, 3 , and there are studies showing declines in IgG antibodies against SARS-CoV-2 among both symptomatic and asymptomatic individuals 4, 5 . In order to evaluate the persistence of SARS-CoV-2 antibodies, we repeated a serosurvey in five municipalities of the Autonomous Province (AP) of Trento, Italy, recruiting those individuals who had resulted positive in a large population-based seroprevalence study conducted 4 months before 14 . The analyser automatically calculates SARS-CoV-2 NC IgG antibody concentration expressed as an is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint cache = ./cache/cord-290796-x9xqqcj6.txt txt = ./txt/cord-290796-x9xqqcj6.txt === reduce.pl bib === id = cord-290290-wyx9ib7s author = Sinegubova, Maria V. title = High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date = 2020-11-05 pages = extension = .txt mime = text/plain words = 5978 sentences = 304 flesch = 49 summary = title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. cache = ./cache/cord-290290-wyx9ib7s.txt txt = ./txt/cord-290290-wyx9ib7s.txt === reduce.pl bib === id = cord-289535-srrfr1es author = Tregoning, J. S. title = Vaccines for COVID‐19 date = 2020-10-18 pages = extension = .txt mime = text/plain words = 14329 sentences = 793 flesch = 44 summary = One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial cache = ./cache/cord-289535-srrfr1es.txt txt = ./txt/cord-289535-srrfr1es.txt === reduce.pl bib === id = cord-293688-g6kag5ij author = Nora, Holtmann title = Assessment of SARS-CoV-2 in human semen - a cohort study date = 2020-05-29 pages = extension = .txt mime = text/plain words = 2231 sentences = 146 flesch = 57 summary = OBJECTIVE: To investigate the presence of viral RNA in human semen of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) recovered and positive patients and to evaluate its presence and relevance on semen parameters. SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19 positive males. SARS-CoV-2 RNA could neither be detected in semen samples from recovered nor from acute infected subjects. On another note, it is of interest, that although it was described before in the literature that viral infections have a negative impact on semen parameters like 306 volume, number of spermatozoa and motility we could not detect a negative influence of the SARS-CoV-2 infection in respect of the aforementioned sperm count parameters in recovered subjects with mild symptoms. We found no evidence of SARS-CoV-2 shedding in semen of recovered males or patients with an acute COVID-19 infection after a recovery time of 32,7 days on average. cache = ./cache/cord-293688-g6kag5ij.txt txt = ./txt/cord-293688-g6kag5ij.txt === reduce.pl bib === === reduce.pl bib === id = cord-292025-dr611nse author = Kam, Kai-qian title = Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children date = 2020-06-13 pages = extension = .txt mime = text/plain words = 1648 sentences = 104 flesch = 52 summary = From 23 March 2020 to 3 April 2020, all inpatient pediatric confirmed COVID-19 cases diagnosed via positive SARS-CoV-2 polymerase chain reaction (PCR) from nasopharyngeal swabs using the real-time reverse transcription (rRT)-PCR assay for the E gene were included in this study. In the 9 infected children with detectable SARS-CoV-2 in buccal specimens, the mean difference of Ct values between buccal and nasopharyngeal specimens for all infected patients was 10.7 (range, 6.1-16.1), and this was statistically significant (P < .001). Our findings confirm that SARS-CoV-2 can be detected in buccal specimens of infected children and that the viral load is the highest in the first week of illness or diagnosis. In our study, the average viral loads of buccal SARS-CoV-2 were consistently lower than the respective nasopharyngeal specimens, with substantial differences between the average Ct values. Two COVID-19-infected children had negative buccal specimens despite detectable nasopharyngeal viral load. cache = ./cache/cord-292025-dr611nse.txt txt = ./txt/cord-292025-dr611nse.txt === reduce.pl bib === id = cord-292742-mio4przi author = McAloose, Denise title = From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date = 2020-10-13 pages = extension = .txt mime = text/plain words = 6364 sentences = 309 flesch = 47 summary = KEYWORDS One Health, Panthera leo, Panthera tigris, SARS-CoV-2, in situ hybridization, lion, rRT-PCR, tiger, virus isolation, whole-genome sequencing, zoo, zoonotic infection C oronaviruses are a recognized cause of disease in humans and animals (1) . Subsequent to confirmation of SARS-CoV-2 infection in the animals, an epidemiologic investigation of zoo staff identified 10 zoo keepers and two managers who provided care for and had close (Յ1.8-m) but not direct contact with the tigers or lions between 16 March 2020 (the date on which the zoo was closed to the public due to the pandemic) and 27 March to 3 April 2020 (timeline of disease onset in the animals). Nine complete SARS-CoV-2 genome sequences (from four tigers, three lions, and two keepers) and eight full-length S gene sequences (from seven symptomatic animals and one asymptomatic animal) were generated directly from respiratory and/or fecal samples (Data Sets 3 and 4). cache = ./cache/cord-292742-mio4przi.txt txt = ./txt/cord-292742-mio4przi.txt === reduce.pl bib === id = cord-291523-4dtk1kyh author = Nguyen, Thanh Thi title = Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date = 2020-07-01 pages = extension = .txt mime = text/plain words = 5361 sentences = 313 flesch = 62 summary = Outcomes of a phylogenetic analysis suggest that the virus belongs to the genus Betacoronavirus, sub-genus Sarbecovirus, which includes many bat SARS-like CoVs and SARS CoVs. Another study in [5] confirms this finding by analysing genomes obtained from three adult patients admitted to a hospital in Wuhan on December 27, 2019. With the cut-off parameter C is set equal to 0.7, the hierarchical clustering algorithm separates the reference sequences into 6 clusters in which cluster "5" comprises all examined viruses of the Sarbecovirus sub-genus, including many SARS CoVs, bat SARS-like CoVs and pangolin CoVs (Fig. 7A) . With the results obtained in Fig. 7D (and also in the experiments with the DBSCAN method presented next), we support a hypothesis that bats or pangolins are the probable origin of SARS-CoV-2. In this Appendix, we first present results of the hierarchical clustering method applied to the dataset that combines Set 1 of reference sequences (Table 1 ) with all 334 SARS-CoV-2 sequences (see Fig. 9 ). cache = ./cache/cord-291523-4dtk1kyh.txt txt = ./txt/cord-291523-4dtk1kyh.txt === reduce.pl bib === id = cord-287847-rmhvc5n5 author = Miles, Brett A. title = Tracheostomy during SARS‐CoV‐2 pandemic: Recommendations from the New York Head and Neck Society date = 2020-04-20 pages = extension = .txt mime = text/plain words = 3458 sentences = 166 flesch = 38 summary = Patients with significant medical comorbidities, acute respiratory distress syndrome/severe respiratory failure and a low chance of recovery who are infected with SARS-CoV-2 should be carefully evaluated, and discussions with family members, consultants, institutional ethics committees and the treating team should focus on overall prognosis and goals of care prior to performing tracheostomy as a routine matter of care. Although there are limited data on the current pandemic to fully inform personal protective equipment (PPE) recommendations, performing tracheostomy in an actively infected SARS-CoV-2 patient is certainly a high-risk procedure for health care workers. Techniques to manage the acute airway with endotracheal intubation, video laryngoscope for example, should be utilized if possible to avoid emergent tracheostomy in SARS-CoV-2 patients due to the high risk of unsafe conditions and health care worker contaminations. • When clinically appropriate, delay of tracheostomy procedures is recommended to allow for reduced viral load and to decrease the risk of nosocomial infection to critical health care providers. cache = ./cache/cord-287847-rmhvc5n5.txt txt = ./txt/cord-287847-rmhvc5n5.txt === reduce.pl bib === id = cord-293082-fw7deem8 author = Zhang, Guangzhi title = Animal coronaviruses and SARS‐CoV‐2 date = 2020-08-16 pages = extension = .txt mime = text/plain words = 2068 sentences = 157 flesch = 48 summary = As of April 7, just four months since its first outbreak, more 48 than 3.4 million confirmed cases and 238,000 deaths have been recorded in 215 countries, areas, 49 and territories, and moreover it seems that severe acute respiratory syndrome coronavirus 2 50 (SARS-CoV-2) that causes COVID-19 will probably continue to circulate around the globe 51 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The health 52 authorities and governments of affected countries have paid attention to current pandemic and 53 have taken immediate measures to block COVID-19 transmission, including utilization of personal 54 protective equipment, quarantine, epidemiological investigation, isolation, clinical data analysis 55 and sharing, public health education, maintaining social distance, the creation of diagnostics, 56 therapeutics, and vaccines, etc (Xiao and Torok 2020) . Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain cache = ./cache/cord-293082-fw7deem8.txt txt = ./txt/cord-293082-fw7deem8.txt === reduce.pl bib === id = cord-291397-look6ddt author = Roberto, Palumbo title = Current treatment of COVID-19 in renal patients: hope or hype? date = 2020-09-28 pages = extension = .txt mime = text/plain words = 5827 sentences = 326 flesch = 46 summary = Given the lack of specific therapy about the ongoing SARS-CoV-2 infection, we conducted a brief review to summarize the mechanism of action and the potentially side effects of the treatment currently available, focusing on the effects of the drugs on renal disease at different stages in terms of therapeutic management and survival. A randomized clinical trial, handled by a Chinese group, suggested that in hospitalized adult patients with severe infection, no benefit was observed with lopinavir/ritonavir beyond standard care in terms of time to clinical improvement, reduction of mortality and safety (side effects and discontinuation of treatment) [29, 30] . Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial cache = ./cache/cord-291397-look6ddt.txt txt = ./txt/cord-291397-look6ddt.txt === reduce.pl bib === id = cord-289598-t8upoq9a author = Yoon, Jane C title = COVID-19 Prevalence among People Experiencing Homelessness and Homelessness Service Staff during Early Community Transmission in Atlanta, Georgia, April–May 2020 date = 2020-09-08 pages = extension = .txt mime = text/plain words = 2980 sentences = 197 flesch = 56 summary = BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7–May 6, 2020. Risk of SARS-CoV-2 infection, the virus that causes COVID-19, may be higher among people experiencing homelessness (PEH) because of challenges in preventing respiratory disease transmission in congregate shelter settings. Our finding of decreased prevalence in four shelters during repeat testing is consistent with reports from skilled nursing facilities and correctional facilities, supporting the use of universal (facility-wide) testing for early identification and isolation of those with positive SARS-CoV-2 as a strategy to interrupt transmission in congregate settings [23] [24] [25] . cache = ./cache/cord-289598-t8upoq9a.txt txt = ./txt/cord-289598-t8upoq9a.txt === reduce.pl bib === id = cord-290904-ngvhk0qy author = Zheng, Zhiqiang title = Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date = 2020-07-16 pages = extension = .txt mime = text/plain words = 4471 sentences = 246 flesch = 57 summary = In this study, we aim to verify if the sequence of the immunogen used to generate mAb 1A9, as well as three other mAbs, is conserved in different coronaviruses and if these mAbs bind to the S protein of SARS-CoV-2 expressed in mammalian cell lines. IF analysis performed on transiently transfected COS-7 cells showed binding of the four mAbs to this S protein fragment of SARS-CoV-2 ( Figure 2B ). Utility of monoclonal antibody 1A9 for detection of S protein in a sandwich ELISA format and in SARS-CoV-2 infected cells Based on indirect ELISA data, mAb 1A9 has the strongest binding to S protein when compared with the other three mAbs. Hence, a sandwich ELISA was performed to determine if it can be paired with the human mAb CR3022 which is known to bind to the S1 subunit of SARS-CoV-2. cache = ./cache/cord-290904-ngvhk0qy.txt txt = ./txt/cord-290904-ngvhk0qy.txt === reduce.pl bib === id = cord-292152-gmru83ac author = Makrinioti, Heidi title = Intussusception in two children with SARS-CoV-2 infection in children date = 2020-08-08 pages = extension = .txt mime = text/plain words = 1752 sentences = 109 flesch = 45 summary = This report compares intussusception as likely associated with SARS-CoV-2 infection in infants that presented in Wuhan and London. Based on the data so far, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in children is shown to run a milder course with lower reported mortality rates (1, 2) . However, as the definition of suspected cases does not include presentations with gastrointestinal symptoms only, there is still no clear answer to the question "should we screen for SARS-CoV-2 infection in children who require admission to hospital with gastrointestinal symptoms?". In addition to the fact that most of the presentations of the infection in children are atypical, there is very recent evidence showing that the highest viral shedding is taking place 2 to 3 days before onset of symptoms (https://www.nature.com/articles/s41591-020-0869-5). This brief report describes two cases of intussusception in infants found to be positive with SARS-CoV-2. This report describes two infants with intussusception and SARS-CoV-2 infection. cache = ./cache/cord-292152-gmru83ac.txt txt = ./txt/cord-292152-gmru83ac.txt === reduce.pl bib === id = cord-292256-jp80u828 author = Moriguchi, Takeshi title = A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 date = 2020-04-03 pages = extension = .txt mime = text/plain words = 1742 sentences = 121 flesch = 53 summary = We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. (Wang et al., 2020a,b) A preliminary report warned that SARS-CoV-2 could have neuroinvasive potential because some patients showed neurologic symptoms such as headache, nausea, and vomiting . This brief report describes the first case of the patient, which brought in by the ambulance due to a convulsion accompanied by unconsciousness, was diagnosed with aseptic encephalitis with SARS-CoV-2 RNA in cerebrospinal fluid. This case shows the neuroinvasive potential of the virus and that we cannot exclude SARS-CoV-2 infections even if the RT-PCR test for SARS-CoV-2 using the patient's nasopharyngeal specimen is negative. cache = ./cache/cord-292256-jp80u828.txt txt = ./txt/cord-292256-jp80u828.txt === reduce.pl bib === id = cord-287758-da11ypiy author = Mônica Vitalino de Almeida, Sinara title = COVID-19 therapy: what weapons do we bring into battle? date = 2020-09-10 pages = extension = .txt mime = text/plain words = 17412 sentences = 1034 flesch = 45 summary = The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell. cache = ./cache/cord-287758-da11ypiy.txt txt = ./txt/cord-287758-da11ypiy.txt === reduce.pl bib === id = cord-293691-ewerquin author = Sauerhering, Lucie title = Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice date = 2020-07-02 pages = extension = .txt mime = text/plain words = 3428 sentences = 191 flesch = 43 summary = RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. To address the previously proposed antiviral activity of CsA in clinically relevant cells, we infected the human bronchial epithelial cell line Calu-3 and primary human alveolar epithelial cells (hAEC) with MERS-CoV and analyzed intracellular viral RNA and infectious particle release in presence of DMSO or CsA ( Figure 1 ). Our data demonstrated that silencing of IRF1 but not treatment by control siRNA lead to a significant increase in MERS-CoV released viral particles in CsA-treated cells ( Figure 6A , B). cache = ./cache/cord-293691-ewerquin.txt txt = ./txt/cord-293691-ewerquin.txt === reduce.pl bib === id = cord-291436-cu5o8ipw author = Martínez-Hernández, Fernando title = Assessing the SARS-CoV-2 threat to wildlife: Potential risk to a broad range of mammals date = 2020-10-05 pages = extension = .txt mime = text/plain words = 2947 sentences = 176 flesch = 57 summary = Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect animals, however, the whole range of potential hosts is still unknown. This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) —both recognized as receptors and protease for coronavirus spike protein— and the genetic variation of the viral protein spike in the recognition sites. Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is causing the biggest pandemic 52 of this century, and could potentially infect between 30 to 40% of the world's populations (De 53 Soto et al., 2020) . Due to its high transmission rate and mortality, researches around the world 54 are trying to get some insight about its origin through the analysis of related-virus genes 55 sequences in humans and animals (Lu R et al., 2020) , and looking for Angiotensin-Converting 56 cache = ./cache/cord-291436-cu5o8ipw.txt txt = ./txt/cord-291436-cu5o8ipw.txt === reduce.pl bib === id = cord-286683-mettlmhz author = Ortiz-Prado, Esteban title = Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review date = 2020-05-30 pages = extension = .txt mime = text/plain words = 13299 sentences = 726 flesch = 45 summary = Interestingly, the increased amounts of proinflammatory cytokines in serum associated with pulmonary inflammation and extensive lung damage described both in SARS [59] and MERS diseases [60] were also reported in the early study of 41 patients with COVID-19 in Wuhan [41] . A recently published case report of a patient with mild-to-moderate COVID-19 revealed the presence of an increased activated CD4+ T cells and CD8+ T cells, antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), and anti-SARS-CoV-2 IgM and IgG antibodies, suggesting that both cellular and humoral responses are important in containing the virus and inhibiting severe pathology [82] . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series cache = ./cache/cord-286683-mettlmhz.txt txt = ./txt/cord-286683-mettlmhz.txt === reduce.pl bib === id = cord-293274-ysr1l557 author = Perisé-Barrios, Ana Judith title = Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4140 sentences = 267 flesch = 54 summary = Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. cache = ./cache/cord-293274-ysr1l557.txt txt = ./txt/cord-293274-ysr1l557.txt === reduce.pl bib === id = cord-293578-yu2i0u2h author = Kusadasi, Nuray title = A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy date = 2020-08-10 pages = extension = .txt mime = text/plain words = 3914 sentences = 259 flesch = 38 summary = The potential role of plasma kallikrein in case of SARS-CoV-2 infection may be summarized as (1) the activation of FXII with the end-product thrombin (coagulation system) (2) the generation of bradykinin with subsequent vascular permeability and leakage (kallikrein-kinin system), (3) the activation of the renin-angiotensin system through conversion of renin from pre-renin leading to a pro-inflammatory state through increased angiotensin 1 receptor activation and (4) the activation of C5, in part through activation of C1 via FXII and in part through activation of C3 via plasmin (complement system). 54, 55 Since prekallikrein is seen as a potential regulator in the fibrin clot formation through FXII activation and is involved in the pathogenesis of thrombosis, there might be an important role for controlling the hypercoagulable state of the patients infected with SARS-CoV-2 as a therapeutic target. Taken together, all these mechanisms may contribute to the complex hypercoagulable state of the critically ill patients infected with SARS-CoV-2 having severe hypoxia and ongoing endothelial activation. cache = ./cache/cord-293578-yu2i0u2h.txt txt = ./txt/cord-293578-yu2i0u2h.txt === reduce.pl bib === id = cord-291710-ixun0c8g author = Su, Haixia title = Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date = 2020-04-14 pages = extension = .txt mime = text/plain words = 2572 sentences = 154 flesch = 53 summary = A crystal structure of SARS-CoV-2 3CLpro in complex with baicalein, the first non-covalent, non-peptidomimetic small-molecule inhibitor, was also determined, revealing a unique binding mode of this natural product with the protease. To validate the binding of baicalin and baicalein with SARS-CoV-2 3CLpro and exclude the suspicion of being the pan-assay interference compounds (PAINS) (15) , their binding affinities with the protease were measured by isothermal titration calorimetry (ITC), widely known as an invaluable tool used to determine thermodynamic parameters of protein-ligand interactions such as Kd (Fig. 1, A and B ; Table 1 ). Moreover, the ITC profiles in combination with their chemical structures suggest that baicalin and baicalein act as noncovalent inhibitors of SARS-CoV-2 3CLpro with a high ligand binding efficiency. The mode of action of baicalein and the structural determinants associated with its binding with SARS-CoV-2 3CLpro were further explored using X-ray protein crystallography. cache = ./cache/cord-291710-ixun0c8g.txt txt = ./txt/cord-291710-ixun0c8g.txt === reduce.pl bib === id = cord-291916-5yqc3zcx author = Hozhabri, Hossein title = The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting date = 2020-08-05 pages = extension = .txt mime = text/plain words = 16737 sentences = 847 flesch = 45 summary = cache = ./cache/cord-291916-5yqc3zcx.txt txt = ./txt/cord-291916-5yqc3zcx.txt === reduce.pl bib === id = cord-293056-kz3w0nfh author = Indes, Jeffrey E. title = Early Experience with Arterial Thromboembolic Complications in Patents with COVID-19 date = 2020-08-28 pages = extension = .txt mime = text/plain words = 1933 sentences = 125 flesch = 51 summary = A retrospective case-control study design was used to identify, characterize and evaluate potential risk factors for arterial thromboembolic disease in SARS-CoV-2 positive patients. Although not statistically significant, in patients with arterial thromboembolism, patients who were SARS-CoV-2 positive compared to those testing negative or not tested tended to be male (66.7 % v. Treatment of arterial thromboembolic disease in the COVID-19 positive patients included open thromboembolectomy in 6 patients (40%), anticoagulation alone in 4 (26.7%) and 5 (33.3%) did not require or their overall illness severity precluded additional treatment. The SARS-CoV-2 positive group included patients with a range of COVID-19 16 symptomatology (mild to severe) as well as those tested as part of routine preoperative 17 preparation. Patients with arterial thrombosis who were SARS-CoV-10 2 positive had significantly higher D-dimer levels, BMI, were younger, and less often on 11 antiplatelet medications as compared to patients who were SARS-CoV-2 negative or not tested. cache = ./cache/cord-293056-kz3w0nfh.txt txt = ./txt/cord-293056-kz3w0nfh.txt === reduce.pl bib === id = cord-296237-i9cti2ok author = Díez, José-María title = Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date = 2020-06-19 pages = extension = .txt mime = text/plain words = 3741 sentences = 220 flesch = 51 summary = Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ). cache = ./cache/cord-296237-i9cti2ok.txt txt = ./txt/cord-296237-i9cti2ok.txt === reduce.pl bib === id = cord-294069-7zr77r71 author = Hu, Xiaowen title = The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients date = 2020-09-30 pages = extension = .txt mime = text/plain words = 2527 sentences = 136 flesch = 50 summary = In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. In addition, we synchronously sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the SARS-CoV-2 distribution on the environmental surfaces during the incubation period of COVID-19 patients. Then, medical staffs stayed in hotel immediately sampled their nasopharyngeal swabs and environmental surfaces, and transferred them to the hospital for further diagnosis Additionally, the frequency of washing behaviors of patients at the quarantine room, including face washing, hands washing, tooth brushing, bathing and excrement, were shown in Table 2 . Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient cache = ./cache/cord-294069-7zr77r71.txt txt = ./txt/cord-294069-7zr77r71.txt === reduce.pl bib === id = cord-293988-f5gvwjyh author = Musso, Nicolò title = New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab date = 2020-09-11 pages = extension = .txt mime = text/plain words = 3223 sentences = 186 flesch = 54 summary = The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. In this study, a domestic cat with clear clinical signs of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. The World Health Organization (WHO) declared COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a worldwide pandemic [1] . As the cat's pathology evolved rapidly and harmfully (the animal died in as little as three days), with clinical signs and rate of disease progression similar to human COVID-19 patients, and because previously published papers reported different cases of feline infection [10, [13] [14] [15] [16] , a nasal swab was collected in order to verify a possible infection with SARS-CoV-2. cache = ./cache/cord-293988-f5gvwjyh.txt txt = ./txt/cord-293988-f5gvwjyh.txt === reduce.pl bib === id = cord-293890-thfros7x author = Carbo, Ellen C. title = Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness date = 2020-08-21 pages = extension = .txt mime = text/plain words = 2315 sentences = 129 flesch = 49 summary = METHODS: The performance of a viral metagenomic protocol in a clinical setting for the identification of novel coronaviruses was tested using clinical samples containing SARS-CoV-2, SARS-CoV, and MERS-CoV, in combination with databases generated to contain only viruses of before the discovery dates of these coronaviruses, to mimic virus discovery. Additionally, the efficacy of detection of novel coronaviruses using capture probes targeting vertebrate viruses [10] [11] known before the current pandemic was analyzed using a SARS-CoV-2 clinical sample. After extraction of human reads, FASTQ files generated for SARS-CoV-2 samples (with and without viral enrichment) were uploaded for classification and de novo assembly by the commercial webbased tool Genome Detective v1.120 (www.genomedetective.com, accessed 2020-05-11) [9] , using a reference database (generated 2019-09-21). In this study, we evaluated the performance of a metagenomic sequencing protocol for the identification of emerging viruses using clinical samples in combination with a simulated reference database. cache = ./cache/cord-293890-thfros7x.txt txt = ./txt/cord-293890-thfros7x.txt === reduce.pl bib === id = cord-296219-zzg9hds0 author = Battaglini, Denise title = Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings date = 2020-08-12 pages = extension = .txt mime = text/plain words = 7486 sentences = 369 flesch = 33 summary = Within this Abbreviations: ACE2, angiotensin-converting enzyme-2; ANE, acute necrotizing encephalopathy; ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; BBB, blood brain-barrier; CA, Ammon's horn; CD, cluster of differentiation; CI, confidence interval; CNS, central nervous system; CoV, coronavirus; COVID-19, coronavirus disease 2019; CT, computed tomography; CXCR, chemokine receptor; DIC, disseminated intravascular coagulation; DO 2 , oxygen delivery; DPP4, dipeptidyl dipeptidase-4; ECMO, extracorporeal membrane oxygenation; FiO 2 fraction of inspired oxygen; FOX, forkhead box; HLH, hemophagocytic lymphohistiocytosis; ICAM, intracellular adhesion molecule; ICH, intracerebral hemorrhage; ICP, intracranial pressure; IFN, interferon; MERS, Middle East respiratory syndrome; MHV, mouse hepatitis virus; MRI, magnetic resonance images; nCoV, novel coronavirus; OR, odds ratio; PaCO 2 , partial pressure of carbon dioxide; PaO 2 partial pressure of oxygen; PbtO 2 brain tissue oxygenation tension; PCR, polymerase chain reaction; PEEP, positive end-expiratory pressure; PRES posterior reversible encephalopathy syndrome; RM, recruitment maneuvers; RNA, ribonucleic acid; SARS, severe acute respiratory syndrome; TLRs, toll-like receptor; TMPRSS2 transmembrane serine protease 2; TNF, tumor necrosis factor; WHO, World Health Organization. cache = ./cache/cord-296219-zzg9hds0.txt txt = ./txt/cord-296219-zzg9hds0.txt === reduce.pl bib === id = cord-296986-8fuj072z author = Kumar, Manish title = A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment date = 2020-05-15 pages = extension = .txt mime = text/plain words = 4465 sentences = 308 flesch = 52 summary = The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): increased transmission beyond China-fourth update cache = ./cache/cord-296986-8fuj072z.txt txt = ./txt/cord-296986-8fuj072z.txt === reduce.pl bib === id = cord-294831-pem059zk author = Zhang, Ling-Pu title = Focus on a 2019-novel coronavirus (SARS-CoV-2) date = 2020-06-11 pages = extension = .txt mime = text/plain words = 6173 sentences = 378 flesch = 54 summary = A report of five patients in a family cluster who traveled to Wuhan and were infected with SARS-CoV-2 was the first report directly illustrating that the virus is capable of person-to-person transmission in hospital and family settings [23] . Xiao and colleagues showed that 53.42% of 73 hospitalized COVID-19 patients had SARS-CoV-2 RNA in stool specimens, and the duration time of positive stool results ranged from 1 to 12 days [27] . In a study published in The Lancet, 41 of 41 patients who were identified as positive for SARS-CoV-2 infection presented with pneumonia and abnormal chest computed tomography (CT) [6] . An article reported in Science shows that SARS-CoV-2 can replicate in the upper respiratory tract of ferrets, indicating that ferrets represent an ideal animal model for evaluating antiviral drugs or vaccine candidates against COVID-19 [64] . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan cache = ./cache/cord-294831-pem059zk.txt txt = ./txt/cord-294831-pem059zk.txt === reduce.pl bib === id = cord-294108-uvnh0s9r author = Dube, Taru title = Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector date = 2020-10-25 pages = extension = .txt mime = text/plain words = 13885 sentences = 845 flesch = 44 summary = [2, [8] [9] [10] This article discusses SARS-CoV-2 nanostructure, the virus biology in connection to its epidemiology, clinical manifestations, and potential and future therapeutic options including repurposed drugs, vaccine/protein therapies, immune therapies, and nanotherapeutics. Mechanisms such as inhibition of viral enzymes (DNA and RNA polymerases, 3CL pro, TMPRSS2, reverse transcriptase, neuraminidase, endonucleases, and other proteases) or processes such as ACE2 cellular receptor inhibitors and endosomal acidification mediators prohibiting viral fusion; molecules interfering with glycosylation of the viral protein, viral assembly, new viral particle transport, and release, and immunomodulation of cytokine release can be potential targets in developing various antiviral drugs for the SARS-CoV-2. [85] A randomized, placebo-controlled, Phase IV clinical trial assessing the safety and efficacy of umifenovir as an adjuvant therapy to the combined therapeutic regimen of IFN 1a, lopinavir/ritonavir and hydroxychloroquine in moderate to severe COVID-19 patients (NCT04350684) is underway. cache = ./cache/cord-294108-uvnh0s9r.txt txt = ./txt/cord-294108-uvnh0s9r.txt === reduce.pl bib === id = cord-293852-r72c6584 author = Greco, S. title = Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era date = 2020-10-31 pages = extension = .txt mime = text/plain words = 8163 sentences = 468 flesch = 40 summary = Different studies found that the values of cardiac Troponins were increased in COVID-19 patients with more severe disease [4, 5, [68] [69] [70] , indicating an association of SARS-CoV-2 with myocardial damage. Moreover, the single-cell RNA-sequencing (scRNAseq) approach has been used to profile the SARS-CoV-2 host-response in the PBMCs of COVID-19 patients, and to comprehensively characterize the immunological changes [124] [125] [126] [127] [128] [129] [130] . However, SARS-CoV-2 infection of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) induced cytotoxic effects and RNA-seq findings highlighted significant transcriptional changes in gene pathways related to cellular metabolism and immune response [131] [132] [133] . This analysis also revealed several host-derived lncRNAs differentially expressed in COVID-19 patient-derived lung tissue, and in SARS-CoV-2 infected epithelial cells, including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and NEAT1 (nuclear-enriched autosomal transcript 1) [151] (Fig. 5) . cache = ./cache/cord-293852-r72c6584.txt txt = ./txt/cord-293852-r72c6584.txt === reduce.pl bib === id = cord-294212-nlekz39f author = Wang, Dongliang title = Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design date = 2020-07-03 pages = extension = .txt mime = text/plain words = 6072 sentences = 305 flesch = 54 summary = Linear B-cell epitopes of the SARS-CoV-2 S protein were predicted by BepiPred 2.0 in IEDB (BepiPred 2.0., Immune Epitope Database and Analysis Resource, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA) with a threshold of 0.55 (corresponding specificity > 0.817 and sensitivity < 0.292), and only the epitopes with more than 8 residues were considered for subsequent antigenicity analysis. Discontinuous B-cell epitopes were predicted via the DiscoTope 2.0 server tool in IEDB with a default threshold of −3.7 (corresponding specificity > 0.75 and sensitivity < 0.47), based on the 3-dimensional (3D) structures of the SARS-CoV-2 S protein (PDB ID: 6VYB, B chain) and the SARS-CoV-2 S protein RBD (PDB ID: 6M0J, B chain). It is worth noting that one epitope ( 786 QILPDPLKPTKRSFIEDLLFNKVTLA 811 ) located in the S2 subunit of the SARS-CoV S protein is an important linear B-cell epitope capable of eliciting the production of a neutralizing antibody (NAb) identified in patients who recovered from SARS-CoV infection (Table S2 ) [13] . cache = ./cache/cord-294212-nlekz39f.txt txt = ./txt/cord-294212-nlekz39f.txt === reduce.pl bib === id = cord-297332-rzf0cw1x author = Wang, Qidi title = Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates date = 2016-04-11 pages = extension = .txt mime = text/plain words = 8688 sentences = 431 flesch = 56 summary = 15 Other observations include evidence of ADE reported here for the first time induced by an inactivated SARS-CoV vaccine in rhesus macaques ( Figure 1 ) and by antisera from SARS patients (Table S1) , as well as ADE in other coronavirus infections. Herein, we discovered that a peptide of the viral sequence simultaneously elicits the antibodies of disparate functions in protection and enhancement against SARS-CoV infection by the studies with host Vero E6 cells in vitro and in non-human primates. In contrast, the immunized monkeys in the Vac3 group had a strongly increased ability to control SARS-CoV infection in association with induction of high levels of anti-S 604−625 antibodies ( Figure 7E ). 44 This study demonstrates for the first time that an antibody (mAb43-3-14) targeting a specific linear epitope (S 597−603 ) of the SARS-CoV spike protein can mediate enhancement of virus infection both in vitro and in non-human primates via an epitope sequence-dependent mechanism. cache = ./cache/cord-297332-rzf0cw1x.txt txt = ./txt/cord-297332-rzf0cw1x.txt === reduce.pl bib === id = cord-296362-9vi8xwu7 author = Wang, Jian-Min title = Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function date = 2008-09-12 pages = extension = .txt mime = text/plain words = 3490 sentences = 199 flesch = 57 summary = title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. For in-depth study of functions of different viral proteins and regulatory sequence elements by reverse genetics, full-length infectious cDNA clones have been established using various techniques including bacterial artificial chromosome (BAC) vector [23] [24] [25] and SARS-CoV replicon cell lines [26] , which can also be used for antiviral drug screening. Construction of a severe acute respiratory syndrome coronavirus infectious cDNA clone and a replicon to study coronavirus RNA synthesis cache = ./cache/cord-296362-9vi8xwu7.txt txt = ./txt/cord-296362-9vi8xwu7.txt === reduce.pl bib === id = cord-296250-7ln7p715 author = Wang, Sheng-Fan title = The pharmacological development of direct acting agents for emerging needed therapy against severe acute respiratory syndrome coronavirus-2 date = 2020-05-20 pages = extension = .txt mime = text/plain words = 4962 sentences = 302 flesch = 43 summary = Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitor. Increasing evidence reveals potential therapeutic agents acting directly against SARS-CoV-2, such as interferon (IFN), RdRp inhibitors, protease inhibitors, coronaviral protease inhibitor, viral entry blocker, neuraminidase inhibitor, vaccine, antibody, agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitors. The novel specific anti-SARS-CoV-2 agents might comprise inhibitors interfering with the viral replication cycle, antibody targeting the host receptor and virus S protein, and inhibitors of host cellular proteases involved in the virus endocytosis pathway. 33, 34 Moreover, evidence showed that diarylheptanoids, the natural products derived from Japanese alder (Alnus japonica), can inhibit the papain-like protease and restore the host innate immunity response against SARS-CoV through maintaining the function of IFNs. 31 Therefore, specific coronaviral proteases might be good candidate targets for developing new drugs to fight COVID-19. cache = ./cache/cord-296250-7ln7p715.txt txt = ./txt/cord-296250-7ln7p715.txt === reduce.pl bib === id = cord-296602-19noki6p author = Law, Helen KW title = Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells date = 2009-06-08 pages = extension = .txt mime = text/plain words = 4427 sentences = 230 flesch = 53 summary = In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. Interestingly, the SARS-CoV infected DCs showed low expression of antiviral cytokines (IFN-α, IFN-β, IFN-γ and IL-12p40), moderate upregulation of proinflammatory cytokines (TNF-α and IL-6) but significant upregulation of inflammatory chemokines (macrophage inflammatory protein (MIP)-1α/CCL3, regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL-5, interferon-inducible protein of 10 kD (IP-10)/CXCL10 and monocyte chemotactic protein (MCP)-1/CCL2. cache = ./cache/cord-296602-19noki6p.txt txt = ./txt/cord-296602-19noki6p.txt === reduce.pl bib === id = cord-294363-bv6xa8v8 author = Zhou, Hong title = Potential Therapeutic Targets and Promising Drugs for Combating SARS‐CoV‐2 date = 2020-05-05 pages = extension = .txt mime = text/plain words = 8902 sentences = 456 flesch = 46 summary = Several studies demonstrated angiotensin converting enzyme 2 (ACE2) as an important therapeutic target of SARS-CoV-2 entry and infection, and many potential targets were subsequently proposed, such as the spike (S) protein and transmembrane serine protease 2 (TMPRSS2). Therefore, accelerating research for potential therapeutic target confirmation, promising drug discovery, and clinical verification development will speed up efforts to combat SARS-CoV-2. In addition to inhibiting the virus directly, ASOs are also expected to target the disease-related proteins involved in the inflammatory cytokine storm process, which could be considered a promising therapeutic strategy for combating SARS-CoV-2 . Although many strategies have been used to block the attachment, entry, replication and release processes to inhibit SARS-CoV-2 infection, how to prevent viral evasion from host immune responses and virus-induced cytopathic effects is considered one of the most urgent problems that need to be solved in SARS-CoV-2-induced pneumonia-associated respiratory syndrome (PARS) patients. cache = ./cache/cord-294363-bv6xa8v8.txt txt = ./txt/cord-294363-bv6xa8v8.txt === reduce.pl bib === id = cord-296268-kb7fgfaq author = Mendonça, Luiza title = SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date = 2020-11-05 pages = extension = .txt mime = text/plain words = 2647 sentences = 161 flesch = 57 summary = Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Understanding the genome 27 replication, assembly and egress of SARS-CoV-2, a multistage process that involves different 28 cellular compartments and the activity of many viral and cellular proteins, is critically Krios to identify each individual infected cell (39.2 % for MOI of 0.1 and 45.4% for MOI 124 0.5) where cryoET tilt series were collected at the cell periphery. The grids were then 125 transferred to a FIB/SEM dualbeam instrument and the same infected cells were subjected to 126 either serial cryoFIB/SEM volume imaging (Zhu et al., 2021) or cryoFIB milling of cellular 127 lamellae where additional cryoET tilt series were collected (Sutton et al., 2020) . cache = ./cache/cord-296268-kb7fgfaq.txt txt = ./txt/cord-296268-kb7fgfaq.txt === reduce.pl bib === id = cord-294912-xl0wzi16 author = Alteri, Claudia title = Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date = 2020-09-08 pages = extension = .txt mime = text/plain words = 3630 sentences = 216 flesch = 49 summary = Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients. In this study, the presence of SARS-CoV-2 genome was evaluated in 55 SARS-CoV-2 rtPCR negative nasopharyngeal swabs from COVID-19 suspected patients thanks to a quantitative ad hoc designed assay based on ddPCR. This proof-of-concept study shows that an in-house ddPCR-based assay can allow an efficient detection of SARS-CoV-2 at low copy number in symptomatic cases resulted negative by standard rtPCR. cache = ./cache/cord-294912-xl0wzi16.txt txt = ./txt/cord-294912-xl0wzi16.txt === reduce.pl bib === id = cord-297599-y4lu8m4k author = Luo, Hua title = Anti-COVID-19 drug screening: Frontier concepts and core technologies date = 2020-10-28 pages = extension = .txt mime = text/plain words = 7665 sentences = 373 flesch = 44 summary = This paper thoroughly summarizes interdisciplinary notions and techniques, including disease model, biochip, network pharmacology, and molecular docking technology, etc., providing a reference for researchers in the screening of drugs for COVID-19 prevention and treatment. Some researchers are currently using mice as an animal model to test drugs and vaccines and to investigate the nature of the infection of SARS-CoV-2 [49] [50] [51] . In fact, in a study led by Qin Chuan on SARS, engineered mice that could express human ACE2 protein was successfully established, leading this Chinese team pioneered the establishment of a SARS-CoV-2 infected hACE2 transgenic mouse model [54] . For example, an effective and convenient novel mouse model in evaluating in vivo protective capacity of the SARS-CoV-2 vaccines was developed through stitching the human gene for ACE2 into an adenovirus by Perlman et al. cache = ./cache/cord-297599-y4lu8m4k.txt txt = ./txt/cord-297599-y4lu8m4k.txt === reduce.pl bib === id = cord-300041-1d9xu4ts author = Chen, Sharon C-A title = Focus on SARS-CoV-2 and COVID-19 date = 2020-10-08 pages = extension = .txt mime = text/plain words = 1024 sentences = 60 flesch = 52 summary = In contrast, more recent pandemics have been dominated by viruses such as influenza H1N1 and H3N2, localised epidemics by Ebola virus, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), MERS-CoV, and now, SARS-CoV-2, the causative agent of COVID-19. However, by having a single edition, with broad focus on human pathology of SARS-CoV-2 infection, we aim to provide the readers of Pathology with insights from different areas of COVID-19 diagnosis. 2 Substantive progress continues to be made in the arena of diagnostic tests for SARS-CoV-2 infection with improvements in molecular diagnostics, rapid antigen detection tests and serological assays. We continue to be faced by the risk of pandemics and we must learn from our observations at present with SARS-CoV-2 infection, and resulting COVID-19 disease. Virus isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for diagnostic and research purposes Rapid deployment of pathology services to a remote Australian quarantine setting during the COVID-19 pandemic cache = ./cache/cord-300041-1d9xu4ts.txt txt = ./txt/cord-300041-1d9xu4ts.txt === reduce.pl bib === id = cord-297842-hkr1wm3k author = Tilley, Kimberly title = A Cross-Sectional Study Examining the Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in a University Student Population date = 2020-10-15 pages = extension = .txt mime = text/plain words = 3894 sentences = 197 flesch = 43 summary = PURPOSE: The aim of the study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university student population. METHODS: This was a cross-sectional survey study based on the World Health Organization population-based seroepidemiological investigational protocol for SARS-CoV-2 conducted between April 29, 2020, and May 8, 2020, examining SARS-CoV-2 antibody prevalence among 790 university students in Los Angeles, CA. With the goal of having the sample distributions match distributions in the population, these strata were selected based on internal university data, indicating that females are more likely to participate in health-related research projects compared with males, and fewer undergraduates (36.4%) spent the end of the Spring 2020 semester in Los Angeles relative to graduate students (76.5%). Seroprevalence of SARS-CoV-2 antibodies in a Los Angeles university student population as of May 8, 2020, was estimated to be 4.0%. cache = ./cache/cord-297842-hkr1wm3k.txt txt = ./txt/cord-297842-hkr1wm3k.txt === reduce.pl bib === id = cord-294136-e69ao8j0 author = Han, Dongsheng title = COVID-19: Insight into the asymptomatic SARS-COV-2 infection and transmission date = 2020-08-27 pages = extension = .txt mime = text/plain words = 5215 sentences = 263 flesch = 42 summary = successfully isolated SARS-CoV-2 from throat swabs of two asymptomatic patients in a cell culture of Caco-2 cells, suggesting the potential for presymptomatic transmission [16] ; (5) Increasing studies show clear epidemiological evidence of human-to-human asymptomatic spread of COVID-19 (described in the following section); (6) Asymptomatic infection tends to be, but is not only, identified among young people (<20 years old) [14, 15, [17] [18] [19] ; And (7) the majority (>90%) of asymptomatic patients appears to have a milder clinical course during hospitalization [15] , but the severity of the symptoms of the secondary patients infected by SARS-COV-2 from asymptomatic patients varies based on their physical constitution [2, 20] . As the transmission of SARS-COV-2 may occur in the early course of infection and a high viral load in respiratory samples could be detected [13] , RT-PCR testing for this virus is more suitable for screening at earlier stages of infection in key populations, such as patients with obvious symptoms and close contacts of asymptomatic patients [35] . cache = ./cache/cord-294136-e69ao8j0.txt txt = ./txt/cord-294136-e69ao8j0.txt === reduce.pl bib === id = cord-296426-upwsdgso author = Virmani, Sarthak title = Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? date = 2020-06-20 pages = extension = .txt mime = text/plain words = 4402 sentences = 222 flesch = 49 summary = While it is true that other non-novel viruses tend to cause more severe disease in immunocompromised patients [1] , no conclusive data is available to suggest an increased susceptibility or severity of SARS-Cov-2 infection in immunosuppressed kidney transplant recipients (KTRs). This was a single center, retrospective chart review performed as a QAPI project to assess similarities in kidney transplant recipients who tested positive for SARS-CoV-2 as compared to those who tested negative, and guide testing recommendations in the setting of limited testing availability during the COVID-19 pandemic. We did not observe any significant association between patient gender, level of education, or history of diabetes on the SARS-CoV-2 test result. Our cohort of KTRs showed no significant difference in ALC between patients who tested positive and negative for SARS-CoV-2 (Table 3 ). Though statistically significant in our small patient cohort, larger studies of KTRs with COVID-19 disease and a history of BKV will be required to confirm and better understand this association. cache = ./cache/cord-296426-upwsdgso.txt txt = ./txt/cord-296426-upwsdgso.txt === reduce.pl bib === id = cord-298669-g2up0cfi author = Pollock, David D title = Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2 date = 2020-07-13 pages = extension = .txt mime = text/plain words = 3261 sentences = 158 flesch = 52 summary = Nevertheless, the evolutionary reasons for low GC content are still debated in even exceptionally well-studied systems with unquestioned animal origins (2020) points out, the mammalian zinc finger antiviral protein (ZAP) binds to CpG dinucleotides in viral RNA genomes and inhibits viral replication and mediates viral degradation (Ficarelli et al., 2020; Ficarelli et al., 2019; Meagher et al., 2019; Takata et al., 2017) . Despite this, Xia (2020) speculated that low viral genomic CpG levels in SARS-CoV-2 required evolutionary time in a previous host species and tissue that more actively selected for CpG depletion than do bats. In addition to being unsupported by positive evidence, Xia's (2020) hypothesis for dogs as intermediate hosts of ancestral viruses giving rise to SARS-CoV-2 requires an unlikely history of cross-species viral transmission (see Fig. 2 for potential hypotheses) for which there is no evidence. cache = ./cache/cord-298669-g2up0cfi.txt txt = ./txt/cord-298669-g2up0cfi.txt === reduce.pl bib === id = cord-298989-qk0k2lmz author = , Umesh title = Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target date = 2020-05-13 pages = extension = .txt mime = text/plain words = 3226 sentences = 179 flesch = 52 summary = title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target Carnosol exhibited highest binding affinity -8.2 Kcal/mol and strong and stable interactions with the amino acid residues present on the active site of SARS-CoV-2 Mpro. Our virtual screening results suggest that these small chemical molecules can be used as potential inhibitors against SARS-CoV-2 Mpro and may have an anti-viral effect on nCoV. SARS-CoV-2 main protease, a potential drug target, crystal structure (PDB-ID: 6Y84) was available and used for docking simulation and identification of potential drug molecule form Indian spices. Details of various kinds of interaction shown between the amino acids near the active site of SARS-CoV-2 main protease along with their respective inhibitor constant (Ki) and biological source and binding energy. Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study cache = ./cache/cord-298989-qk0k2lmz.txt txt = ./txt/cord-298989-qk0k2lmz.txt === reduce.pl bib === id = cord-298850-tgxfki7n author = Figuero-Pérez, Luis title = Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab date = 2020-10-15 pages = extension = .txt mime = text/plain words = 1027 sentences = 84 flesch = 49 summary = title: Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra). We present the case of a 51-year-old patient with bilateral pneumonia secondary to SARS-CoV-2 infection refractory to treatment with tocilizumab who showed improvement after treatment with anakinra. The "cytokine storm" secondary to SARS-CoV-2 infection determines severe COVID-19 disease. 3 The use of anti-IL-6 antibodies in the treatment of SARS-CoV-2 infection is currently under study, being one of the current pillars of COVID-19 disease treatment. cache = ./cache/cord-298850-tgxfki7n.txt txt = ./txt/cord-298850-tgxfki7n.txt === reduce.pl bib === id = cord-297941-7yut9vt4 author = Haq, M. title = Seroprevalence and Risk Factors of SARS CoV-2 in Health Care Workers of Tertiary-Care Hospitals in the Province of Khyber Pakhtunkhwa, Pakistan date = 2020-09-30 pages = extension = .txt mime = text/plain words = 2709 sentences = 210 flesch = 61 summary = In the recent past many studies from the developed countries have been published on the prevalence of SARS CoV2 antibodies and the risk factors of COVID 19 in healthcare-workers but little is known from developing countries. Methods: This cross-sectional study was conducted on prevalence of SARS CoV2 antibody and risk factors for seropositivity in HCWs in tertiary care hospitals of Peshawar city, Khyber Pakhtunkhwa province Pakistan. To our knowledge this is the first study of assessing SARS-CoV-2 antibodies of HCWs form both public and private tertiary care hospitals in Peshawar, Pakistan. To our knowledge this is the first study on prevalence of SARS CoV-2 antibodies in HCW of tertiary care hospitals in Pakistan. The risk of becoming positive for SARS-CoV-2 antibodies did not increase with history of direct contact with COVID patients within or outside the hospital. cache = ./cache/cord-297941-7yut9vt4.txt txt = ./txt/cord-297941-7yut9vt4.txt === reduce.pl bib === id = cord-294527-fct2y5vn author = Guadarrama-Ortiz, Parménides title = Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations date = 2020-09-04 pages = extension = .txt mime = text/plain words = 8820 sentences = 441 flesch = 37 summary = The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this context, SARS-CoV-2 can also cause viral meningitis and encephalitis, as demonstrated by a recent report of a 64-yearold patient with laboratory-confirmed COVID-19 who presented neurologic manifestations during the infection, including lethargy, clonus, and pyramidal signs in the lower limbs as well as stiff neck and Brudzinski sign (76) . Future studies are required to evaluate the serologic features of anti-glycolipid antibodies in patients with COVID-19 to elucidate possible mechanisms underlying the association between SARS-CoV-2 infection and Guillain-Barré syndrome. cache = ./cache/cord-294527-fct2y5vn.txt txt = ./txt/cord-294527-fct2y5vn.txt === reduce.pl bib === id = cord-301693-3hsu2u1k author = He, Yuwen title = Value of Viral Nucleic Acid in Sputum and Feces and Specific IgM/IgG in Serum for the Diagnosis of Coronavirus Disease 2019 date = 2020-08-06 pages = extension = .txt mime = text/plain words = 3551 sentences = 184 flesch = 53 summary = To improve the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we analyzed the results of viral nucleic acid and serum-specific antibody tests on clinical samples from 20 patients with SARS-CoV-2 infection diagnosed at the First Affiliated Hospital of Guangzhou Medical University in China. By comparing various sample types collected from COVID-19 patients, we revealed multiple pathways for SARS-CoV-2 shedding, and a prolonged detectable period for viral nucleic acid test in sputum specimens, demonstrating that the timeline of the viral shedding is of great value in determining the time of release from quarantine or discharge from hospital. We undertook a study on the viral nucleic acids of SARS-CoV-2 in swabs (nasal, pharyngeal), sputum and feces, as well as antibodies in the serum of COVID-19 patients admitted to the First Affiliated Hospital of Guangzhou Medical University, China. cache = ./cache/cord-301693-3hsu2u1k.txt txt = ./txt/cord-301693-3hsu2u1k.txt === reduce.pl bib === id = cord-297132-lhfa9fl5 author = Aghagoli, Ghazal title = Neurological Involvement in COVID-19 and Potential Mechanisms: A Review date = 2020-07-13 pages = extension = .txt mime = text/plain words = 5940 sentences = 280 flesch = 36 summary = In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. The novel 2019 coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) results in a variety of symptoms including fever, cough, and fatigue [1] . The Kawasaki-like syndrome that is now described in young patients following COVID-19 infection and associated with a hyper-inflammatory state is further suggestive of a vascular inflammatory potential of SARS-CoV-2 [48, 49] . Once established in the CNS, SARS-CoV, the virus responsible for Severe Acute Respiratory Syndrome (SARS), has been shown to be capable of inducing rapid transneuronal spread and death of infected neurons in transgenic mice models expressing human ACE2 receptors [63] . cache = ./cache/cord-297132-lhfa9fl5.txt txt = ./txt/cord-297132-lhfa9fl5.txt === reduce.pl bib === id = cord-302584-fwdpzv85 author = Zhu, Ying title = Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates date = 2005-01-01 pages = extension = .txt mime = text/plain words = 3429 sentences = 170 flesch = 54 summary = title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates Despite the fact that the SARS-CoV can cause an atypical and fatal form of pneumonia, the genome structure, gene expression pattern, and protein profiles of the virus are similar to those of other conventional coronaviruses [17] , which are only responsible for mild respiratory tract infections in a wide range of animals including humans, pigs, cows, mice, cats, and birds [10, 19] . In this report, we described the isolation of a new SARS-CoV strain (WHU) from a patient in Hubei Province, China during the late period of SARS outbreak. Comparative study of genetic characterization and nucleotide variation of all known SARS-CoV offers insights into understanding functions of the viral genes and revealing the evolution trends of the virus. cache = ./cache/cord-302584-fwdpzv85.txt txt = ./txt/cord-302584-fwdpzv85.txt === reduce.pl bib === id = cord-300968-dtaasxk1 author = Kliger, Yossef title = From genome to antivirals: SARS as a test tube date = 2005-03-01 pages = extension = .txt mime = text/plain words = 5104 sentences = 272 flesch = 46 summary = Abstract The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. This strategy seems promising in developing anti-viral therapeutic peptides to other viruses that possess type 1 viral fusion proteins [e.g. measles virus and respiratory syncytial virus (RSV)], which share some structural motifs with HIV. Similar to HIV, binding of the viral spike glycoprotein to some receptor(s) on host cells is the first step in SARS-CoV infection. HIV entry involves the binding of the viral envelope glycoproteins (comprising gp120 and gp41, which are the homologous of SARS-CoV S1 and S2, respectively) to CD4 on the host cell plasma membrane. Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoproteinmediated viral entry Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeatderived peptides cache = ./cache/cord-300968-dtaasxk1.txt txt = ./txt/cord-300968-dtaasxk1.txt === reduce.pl bib === id = cord-300399-21xozruq author = Jayamohan, Harikrishnan title = SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations date = 2020-10-18 pages = extension = .txt mime = text/plain words = 13003 sentences = 770 flesch = 44 summary = This review paper examines current molecular diagnostic tools (Fig. 1) , such as amplification-based (including CRISPR-Cas based), antibody and antigen tests, and sequencing, utilized for the detection of SARS-CoV-2. In addition, we also discuss sample preparation aspects that are relevant to wider utilization and point-of-care (POC) deployment of COVID-19 diagnostic tests (PCR, isothermal amplification, and sequencing-including library preparation). RT-PCR broadly involves four steps-lysis of SARS-CoV-2 in the sample, purification of the viral RNA, reverse transcription to complementary DNA (cDNA), and amplification of specific regions of the cDNA, and finally, optical detection of the amplified cDNA. The assay can detect the virus from respiratory swab samples with sensitivity comparable to that of the US Centers for Disease Control and Prevention (CDC) SARS-CoV-2 real-time RT-PCR assay in 30-40 min. Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples cache = ./cache/cord-300399-21xozruq.txt txt = ./txt/cord-300399-21xozruq.txt === reduce.pl bib === id = cord-301974-4wn40ivq author = Berry, Jody D title = Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus date = 2004-09-01 pages = extension = .txt mime = text/plain words = 5877 sentences = 293 flesch = 51 summary = A total of 15 l of SARS-CoV antigen (infected Vero cell lysate) or 5 g of highly purified virus is coated (per spot) for 1 h at 37 • C. c Protein specificity tests shown here were determined by Western immunoblot with purified virus and infected cell lysate under denaturing conditions (Fig. 1) . The four Western immunoblot negative, virus-neutralising mAbs were tested for their ability to bind native SARS-CoV in infected cells by immunofluorescence assay. While purified virus is clearly the optimal antigen tested in this series of experiments, the lower quality SARS-CoV-infected Vero cell lysates are, however, much easier to prepare for diagnostic assays. This paper describes the development of murine mAbs which recognise SARS-CoV antigens in ELISA, immuno-dotblot, Western immunoblot, on the surface of infected cells, and in neutralisation assays. cache = ./cache/cord-301974-4wn40ivq.txt txt = ./txt/cord-301974-4wn40ivq.txt === reduce.pl bib === id = cord-302608-fw4pmaoc author = Huang, Jiao-Mei title = Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date = 2020-03-19 pages = extension = .txt mime = text/plain words = 1890 sentences = 125 flesch = 57 summary = However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human. The S-protein amino acid sequence identity between SARS-CoV-2 and related beta-CoVs showed that bat/Yunnan/RaTG13 shares highest similarity of 97.43%. cache = ./cache/cord-302608-fw4pmaoc.txt txt = ./txt/cord-302608-fw4pmaoc.txt === reduce.pl bib === id = cord-297786-jz1d1m2e author = Hasan, Md. Mahbub title = Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date = 2020-08-26 pages = extension = .txt mime = text/plain words = 3271 sentences = 187 flesch = 54 summary = Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Then, we studied the variants present in different isolates of Bangladesh to investigate the pattern of mutations, identify UMs, and discuss the pseudo-effect of these mutations on the structure and function of encoded proteins, with their role in pathogenicity. To understand the SARS-CoV-2 viral transmission in Bangladesh, we performed phylogenetic analysis on the selected 207 viral genomes reported from different districts of Bangladesh along with selected 467 globally submitted sequences as reported from 42 countries and 6 continents ( Figure 1 ). cache = ./cache/cord-297786-jz1d1m2e.txt txt = ./txt/cord-297786-jz1d1m2e.txt === reduce.pl bib === id = cord-302382-eifh95zm author = Owji, Hajar title = Immunotherapeutic approaches to curtail COVID-19 date = 2020-08-21 pages = extension = .txt mime = text/plain words = 11312 sentences = 606 flesch = 40 summary = Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. Nevertheless, the similarity of severe respiratory failure induced by SARS-CoV-2 to acute respiratory distress syndrome (ARDS) and the deterioration of patients' conditions in around a week following the first symptoms implicate the role of immunity dysregulation in COVID-19 profile [6] . Subsequently, plasma transfusion was recommended as a safe and effective way for the prevention or treatment of the Ebola virus in 2014 and also several other severe viral infections, including MERS, SARS-CoV, and avian influenza A [35, 36] . CP extracted from the SARS-COV-2 survivors may be a promising approach for the protection of COVID-19 patients with antibody deficiency before the development of an effective vaccine [44] . cache = ./cache/cord-302382-eifh95zm.txt txt = ./txt/cord-302382-eifh95zm.txt === reduce.pl bib === id = cord-300716-urmogf97 author = Briguglio, Matteo title = Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes date = 2020-06-05 pages = extension = .txt mime = text/plain words = 9889 sentences = 460 flesch = 42 summary = The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. Keywords: smell, olfactory bulb, coronavirus, SARS-CoV-2, COVID-19, infections, virulence, host pathogen interactions THE SNIFFING OUT OF CORONAVIRUSES Named after their crown-like spikes, coronaviruses are large non-segmented single-stranded positive-sense enveloped RNA viruses that may spill out from animals to infect humans and cause respiratory diseases. It is urgent to discuss whether SARS-CoV-2 can gain access to the central nervous system through a nasal-nervous pathway or other routes and if the fatal respiratory failure may be associated with a neuronal injury in critical brain areas of the host. cache = ./cache/cord-300716-urmogf97.txt txt = ./txt/cord-300716-urmogf97.txt === reduce.pl bib === id = cord-303216-1pbuywz6 author = Das, Gaurav title = Neurological Insights of COVID-19 Pandemic date = 2020-04-22 pages = extension = .txt mime = text/plain words = 2872 sentences = 155 flesch = 54 summary = If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. The intriguing part though is that recently reported studies have noted altered mental health in some COVID-19 patients showing symptoms like anosmia and ageusia thereby indicating a neuroinvasive nature of the virus. The neurological manifestations of SARS-CoV-2 have been recently recognized from CT scan images and MRI scan of the brain of a patient who contracted COVID-19 and showed symptoms of necrotizing hemorrhagic encephalopathy. The brain reportedly, like most other organs, expresses the hACE2 considered to be the entry point of the SARS-CoV-2 viruses in humans and is therefore not immune to viral infection. cache = ./cache/cord-303216-1pbuywz6.txt txt = ./txt/cord-303216-1pbuywz6.txt === reduce.pl bib === id = cord-298067-awo3smgp author = Li, Huanjie title = Transmission Routes Analysis of SARS-CoV-2: A Systematic Review and Case Report date = 2020-07-10 pages = extension = .txt mime = text/plain words = 4853 sentences = 268 flesch = 51 summary = Through associating infection symptoms with the transmission routes of virus and the patient course of the disease, we expect to provide guidelines for clinical diagnosis and the basis for suppressing the spread of the virus and antiviral treatment. On February 1, 2020, respiratory samples of four patients were confirmed SARS-CoV-2 infections by real-time PCR in Jinan Central Hospital, Shandong province, China. Summarizing the published articles, including SARS-CoV and SARS-CoV-2, we combined with epidemiological and clinical data to analyze the possible routes of asymptomatic patients with virus infection in order to provide the basis for suppressing the spread of the virus, and antiviral treatment and advice for the protection of medical staff. The study found that the detection of SARS-CoV-2 nucleic acid positive in a few feces of patients with confirmed COVID-19 cases indicated the presence of a live virus. cache = ./cache/cord-298067-awo3smgp.txt txt = ./txt/cord-298067-awo3smgp.txt === reduce.pl bib === id = cord-304263-5kddk5fa author = C., Selvaa Kumar title = Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2 date = 2020-10-08 pages = extension = .txt mime = text/plain words = 3768 sentences = 252 flesch = 56 summary = In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence. Research studies unveiled the interaction between the structural spike 1 (S1) protein of SARS-CoV-2 with the nicotinic acetylcholine receptors (nAChRs) that are likely to intervene with its biological function (20, 21) . Thus, the insilico study performed to unveil the nicotine's urge for binding with the soluble ACE2 with or without SARS-CoV-2 in compliance with its interaction with the known human neuronal alpha4-beta2 nicotine-acetylcholine receptor (nN-AChR). We found the reported structural protein template of ACE2-SARS-CoV-2 complex with the enlisted PDB ID: 6VW1 (24) incomplete with numerous missing amino acid residues. Structural binding characteristics of nicotine with the soluble angiotensinconverting enzyme 2 (sACE2)-SARS-CoV-2 complex in the context of its interaction with the neuronal nicotinic acetylcholine receptor (nN-AChR). cache = ./cache/cord-304263-5kddk5fa.txt txt = ./txt/cord-304263-5kddk5fa.txt === reduce.pl bib === id = cord-305704-grzrkff9 author = Almutairi, Abdulelah title = Dermatological Manifestations in Patients With SARS-CoV-2: A Systematic Review date = 2020-07-28 pages = extension = .txt mime = text/plain words = 2289 sentences = 134 flesch = 46 summary = Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. The following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. The results were then filtered to include only original research studies examining the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. After searching the abstracts and reviewing the eligibility criteria in identified potential abstracts, a total of seven studies [14] [15] [16] [17] [18] [19] [20] were considered as eligible to be included in the present systematic review, covering a total of 555 patients with SARS-CoV-2 who had dermatological symptoms in the form of skin lesions. cache = ./cache/cord-305704-grzrkff9.txt txt = ./txt/cord-305704-grzrkff9.txt === reduce.pl bib === id = cord-304792-8sdxqmkb author = Khan, Md. Abdullah-Al-Kamran title = SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date = 2020-05-08 pages = extension = .txt mime = text/plain words = 2983 sentences = 207 flesch = 48 summary = title: SARS-CoV-2 proteins exploit host's genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. We have utilized KEGG mapper tool (Kanehisa and Sato, 2020) for the mapping of 197 deregulated genes SARS-CoV-2 interacting host proteins in different cellular pathways. cache = ./cache/cord-304792-8sdxqmkb.txt txt = ./txt/cord-304792-8sdxqmkb.txt === reduce.pl bib === id = cord-302707-cap2rgf7 author = Ng, Dianna L. title = SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood date = 2020-09-17 pages = extension = .txt mime = text/plain words = 4364 sentences = 224 flesch = 50 summary = Here, we present data validating the use of the EUA authorized Abbott Architect SARS-CoV-2 IgG test for antibody detection in two populations in March 2020, a hospitalized COVID-19 patient cohort at a tertiary care hospital in San Francisco and a cohort of blood donors from the San Francisco Bay Area. These studies demonstrate that SARS-CoV-2 seroprevalence in the San Francisco Bay Area was very low, suggesting limited circulation of the virus in the community as of early March, and that IgG and IgM titers are predictive of neutralizing activity, with high positive percent agreement. To evaluate assay sensitivity, we assembled a cohort of 38 hospitalized patients and 5 outpatients at University of California, San Francisco (UCSF) Medical Center and the San Francisco Veterans Affairs (SFVA) Health Care System, all of whom received care at adult inpatient units or clinics and were real-time polymerase chain reaction (RT-PCR) positive for SARS-CoV-2 from nasopharyngeal and/or oropharyngeal swab testing ( Fig. 1a and Supplementary Table 1 ). cache = ./cache/cord-302707-cap2rgf7.txt txt = ./txt/cord-302707-cap2rgf7.txt === reduce.pl bib === id = cord-305931-0pgu2gvh author = Janus, Scott E title = COVID19: a case report of thrombus in transit date = 2020-06-17 pages = extension = .txt mime = text/plain words = 1431 sentences = 85 flesch = 43 summary = In view of the fact that the utility of tissue plasminogen activator in this population is not well studied, we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. 4 Although the utility of tissue plasminogen activator (TPA) for thrombus in transit in other clinical settings has previously been reported, 5 the literature regarding cardiovascular events in SARS-CoV-2 remains scarce; we therefore describe the case of a 64-year-old male who presented with Learning points SARS-CoV-2 pneumonia, who was found to have extensive clot in transit on echocardiography and underwent successful lytic therapy. In view of the fact that the utility of TPA in this population is not well studied, 10 we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. cache = ./cache/cord-305931-0pgu2gvh.txt txt = ./txt/cord-305931-0pgu2gvh.txt === reduce.pl bib === id = cord-304073-f3iwclkm author = Mullick, Jhinuk Basu title = Animal Models to Study Emerging Technologies Against SARS-CoV-2 date = 2020-07-27 pages = extension = .txt mime = text/plain words = 5315 sentences = 322 flesch = 50 summary = Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies. Non-human primates, Syrian hamsters, ferrets, cats, and engineered chimeras mimic the human infection more closely and hold strong potential as animal models of SARS-CoV-2 infection and progression of resulting human disease. Overall, the studies show that the Syrian hamster is a useful animal model for SARS-CoV-2 infection especially to study viral replication, shedding, and transmission through the respiratory tract. In all studies, animals developed NAbs. Overall, the rhesus macaque model has been similar in many aspects to the human COVID-19 pathogenesis. cache = ./cache/cord-304073-f3iwclkm.txt txt = ./txt/cord-304073-f3iwclkm.txt === reduce.pl bib === id = cord-303297-fiievwy7 author = Oberemok, Volodymyr V. title = SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship date = 2020-04-30 pages = extension = .txt mime = text/plain words = 4082 sentences = 174 flesch = 49 summary = In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In addition, it seems that the virus is also more likely to affect the heart than any other similar viruses, so although pneumonia is often the main cause of death, cardiologists and infectionists, for example in Russia, are seeing infected patients whose worst symptoms are not respiratory, but cardiac and many people infected with COVID-19 are dying from heart attacks, as a possible complication of SARS-CoV-2 infection. Despite the initial reports stating that most of the laboratory-confirmed infected patients (27 of 41 cases) had links to the Wuhan seafood market where different animals, including bats, snakes, birds, pangolins, and other small mammals are normally traded within the market [6] , it is now obvious that the newly identified coronavirus SARS-CoV-2 is transmitted with enormous efficacy from human to human via respiratory droplets or close contact. cache = ./cache/cord-303297-fiievwy7.txt txt = ./txt/cord-303297-fiievwy7.txt === reduce.pl bib === id = cord-303741-1ou0cy5k author = Stafstrom, Carl E. title = COVID-19: Neurological Considerations in Neonates and Children date = 2020-09-10 pages = extension = .txt mime = text/plain words = 7035 sentences = 369 flesch = 40 summary = An especially apropos case demonstrated maternal viremia, placental infection shown by immunohistochemistry, and high placental viral load with subsequent neonatal viremia, implying transplacental transfer of SARS-CoV-2 from pregnant mother to fetus [24] ; this newborn presented with neurological symptoms as discussed in Section 3. The lack of unequivocal reports of SARS-CoV-2 being recovered from the CSF of individuals affected with presumed neurological involvement nor in brain tissue from the limited number of autopsied cases strengthens the possibility that the virus does not often directly cause the symptoms but rather, that the neurological sequelae are secondary to hypoxia, cytokine involvement, or some other non-direct mechanism (see Section 6). Finally, 4 of 27 children with COVID-19 associated MIS-C developed new neurologic symptoms including encephalopathy, headache, weakness, ataxia, and dysarthria [81] ; two patients had lumbar punctures and CSF was negative for SARS-CoV-2 in both. cache = ./cache/cord-303741-1ou0cy5k.txt txt = ./txt/cord-303741-1ou0cy5k.txt === reduce.pl bib === id = cord-301730-flv5lnv8 author = Pandey, Anamika title = Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak date = 2020-10-15 pages = extension = .txt mime = text/plain words = 7101 sentences = 346 flesch = 50 summary = Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. Medicinal plant extracts have been reported to impede the replication of several viruses including human immunodeficiency virus (HIV), hepatitis B virus (HBV), poxvirus, severe acute respiratory syndrome (SARS) virus, and herpes simplex virus type 2 (HSV-2) (Vermani and Garg, 2002; Kotwal et al., 2005; Huang et al., 2006) . Different researchers are investigating diverse plant forms based on ethnopharmacological data to find effective anti-CoV drugs with novel action mechanisms especially targeting viral replication. Moreover, creating an effective phyto-anti-COVID drug during this pandemic may provide an idea on the duration and the strategy required for the development of potent plant-based therapeutics in case of such random viral outbreaks (Figure 1) . cache = ./cache/cord-301730-flv5lnv8.txt txt = ./txt/cord-301730-flv5lnv8.txt === reduce.pl bib === id = cord-304306-rxjahqwh author = Vlachakis, Dimitrios title = Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date = 2020-10-08 pages = extension = .txt mime = text/plain words = 8517 sentences = 459 flesch = 48 summary = The currently available antiviral option for hospitalized patients is remdesivir, which may inhibit the replication process by targeting the RdRp. Previously proposed treatments for hospitalized patients included hydroxychloroquine, which thought to disrupt virus endocytosis, and lopinavir/ritonavir, which thought to inhibit SARs-CoV-2 main protease (Astuti and Ysrafil, 2020; Magro, 2020) . Silibilin is predicted to have a dual activity against SARS-CoV-2 infection; silibilin can potentially reduce viral replication activity by targeting NSP12 as a remdesivir-like inhibitor, and modulate inflammatory responses by direct inhibition of STAT3 (BoschBarrera et al., 2020) . A recombinant form of the human ACE2 protein was synthesized as a therapeutic treatment for COVID-19, functioning as a decoy for SARS-CoV-2 and essentially preventing the virus from binding to the cell surface ACE2 (Schuster et al., 2010) . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response cache = ./cache/cord-304306-rxjahqwh.txt txt = ./txt/cord-304306-rxjahqwh.txt === reduce.pl bib === id = cord-304479-uxp1kg86 author = Goodarzi, Pedram title = Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments date = 2020-08-08 pages = extension = .txt mime = text/plain words = 8098 sentences = 434 flesch = 41 summary = Finally, recently, a case report study from Japan shows that orally inhaled ciclesonide alleviates the local inflammation in the lung of patients with COVID-19 pneumonia and inhibits the propagation of the virus by antiviral activity [60] . In the same way, a recent case-report study showed that the adoptive transfer therapy of human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) to a Chinese female patient afflicted with acute COVID19 syndromes improved her laboratory tests and CT images [69] . In vitro evidence of activity against SARS-CoV-2 in infected Vero E6 cells reported with high concentrations of the drug [104, 105, 142] FPV significantly improved the latency to relief for pyrexia and cough [99] FPV in patients with COVID-19 led to decrease of viral load and significant improvement in chest imaging compared with the control arm [98] cache = ./cache/cord-304479-uxp1kg86.txt txt = ./txt/cord-304479-uxp1kg86.txt === reduce.pl bib === id = cord-304295-3mpymd8a author = Khan, Muhammad Muzamil title = Emergence of novel coronavirus and progress toward treatment and vaccine date = 2020-06-04 pages = extension = .txt mime = text/plain words = 2935 sentences = 210 flesch = 48 summary = 10 Favipiravir was effectively used against influenza and has the potential to inhibit viral RNA synthesis and a new study also supports its activity against SARS-CoV-2. 15 In another recent study, Gao et al found that chloroquine phosphate reduced the symptoms of pneumonia in SARS-CoV-2 patients and shortening the duration of disease. 67 Different technologies are being utilized to F I G U R E 1 Mechanism of action of HCQ and CQ by blocking binding of virus with ACE-2 receptors and increasing endosomal pH and preventing fusion with the cell develop potential vaccine for SARS-CoV-2 including DNA and mRNAbased nanoparticles. Clinical study for safety and efficacy of favipiravir in the treatment of novel coronavirus pneumonia (COVID-19) In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cache = ./cache/cord-304295-3mpymd8a.txt txt = ./txt/cord-304295-3mpymd8a.txt === reduce.pl bib === id = cord-304418-k9owyolj author = Le Maréchal, M. title = COVID-19 in clinical practice: a narrative synthesis date = 2020-09-29 pages = extension = .txt mime = text/plain words = 6288 sentences = 367 flesch = 49 summary = Plasmatic detection of SARS-CoV-2 has been reported but only with low viral titers, and mainly in clinically severe cases [44] ; bloodstream infectivity has yet to be demonstrated. The first large clinical trial published on LPV/RTV on SARS-CoV-2 compared 99 patients receiving the antiviral vs 100 receiving SoC alone [124] ; there was no difference between the 2 groups regarding the primary end point (time to improvement) (15 vs 16 days, p=0.09). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Severity or Risk of Death in Patients with Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China cache = ./cache/cord-304418-k9owyolj.txt txt = ./txt/cord-304418-k9owyolj.txt === reduce.pl bib === id = cord-305587-xtqvtleb author = Ma, Cuiqing title = From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date = 2020-05-11 pages = extension = .txt mime = text/plain words = 2310 sentences = 122 flesch = 40 summary = Identification and characterization of novel neutralizing epitopes in the 506 receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated 507 SARS-CoV vaccine Intranasal vaccination of recombinant adeno-associated virus 533 encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces 534 strong mucosal immune responses and provides long-term protection against SARS-CoV infection Receptor-binding domain of SARS-CoV spike protein induces highly 556 potent neutralizing antibodies: implication for developing subunit vaccine Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies 613 primarily targeting the receptor binding region Receptor-binding domain of severe acute respiratory syndrome coronavirus 621 spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. Cross-neutralization of human and palm civet severe acute 636 respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein cache = ./cache/cord-305587-xtqvtleb.txt txt = ./txt/cord-305587-xtqvtleb.txt === reduce.pl bib === id = cord-303517-8971aq02 author = Cajamarca-Baron, Jairo title = SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression date = 2020-10-16 pages = extension = .txt mime = text/plain words = 9096 sentences = 459 flesch = 45 summary = 27, 28 Among other comorbidities, chronic kidney disease is associated with in-hospital mortality, as are cancer and cerebrovascular disease, demonstrated through two meta-analyses that included over fifteen thousand patients ( Table 2) ; studies suggest that superficial fungal infections and psoriasis confer vulnerability to COVID-19; a body mass index (BMI) > 40 kg/m2 is an independent risk factor for complications from the infection; and there are discouraging results regarding underlying neurological disease and SARS-CoV-2. It is even possible that such disease-modifying therapies and their immunosuppressive effect may play a protective role during 19-COVID infection by preventing or dampening hyperimmune activity that, in some cases, could lead to clinical deterioration; there is even a report of a patient with primary progressive multiple sclerosis receiving treatment with ocrelizumab and becoming infected with SARS-CoV-2, in the context of lymphopenia and hypogammaglobulinema expected for this type of treatment, without generating major clinical complications, this hypothesis is obviously limited for now only to academic deductions and limited information. cache = ./cache/cord-303517-8971aq02.txt txt = ./txt/cord-303517-8971aq02.txt === reduce.pl bib === id = cord-306581-g3d0lqxp author = Khattab, Mohamed H. title = Early detection of SARS-CoV-2 from staging PET-CT date = 2020-09-29 pages = extension = .txt mime = text/plain words = 1214 sentences = 78 flesch = 45 summary = METHODS: Here, we present a case study of a mildly symptomatic patient with anal cancer diagnosed with SARS-CoV-2 from a staging PET-CT scan. Given the ongoing COVID-19 pandemic, a nasopharyngeal swab with polymerase chain reaction (PCR) was obtained and was confirmed positive for the potentially lethal SARS-CoV-2 viral infection. In geographic regions with a Fig. 1 Screening positron emission tomography fused with computed tomography demonstrating fluorodeoxyglucose-avid multifocal, rounded, peripheral ground-glass nodules, some demonstrating the reversed halo sign, within the right lower, right middle, and left lower lung lobes concerning for an infectious process significant and increasing COVID-19 case burden, routine PCR testing in the absence of clinical or radiologic findings may be indicated in patients undergoing chemoradiation or radiation, and it is our institutional practice to test all patients receiving any chemotherapy or greater than 10 days of radiation. In the setting of asymptomatic or mildly symptomatic patients with confirmed SARS-CoV-2 infection, multidisciplinary discussion with oncology and infectious disease teams is important to ascertain the risks and benefits of delaying cancer therapy. cache = ./cache/cord-306581-g3d0lqxp.txt txt = ./txt/cord-306581-g3d0lqxp.txt === reduce.pl bib === id = cord-308110-cco3aq4n author = Okamoto, Mika title = The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date = 2020-07-30 pages = extension = .txt mime = text/plain words = 2689 sentences = 148 flesch = 51 summary = In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. Since not only the inhibition of viral replication but also the control of excessive immune activation is mandatory to save COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. cache = ./cache/cord-308110-cco3aq4n.txt txt = ./txt/cord-308110-cco3aq4n.txt === reduce.pl bib === id = cord-306373-61snvddh author = Xu, Xiao-Wei title = Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series date = 2020-02-19 pages = extension = .txt mime = text/plain words = 3594 sentences = 204 flesch = 56 summary = OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). Since the outbreak of covid-19, strict precautionary measures have been implemented in Zhejiang province, including the creation of fever clinics that exclusively receive patients with suspected SARS-Cov-2 infection, defined as presenting with a fever or any respiratory symptoms, including dry cough, and especially in those with a history of travel to Wuhan or exposure to infected people within two weeks before the onset of illness since January 2020. The incubation period was defined as the time from exposure to the onset of illness, which was estimated among patients who could provide the exact date of close contact with individuals from Wuhan with confirmed or suspected SARS-Cov-2 infection. cache = ./cache/cord-306373-61snvddh.txt txt = ./txt/cord-306373-61snvddh.txt === reduce.pl bib === id = cord-308342-ycdok8fc author = Shutler, J. title = Risk of SARS-CoV-2 infection from contaminated water systems date = 2020-06-20 pages = extension = .txt mime = text/plain words = 3147 sentences = 196 flesch = 57 summary = Collectively this evidence suggests that SARS-CoV-2 virus can survive 45 within water and the viral loads within untreated sewage effluent are likely high in countries 46 of high infection rates, a portion of which is viable virus, and therefore water contaminated 47 We note that adenoviruses are 122 known to be particularly resilient, and therefore likely to represent an upper estimate, but 123 also that our selected range is consistent with the 10 -3 value used elsewhere for assessing 124 viral risk in water systems (eg 14 ), including one assessment for SARS CoV-2 transmission 125 risk to wastewater workers 18 . Collectively this means that if a drinking water source 156 was to become infected with SARS-CoV-2 the standard virus removal and disinfection 157 approaches of ultraviolet exposure and chlorination may not reduce the virus below 158 detectable limits. cache = ./cache/cord-308342-ycdok8fc.txt txt = ./txt/cord-308342-ycdok8fc.txt === reduce.pl bib === id = cord-306177-5wefp31y author = Iheagwam, Franklyn Nonso title = Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants date = 2020-09-12 pages = extension = .txt mime = text/plain words = 4804 sentences = 251 flesch = 42 summary = e Unites States Food and Drug Administration-(USFDA-) approved drugs [26] , drugbank [27, 28] , traditional Ayurvedic, Chinese and natural medicine [20, [28] [29] [30] [31] , dark chemical matter, and fooDB [25] are some of the ZINC database subsets that have been rigourously screened for molecules to combat SARS-CoV-2 with main protease, RNA-dependent RNA polymerase, and angiotensin-converting enzyme-2 as the major therapeutic targets. Hence, this study analysed a plethora of natural products (NPs) from African medicinal plants with known bioactivities in human as therapeutic candidates targeting and inhibiting SARS-CoV-2 RNA synthesis, replication, structural protein function, and host-specific receptors/enzymes. In the course of drug discovery, structure-based virtual screening is a computational approach utilised to identify promising novel small chemical ligands from curated chemical compound databases with potential activity against drug targets [48] . cache = ./cache/cord-306177-5wefp31y.txt txt = ./txt/cord-306177-5wefp31y.txt === reduce.pl bib === id = cord-305856-xt3zxajf author = Shanmugam, Chandrakumar title = COVID-2019 – A comprehensive pathology insight date = 2020-09-18 pages = extension = .txt mime = text/plain words = 4597 sentences = 325 flesch = 46 summary = Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. The current pandemic of corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2) led to complete lockdown in many countries contributing to major socio-economic crisis and irreparable recession, globally. [22, 31, 32, 33] Similar to SARS CoV, a recent study reported non-O blood group specifically group A had higher infection and death rates due to COVID-19 owing to absence of protective anti-A IgM antibodies. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer The clinical pathology of severe acute respiratory syndrome (SARS): a report from China cache = ./cache/cord-305856-xt3zxajf.txt txt = ./txt/cord-305856-xt3zxajf.txt === reduce.pl bib === id = cord-304617-5ozf18lg author = Al-Khafaji, Khattab title = Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2 date = 2020-05-15 pages = extension = .txt mime = text/plain words = 4367 sentences = 227 flesch = 51 summary = The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The got protein-drug complex structures from covalent docking were submitted to MD simulations (saquinavir, ritonavir, and remdesivir with SARS-CoV-2 Mpro). The effect of drug-protein interactions upon dynamics of biological system is a fundamental in drug discovery thereby we used RMSD to investigate the influence of saquinavir, ritonavir, and remdesivir upon the stability of SARS-CoV-2 Mpro. One of the more noteworthy findings in this study is that MD simulation analysis that saquinavir, ritonavir, and remdesivir can form stable interaction inside the binding site of SARS-CoV-2 Mpro. cache = ./cache/cord-304617-5ozf18lg.txt txt = ./txt/cord-304617-5ozf18lg.txt === reduce.pl bib === id = cord-307701-fujejfwb author = Gaurav, Shubham title = Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date = 2020-06-07 pages = extension = .txt mime = text/plain words = 2069 sentences = 111 flesch = 54 summary = Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the novel human Corona Virus Disease COVID-19, first reported on November 17 th , 2019 in Wuhan, China [12] . In addition to structural and NSPs, SARS-CoV-2 genome also codes for at least two other viroporin candidates (other than the E protein), namely ORF3a and ORF8 [3] . Moreover, the 29-nucleotide deleted SARS CoV-1 strain had a 23-fold less viral replication as compared to its wild type, suggesting that this mutation effectively attenuated the virus. cache = ./cache/cord-307701-fujejfwb.txt txt = ./txt/cord-307701-fujejfwb.txt === reduce.pl bib === id = cord-308857-otsrexqu author = Goel, Saurav title = Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic date = 2020-05-28 pages = extension = .txt mime = text/plain words = 10608 sentences = 526 flesch = 47 summary = This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. However, the coronavirus isolated from pangolins is 99% similar in a specific region of the Spike protein, which corresponds to the 74 amino acids involved in the Angiotensin-Converting Enzyme 2 (ACE 2) receptor binding domain, which allows the virus to enter human cells to infect them as shown in Figure 2 (b). (figures reprinted with permission) Our nasal lining tissue contains a rich number of cell receptors called angiotensinconverting enzyme 2 (ACE2), which are favourable sites for the SARS CoV-2 to attach its spiked protein to, thus paving way for the entrance of the virus inside the body. cache = ./cache/cord-308857-otsrexqu.txt txt = ./txt/cord-308857-otsrexqu.txt === reduce.pl bib === id = cord-308252-qwoo7b1l author = Cardinale, Vincenzo title = Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis date = 2020-09-16 pages = extension = .txt mime = text/plain words = 4596 sentences = 229 flesch = 36 summary = During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Since inflammation seems to upregulate ACE2 expression [17] , it is important to understand whether patients with inflammatory bowel disease (IBD) are more susceptible to Covid-19 and the cytokine release syndrome (CRS) associated with lung injury and fatal outcome [21] . While the risk of SARS-CoV-2 infection in IBD patients depends on several universal risk factors, including social distancing [22] , older age and comorbidities have been associated with a negative outcome in IBD, whereas IBD treatments have not, highlighting that acute IBD flare prevention and inflammation reduction may avoid severe Covid-19 [23] . cache = ./cache/cord-308252-qwoo7b1l.txt txt = ./txt/cord-308252-qwoo7b1l.txt === reduce.pl bib === id = cord-308583-vtmwv8zl author = Du, Qishi title = Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase date = 2005-02-15 pages = extension = .txt mime = text/plain words = 3856 sentences = 225 flesch = 63 summary = In this research we study the cleavage mechanism, the properties of the relevant chemical bonds, and the catalytic interactions between the octapeptides and the SARS CoV M pro using molecular mechanical and quantum chemical simulations to provide useful insights for the chemical modification. The docking calculation between SARS CoV M pro and the octapeptide AVLQSGFR was performed using the molecular although still bound to the active site, the peptide has lost its cleavability after its scissile bond was modified from a hybrid peptide bond to a strong bond. Fig. 5B is the contour map of differential electronic density of the peptide bond Gln-Ser in the octapeptide AVLQSGFR, obtained by subtracting the electron density in the gaseous phase from the electron density in the background [23] of SARS CoV M pro and solvent water molecules. For the peptide inhibitor of proteinase, the chemical modification to cleavable octapeptide should focus on the scissile peptide bond between R 1 and R 1 0 to be cleaved by SARS CoV M pro . cache = ./cache/cord-308583-vtmwv8zl.txt txt = ./txt/cord-308583-vtmwv8zl.txt === reduce.pl bib === id = cord-307860-iqk1yiw4 author = Ionescu, Mihaela Ileana title = An Overview of the Crystallized Structures of the SARS-CoV-2 date = 2020-10-24 pages = extension = .txt mime = text/plain words = 9856 sentences = 668 flesch = 57 summary = Structures retrieved from PDB (August 12, 2020) were analyzed for relevant information on COVID-19 infection, synthesis of new inhibitors, SARS-CoV-2 interaction with host receptors, and the neutralizing antibodies interactions with spike glycoprotein. The first X-ray structure found (PDB ID 6LU7) belongs to the nonstructural protein 5 (3C-like protease) of the SARS-CoV-2 in complex with the Michael acceptor-based inhibitor N3 (PRD_002214). There is a cryo-EM crystal structure of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex (nsp12/nsp8/nsp7) with the antiviral drug remdesivir (PDB ID 7BV2) [37] . Previous studies on the crystal structures of SARS-CoV S glycoprotein mutants neutralized by 80R-specific antibodies have been considered a hope for the immunotherapeutic Fig. 8 The phylogenetic tree (cladogram) of the CoVs Spike (S) sequences of CoVs with different origin. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites cache = ./cache/cord-307860-iqk1yiw4.txt txt = ./txt/cord-307860-iqk1yiw4.txt === reduce.pl bib === id = cord-309289-vm0k7hfx author = Rothan, Hussin A. title = The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date = 2020-04-14 pages = extension = .txt mime = text/plain words = 1463 sentences = 91 flesch = 46 summary = title: The FDAapproved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, antiinflammatory and anti-ROS properties. We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury. cache = ./cache/cord-309289-vm0k7hfx.txt txt = ./txt/cord-309289-vm0k7hfx.txt === reduce.pl bib === id = cord-309074-pys4aa60 author = Huang, Victoria W. title = Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist date = 2020-05-30 pages = extension = .txt mime = text/plain words = 2644 sentences = 154 flesch = 48 summary = OBJECTIVE: In response to the American Academy of Otolaryngology – Head and Neck Surgery's recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. In response to these evolving needs, the American Academy of Otolaryngology -Head and Neck Surgery (AAO-HNS) telemedicine committee has put forth new recommendations to prioritize novel applications of telehealth to help limit coronavirus disease pandemic spread while maintaining quality care 8 . As testing in the U.S. becomes more available in this era of SARS-CoV-2, telemedicine continues to take the main role of "forward triage", evaluating patients with respiratory symptoms before they arrive in hospitals 23 With the AAO-HNS recommending all otolaryngologists to limit patient care activities to time-sensitive, urgent, and emergent medical conditions, elective surgeries have been canceled with many outpatient clinics rescheduling appointments and transitioning to virtual visits 7, 8 . cache = ./cache/cord-309074-pys4aa60.txt txt = ./txt/cord-309074-pys4aa60.txt === reduce.pl bib === id = cord-310807-p5cb6idp author = Kanwar, Anubhav title = Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio date = 2017-03-25 pages = extension = .txt mime = text/plain words = 2944 sentences = 176 flesch = 46 summary = Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. In this study, we report one of the largest case series of CoV-HKU1 infections among adults presenting with respiratory tract illness and describe their clinical characteristics. Clinical data analysis for adults (patients >18 years of age) included the following: age, gender, hospitalization status, length of hospitalization, clinical features, discharge diagnosis, outcome (death or survived), comorbidities (smoking, lung disease), laboratory and radiology results, intensive care unit (ICU) stay, oxygen use and duration, treatment provided, and exposure history. Similar studies describing HKU1 in pediatric and adult patients have also found an association with upper and lower respiratory tract illness [7, 9, 12, 15, 21] . Our study provides needed insight into clinical characteristics and severity associated with CoV-HKU1 infection in adults in the Northeast region of the United States. cache = ./cache/cord-310807-p5cb6idp.txt txt = ./txt/cord-310807-p5cb6idp.txt === reduce.pl bib === id = cord-299093-zp07aqpm author = Harrison, Andrew G. title = Mechanisms of SARS-CoV-2 transmission and pathogenesis date = 2020-10-14 pages = extension = .txt mime = text/plain words = 6389 sentences = 385 flesch = 46 summary = Thus, evasion of IFN signaling by SARS-CoV-2 and impaired IFN production in J o u r n a l P r e -p r o o f human peripheral blood immune cells might contribute to the productive viral replication, transmission, and severe pathogenesis during COVID-19, although further testing is warranted to fully dissect these putative evasion pathways [95] . For instance, Krt18-hACE2 and betaactin-hACE2-transgenic mice rapidly succumb to SARS-CoV-2 infection with lung infiltration of inflammatory immune cells inducing severe pulmonary disease, accompanied by evident thrombosis and anosmia, which partially recapitulate human COVID-19 [114] [115] . Furthermore, upon viral challenge, lymphocytes have expanded in rhesus macaque models around 5 dpi with complementary B-cell responses against SARS-CoV-2 Spike appearing 10-15 dpi in blood samples [125] ; expansion of these adaptive immune compartments was analogous to those observed in COVID-19 patients [37, 125, [132] [133] [134] . cache = ./cache/cord-299093-zp07aqpm.txt txt = ./txt/cord-299093-zp07aqpm.txt === reduce.pl bib === id = cord-309418-dx6e0lri author = Segalés, Joaquim title = Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain date = 2020-10-06 pages = extension = .txt mime = text/plain words = 3135 sentences = 178 flesch = 48 summary = Several models for SARS-CoV-2 infection have been so far developed in animals, including Egyptian fruit bat, ferret, golden Syrian hamster, cat, humanized angiotensin-converting enzyme 2 (ACE2) transgenic mice (hACE2 mice), and some nonhuman primate species (3) (4) (5) (6) (7) (8) . The clinical condition was finally attributed to a feline hypertrophic cardiomyopathy, but the animal was also infected by SARS-CoV-2. The detection of SARS-CoV-2 RNA in several samples of C1, all of them with Ct values over 30 (low viral load), and presence of antibodies (neutralizing and nonneutralizing) in both C1 and C2, indicated both animals suffered from a productive viral infection, probably linked to the exposure of the cats to COVID-19−affected owners. These experimental results, together with the few reports on SARS-CoV-2 detection in domestic cats and wild felids, indicate that felines are susceptible to infection by the novel coronavirus. cache = ./cache/cord-309418-dx6e0lri.txt txt = ./txt/cord-309418-dx6e0lri.txt === reduce.pl bib === id = cord-309147-c3ikb81g author = Nadeem, Muhammad Shahid title = Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) date = 2020-04-22 pages = extension = .txt mime = text/plain words = 4984 sentences = 315 flesch = 51 summary = According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The recent reports have suggested that SARS-CoV-2 is a modified coronavirus of bat origin [22, 32] , which came to humans as a result of zoonotic transmission [33, 34] . The receptor-binding domain (RBD) of pangolin-CoV has only a one amino acid difference with that of SARS-CoV-2; the infected pangolins exhibit pathological symptoms similar to humans suffering from COVID-19, and their blood circulating antibodies can react with the spike protein of SARS-CoV-2 [35, 36] . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges cache = ./cache/cord-309147-c3ikb81g.txt txt = ./txt/cord-309147-c3ikb81g.txt === reduce.pl bib === id = cord-307489-2liu4anc author = Elavia, Nasha title = An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia date = 2020-05-23 pages = extension = .txt mime = text/plain words = 1321 sentences = 72 flesch = 43 summary = title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia Clinical presentation and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies greatly amongst patients, as supported by recent literature. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) presenting with atypical gastrointestinal symptoms in a patient with SARS-CoV-2 infection. This atypical presentation of PE is unique to our case and highlights the significance of a high index of clinical suspicion for SARS-CoV-2 and its associated thrombogenic effect, even in patients with atypical symptoms. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) in a patient with SARS-CoV-2 pneumonia who mainly presented with gastrointestinal symptoms. Our patient however presented mainly with gastrointestinal symptoms, which have been reported with SARS-CoV-2; however, with significant hypoxia in the absence of a respiratory viral syndrome although with a low pretest probability for PE, we decided to further evaluate the patient for hypoxia. cache = ./cache/cord-307489-2liu4anc.txt txt = ./txt/cord-307489-2liu4anc.txt === reduce.pl bib === id = cord-309633-1cd74xdl author = Rogers, Julia H. title = Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study date = 2020-09-15 pages = extension = .txt mime = text/plain words = 4018 sentences = 241 flesch = 53 summary = MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. Surge testing was initiated on 30 March 2020 (and continued through 24 April) in collaboration with Public Health-Seattle & King County's Communicable Disease Epidemiology Team to conduct contact tracing at 6 shelters where cases of SARS-CoV-2 were previously detected ( Figure 2 ). We calculated the test positivity rate of SARS-CoV-2 infection at shelters by dividing the number of positive cases by the total number of participant encounters in the study period. Overall, 2% of participant encounters involved positive SARS-CoV-2 results, with most cases detected through surge testing events. cache = ./cache/cord-309633-1cd74xdl.txt txt = ./txt/cord-309633-1cd74xdl.txt === reduce.pl bib === id = cord-310239-mmvuij3k author = Arentz, Susan title = Clinical significance summary: Preliminary results of a rapid review of zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections date = 2020-08-01 pages = extension = .txt mime = text/plain words = 3941 sentences = 215 flesch = 47 summary = Indirect evidence from systematic reviews have found zinc supplementation is effective for the prevention of acute respiratory infections in young children and zinc lozenges may reduce the duration of the common cold in adults. As of the 9 June 2020, the preliminary findings of a rapid review of zinc for the prevention or treatment Pending any definitive evidence, clinicians might consider assessing the zinc status of people with chronic disease co-morbidities and older adults as part of a SARS-CoV-2 clinical work-up, as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2. The primary objective of this rapid review was to assess the effects of zinc on the incidence, duration and severity of acute upper or lower respiratory tract infections caused by SARS-CoV-2 infection in people of any age and of any zinc status when used as a preventive supplement or as a therapy. cache = ./cache/cord-310239-mmvuij3k.txt txt = ./txt/cord-310239-mmvuij3k.txt === reduce.pl bib === id = cord-310017-c8rd714a author = Popa, Alexandra title = Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date = 2020-07-17 pages = extension = .txt mime = text/plain words = 5572 sentences = 330 flesch = 49 summary = Moreover, we combined our deep viral genome sequencing data with epidemiologically identified chains of transmissions and family clusters together with biomathematical analyses to study genetic bottlenecks and the dynamics of genome evolution of SARS-CoV-2. We assembled SARS-CoV-2 genome sequences, constructed phylogenies and identified low 15 frequency mutations based on high-quality sequencing results with >5 million reads per sample and >80% of mapped viral reads (Fig. S2A-B) . Our pipeline was validated by experimental controls involving sample titration and technical sample replicates ( Fig. S2CTo investigate the link between local outbreaks in Austria and the global pandemic, we 20 performed phylogenetic analysis of 305 SARS-CoV-2 genomes from the Austrian cases (>96% genome coverage, >80% aligned viral reads) and 7,695 global genomes from the GISAID database (Fig. 1B, Table S1 ). 7 Dynamics of low frequency and fixed mutations in clusters Next, we sought to gain insights into the fundamental processes of SARS-CoV-2 infection by integrative analysis of viral genomes. cache = ./cache/cord-310017-c8rd714a.txt txt = ./txt/cord-310017-c8rd714a.txt === reduce.pl bib === id = cord-311762-f6muhf3d author = Chen, Yu Wai title = Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates date = 2020-02-21 pages = extension = .txt mime = text/plain words = 2798 sentences = 183 flesch = 60 summary = title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates Therefore, we are confident to prepare a structural model of the SARS-CoV-2 3CL pro by molecular modelling (Extended data 7 , Figure S1 ), which will be immediately useful for in silico development of targeted treatment. After we submitted the first draft of this study, the crystal structure of SARS-CoV-2 3CL pro was solved and released (PDB ID 6LU7), which confirms that the predicted model is good within experimental errors (Extended data 7 , Figure S2 ). By analogy, these compounds were speculated to act on SARS-CoV 3CL pro specifically, but there is as yet no crystal structure to support that, although docking studies were carried out to propose various binding modes 20-23 . • Tab S2.docx (The results of virtual screening of drugs on the active site of SARS-CoV-2 3CL pro crystal structure). cache = ./cache/cord-311762-f6muhf3d.txt txt = ./txt/cord-311762-f6muhf3d.txt === reduce.pl bib === id = cord-309138-44qpk2vf author = Khanna, Kanika title = Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle date = 2020-10-03 pages = extension = .txt mime = text/plain words = 6385 sentences = 354 flesch = 43 summary = Moreover, AYUSH has recommended certain preventive and medicinal plants for prevention and prophylactic of COVID-19 including warm extracts of Tinospora cordifolia (advised for chronic fever), Andrograhis paniculata (advised for fever and cold), Cydonia oblonga, Zizyphus jujube and Cordia myxa (enhancing antioxidant, immune-modulatory, anti-allergic, smooth muscle relaxant, anti-influenza activity) and Ever since, has been elucidated that, PAK1 tends to cause cancers, viral diseases like HIV, Hepatitis, pappiloma, influenza, ebola, SARS and corona virus along with immune system suppression of hosts, henceforth, propolis would be quintessential in blocking COVID/coronavirus curbed fibrosis in respiratory tract and boosting the immunity of an individual (Maruta, 2014) . Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: A systematic review Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective cache = ./cache/cord-309138-44qpk2vf.txt txt = ./txt/cord-309138-44qpk2vf.txt === reduce.pl bib === id = cord-310507-5h6egve4 author = van Doorn, Amarylle S. title = Systematic review with meta‐analysis: SARS‐CoV‐2 stool testing and the potential for faecal‐oral transmission date = 2020-08-27 pages = extension = .txt mime = text/plain words = 3532 sentences = 238 flesch = 49 summary = Since December 2019, the world has been dealing with the outbreak of the novel Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) leading to Corona Virus Disease 2019 (COVID-19) that emerged in Wuhan, China. However, there is a growing body of studies in which SARS-CoV-2 RNA was detected in stool samples (including anal swabs) from COVID-19 patients. 11, 15, 16 This study aims to (1) critically assess the clinical relevance of testing stool samples and anal swabs and (2) provide a critical overview of the available literature regarding the faecal-oral transmission of SARS-CoV-2. We collected the following data from the eligible original articles: study design, geographic location, study period, number of patients, age, types of tested specimens, number of tested specimens, methods of the performed tests, duration and prevalence of positive test results in different specimens, disease severity, gastrointestinal symptoms, endoscopic results, specific evidence supporting faecal-oral transmission and remarkable patient/population characteristics. cache = ./cache/cord-310507-5h6egve4.txt txt = ./txt/cord-310507-5h6egve4.txt === reduce.pl bib === id = cord-308945-i2agpvhk author = Phipps, William S title = SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity date = 2020-07-15 pages = extension = .txt mime = text/plain words = 3167 sentences = 174 flesch = 50 summary = METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)–based respiratory viral panel. Long et al 8 have described a variable antiviral IgM and IgG immune response to SARS-CoV-2 infection in a Chinese population in which seroconversion in a group of 285 patients from 3 hospitals showed IgG positivity for all cases beyond 17 to 19 days. The goals of this study were to ascertain key performance metrics of analytical specificity and cross-reactivity for a SARS-CoV-2 IgG serologic assay, perform a detailed cross-sectional and serial assessment of IgG and IgM antibody responses in suspected COVID-19 patients, and determine their relation to disease severity. SARS-CoV-2 IgG antibody results agreed with the PCR-negative samples for 96 of 97 (99%) of cases, including 55 instances of patients with new or acute-on-chronic symptoms suspicious for COVID-19 and with known time of onset. cache = ./cache/cord-308945-i2agpvhk.txt txt = ./txt/cord-308945-i2agpvhk.txt === reduce.pl bib === id = cord-309474-9h9w46eq author = Schiaffini, Riccardo title = School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology date = 2020-07-03 pages = extension = .txt mime = text/plain words = 2515 sentences = 118 flesch = 52 summary = We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. This is a real-life, retrospective, observational study aimed at evaluating how constant parental care compared to spending time outside home affected glycemic control in pre-school and school children with T1D utilizing Tandem Basal IQ system before and during the quarantine period due to pandemic COVID-19 infection. Our observational real-life study confirms the positive effect of parental care in T1D very young children and that, though new technologies can potentially improve diabetes outcomes also in this sub-population, maintenance of a good glucose control remains largely dependent on family competence and education 10. cache = ./cache/cord-309474-9h9w46eq.txt txt = ./txt/cord-309474-9h9w46eq.txt === reduce.pl bib === id = cord-310221-car394ou author = Chandrashekar, Abishek title = SARS-CoV-2 infection protects against rechallenge in rhesus macaques date = 2020-05-20 pages = extension = .txt mime = text/plain words = 2540 sentences = 140 flesch = 44 summary = We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. On day 2 following challenge, both necropsied animals demonstrated multifocal regions of inflammation and evidence of viral pneumonia, including expansion of alveolar septae with mononuclear cell infiltrates, consolidation, and edema (Fig. 3, A and B) . SARS-CoV-2 infection in rhesus macaques led to humoral and cellular immune responses (Fig. 2) and provided protection against rechallenge (Fig. 5) . In summary, SARS-CoV-2 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against SARS-CoV-2 rechallenge. cache = ./cache/cord-310221-car394ou.txt txt = ./txt/cord-310221-car394ou.txt === reduce.pl bib === id = cord-311214-eqwxkwqa author = Kumar, Roshan title = Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date = 2020-04-16 pages = extension = .txt mime = text/plain words = 2724 sentences = 184 flesch = 60 summary = Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. A manually annotated reference database was generated using the Genbank 128 file of Severe acute respiratory syndrome coronavirus 2 isolate-SARS-CoV-129 2/SH01/human/2020/CHN (Accession number: MT121215) and open reading frames (ORFs) 130 were predicted against the formatted database using prokka (-gcode 1) [22] . All these isolates 189 were found to harbor 9 open reading frames coding for ORF1a (13218 bp) and ORF1b (7788 190 bp) polyproteins, surface glycoprotein or S-protein (3822 bp), ORF3a protein (828 bp Our analysis revealed that strains of human infecting SARS-CoV-2 are novel and highly 201 identical (>99.9%). In this study, the analysis was 358 performed on the genomes of the novel SARS-CoV-2 isolates recently reported from different 359 countries to understand viral pathogenesis. cache = ./cache/cord-311214-eqwxkwqa.txt txt = ./txt/cord-311214-eqwxkwqa.txt === reduce.pl bib === id = cord-313344-rqvi2ksc author = Farcas, Gabriella A. title = Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus date = 2005-01-15 pages = extension = .txt mime = text/plain words = 2427 sentences = 104 flesch = 46 summary = Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). The purpose of the present study was to investigate the presence of SARS-CoV, the degree of viral dissemination, and the viral loads in multiple organ samples from all patients who died of SARS during the Toronto outbreak (March to September 2003) and underwent a postmortem examination and compare the results with those found in patients who died of other causes during the outbreak. A total of 212 discrete postmortem organ samples, including lung, liver, spleen, kidney, small bowel, large bowel, lymph nodes, heart, and skeletal muscle, were prospectively collected from the 21 patients who died of SARS and underwent autopsies. cache = ./cache/cord-313344-rqvi2ksc.txt txt = ./txt/cord-313344-rqvi2ksc.txt === reduce.pl bib === id = cord-311125-v9ddes3c author = Cooper, Keiland W. title = COVID-19 and the chemical senses: supporting players take center stage date = 2020-07-01 pages = extension = .txt mime = text/plain words = 9480 sentences = 510 flesch = 49 summary = Given data suggesting that ACE2 is necessary for SARS-CoV2 to infect host cells, researchers have used a variety of approaches to discern the pattern of expression of ACE2 and other viral entry proteins across the tissue landscape, with the goal of inferring possible target cells and disease mechanisms. It remains unclear whether SARS-CoV-2 (given that it likely does not directly infect OSNs, and thus cannot pass directly through the olfactory nerve, see However, scSeq and immunostaining of the mouse OB has revealed -as in the nose -that bulb neurons do not express detectable levels of ACE2 ( Figure 2 ) . This model suggests that neural function is altered indirectly due to sequelae of SARS-CoV-2 infection of peripheral support cells, including (but not limited to) local inflammation and changes in OSN gene expression and ciliary structure. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia cache = ./cache/cord-311125-v9ddes3c.txt txt = ./txt/cord-311125-v9ddes3c.txt === reduce.pl bib === id = cord-310624-3kojrkz7 author = Flores-Alanis, Alejandro title = The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789 date = 2020-08-27 pages = extension = .txt mime = text/plain words = 3064 sentences = 181 flesch = 56 summary = In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans. RESULTS: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved. cache = ./cache/cord-310624-3kojrkz7.txt txt = ./txt/cord-310624-3kojrkz7.txt === reduce.pl bib === id = cord-311114-ggcpsjk8 author = Radhakrishnan, Chandni title = Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date = 2020-09-09 pages = extension = .txt mime = text/plain words = 4383 sentences = 274 flesch = 52 summary = The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. In our analysis, we mapped the SARS-CoV-2 genetic variants obtained from Kerala genomes to the 132 primer or probes sequence and calculated the melting temperature (Tm) of the mutant with the wild type sequence. cache = ./cache/cord-311114-ggcpsjk8.txt txt = ./txt/cord-311114-ggcpsjk8.txt === reduce.pl bib === id = cord-312160-2820aftb author = Ibrahim, Mahmoud A.A. title = In silico Drug Discovery of Major Metabolites from Spices as SARS-CoV-2 Main Protease Inhibitors date = 2020-10-08 pages = extension = .txt mime = text/plain words = 2443 sentences = 162 flesch = 51 summary = Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). The binding energies of the investigated spices compounds with SARS-CoV-2 M pro were estimated using molecular mechanical-generalized Born surface area (MM-GBSA) approach with modified GB model (igb=2) implemented in AMBER16 software [27] . The physicochemical parameters of the most promising natural spices as SARS-CoV-2 M pro inhibitors were predicted using the online Molinspiration cheminformatics software %ABS was estimated as follows [28] : The online web-based tools of SwissTargetPredicition (http://www.swisstargetprediction.ch) were applied to predict the biological targets for the most promising natural spices as SARS-CoV-2 M pro inhibitors. Since the main protease of SARS-CoV-2 (M pro ) plays a critical role in the viral replication process, structure-based computational modeling of ligand-receptor interactions and molecular dynamics has been used to screen metabolites from common spices as potential M pro inhibitors. cache = ./cache/cord-312160-2820aftb.txt txt = ./txt/cord-312160-2820aftb.txt === reduce.pl bib === id = cord-312652-zhccmfgw author = Hu, Xiumei title = Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA date = 2020-06-20 pages = extension = .txt mime = text/plain words = 3001 sentences = 176 flesch = 50 summary = According to Chinese Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7), SARS-CoV-2 specific IgM becomes detectable around 3-5 days after onset and IgG reaches a titration of at least 4-fold increase during convalescence compared with the acute [9] . In order to establish a safe and accurate method for detecting SARS-CoV-2 specific antibodies, we retrospectively assessed the impact of sera heat-inactivation at 56℃ for 30 minutes on the levels of SARS-CoV-2 IgM or IgG antibodies. Therefore, our analysis provide evidence that sera inactivated by heating at 56℃ for 30 minutes could reduce the risk of virus contamination, and would not impair the detection efficacy of SARS-CoV-2 IgM or IgG testing using this ELISA assay. In summary, sera inactivated by heating at 56℃ for 30 minutes could minimize the risk of virus contamination and did not impair the positive detection rate using SARS-CoV-2 antibody detection kit (ELISA-immunoassay) and eventually represents a valuable contribution to a safer COVID-19 serological diagnosis. cache = ./cache/cord-312652-zhccmfgw.txt txt = ./txt/cord-312652-zhccmfgw.txt === reduce.pl bib === id = cord-311847-2czqs84q author = Pennisi, Manuela title = SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date = 2020-07-31 pages = extension = .txt mime = text/plain words = 9002 sentences = 433 flesch = 40 summary = Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). Although there are limitations in the epidemiological studies carried on COVID-19, as well as limited case records for determining the actual incidence of these complications, some patients reported neurological symptoms, but clinical findings and pathogenic features have not yet systematically addressed. The aims of this review are i) to summarize the available information on the relationship between CoVs and the nervous system, ii) to identify the potential targets and routes of entry of SARS-CoV-2 into the nervous system, and iii) to describe the range of the neurological features reported to date in patients with COVID-19 and the proposed pathogenic mechanisms. Indeed, no axonal transport of SARS-CoV-2 to the brain has been demonstrated in the hamster model during the first two weeks after infection [89] , and no viral accumulation or persistence has been reported in cerebral olfactory regions of autopsy material from patients with COVID-19 [90] . cache = ./cache/cord-311847-2czqs84q.txt txt = ./txt/cord-311847-2czqs84q.txt === reduce.pl bib === id = cord-309876-l0xginsa author = Vena, Antonio title = Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors date = 2020-08-27 pages = extension = .txt mime = text/plain words = 3065 sentences = 168 flesch = 45 summary = A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59–3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19–6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75–6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94–88.71, p = 0.001). In the present observational study performed on a large sample of subject in northern Italy, we found the following: (1) the overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0%; (2) occupational exposure to the virus, long-term care facility residency, as well as previous symptoms of influenza-like illness or loss of sense of smell or taste were independently associated with anti-SARS-CoV-2 positivity. cache = ./cache/cord-309876-l0xginsa.txt txt = ./txt/cord-309876-l0xginsa.txt === reduce.pl bib === id = cord-313505-2lr4xara author = Resende, Paola Cristina title = Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date = 2020-06-18 pages = extension = .txt mime = text/plain words = 1145 sentences = 99 flesch = 55 summary = title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. Introduction 59 COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 60 (SARS-CoV-2), is leading to high rates of acute respiratory syndrome, hospitalization, and death 61 genomes (> 10% of ambiguous positions), we obtained a final dataset of 7,674 sequences. The prevalence of the sub-clade 211 B.1.1 in our sample (92%) was much higher than that observed in other Brazilian sequences 212 available in GISAID (36%) (Fig. 1C) phylogenetic tree, consistent with the hypothesis of multiple independent introductions (Fig. 2) (Fig. 2) . Revealing COVID-19 Transmission by SARS-CoV-2 Genome 410 Sequencing and Agent Based Modelling. cache = ./cache/cord-313505-2lr4xara.txt txt = ./txt/cord-313505-2lr4xara.txt === reduce.pl bib === id = cord-311848-8n9ee57a author = Giesen, Nicola title = Evidence-based Management of COVID-19 in Cancer Patients – Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) date = 2020-09-21 pages = extension = .txt mime = text/plain words = 7678 sentences = 516 flesch = 48 summary = It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria. We do not 285 recommend to delay/discontinue radiotherapy, targeted therapy, endocrine therapy or surgery in 286 cancer patients without suspected/confirmed SARS-CoV-2 infection (DII u ) as no impact on mortality 287 of such prior treatments was seen in several large cohort studies of 20, 31, 40, 94 288 In patients with COVID-19, it is strongly recommended to delay/discontinue chemotherapy, if 289 possible, as chemotherapy within two weeks of admission was a major risk factor for severe COVID-290 19 in a large Chinese cohort study (AII u ). Clinical characteristics and risk factors 38 associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, 39 retrospective, cohort study cache = ./cache/cord-311848-8n9ee57a.txt txt = ./txt/cord-311848-8n9ee57a.txt === reduce.pl bib === id = cord-312670-hi3fjne4 author = Corman, V. M. title = Coronaviren als Ursache respiratorischer Infektionen date = 2019-08-27 pages = extension = .txt mime = text/plain words = 2307 sentences = 257 flesch = 49 summary = Zusätzlich zu diesen ständig im Menschen zirkulierenden Varianten wurden in den vergangenen Jahren zwei CoV im Menschen gefunden, nämlich SARS-CoV und MERS-CoV, die aus dem Tierreservoir auf den Menschen übergegangen sind und bei einem deutlich größeren Anteil der Infizierten schwere virale Pneumonien mit tödlichem Verlauf auslösen [25, 28] . Obwohl die Mehrzahl der Infektionen mit den vier endemischen CoV nur leichte Atemwegserkrankungen verursacht, können alle HCoV auch schwere Hier steht eine Anzeige. Inwiefern diese sekundären Infektionen auf die intensivmedizinische Behandlung und Beatmung zurückzuführen sind oder ein spezifisches grundsätzliches Risiko einer CoV-Infektion darstellen, ist noch nicht verstanden. Jedoch ist eine spezifische Labordiagnostik bei Verdacht auf eine Infektion mit endemi-schen CoV bei harmlosem Verlauf und Patienten ohne besonderes Risiko für die Entstehung von Komplikationen auch nicht indiziert. Bei der typischerweise unspezifischen Klinik von MERS-CoV-Infektionen sollte auch die Möglichkeit einer Infektion mit anderen Pathogenen in Betracht gezogen werden [26] . RKI (2015) Schwere respiratorische Erkrankungen in Verbindung mit Middle East Respiratory Syndrome Coronavirus (MERS-CoV). cache = ./cache/cord-312670-hi3fjne4.txt txt = ./txt/cord-312670-hi3fjne4.txt === reduce.pl bib === id = cord-312305-ll29frwc author = Sun, Shihui title = Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date = 2020-11-11 pages = extension = .txt mime = text/plain words = 4720 sentences = 270 flesch = 52 summary = Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. We further characterized the in vivo replication dynamics of MASCp6 in both young and aged mice, and the results from qRT-PCR showed that high levels of SARS-CoV-2 subgenomic RNAs were persistent in the lung and tracheas till 4 day post infection (dpi) in aged mice (Fig. 1E) . The skewed age distribution of COVID-19 disease was reproduced in the MASCp36 infected mouse model where more severe symptoms were observed in aged mice when compared to young mice. In addition to the age-related skewed distribution of COVID-19, gender-related differences in distribution of COVID-19 disease is also recapitulated in this MASCp36 infected mouse model with increased susceptibility and enhanced pathogenicity observed in male mice when compared to their female counterparts. cache = ./cache/cord-312305-ll29frwc.txt txt = ./txt/cord-312305-ll29frwc.txt === reduce.pl bib === id = cord-314171-431buxxr author = Dariya, Begum title = Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients date = 2020-05-06 pages = extension = .txt mime = text/plain words = 6892 sentences = 421 flesch = 51 summary = In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. The mRNA and protein ACE2 expression levels are higher in these patients with cardiac disease, creating an increased risk for severe COVID-19 complications, including heart failure. After SARS-CoV-2 binds with ACE2, the virus degrades it, and thus the free angiotensin II induces acute lung injury [58] . Thus, targeting the binding site of the ACE2 receptor and SARS-CoV-2 with antibodies or therapeutic drugs might provide a successful treatment strategy. Moreover, this also increases the level of soluble ACE2 that competitively binds with SARS-CoV-2, causing delayed entry of the virus into cells and protecting against lung injury. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2 cache = ./cache/cord-314171-431buxxr.txt txt = ./txt/cord-314171-431buxxr.txt === reduce.pl bib === id = cord-314793-kb319t4c author = Borroni, Barbara title = Diaphragmatic myoclonus due to SARS-CoV-2 infection date = 2020-10-22 pages = extension = .txt mime = text/plain words = 1636 sentences = 101 flesch = 47 summary = Neurological signs in patients with SARS-CoV-2 have been widely reported, suggesting a neuroinvasive nature of virus [2, 3] . With the present observation, we report two cases of diaphragmatic myoclonus as neurological subacute manifestation of SARS-CoV-2 infection. The Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-020-04766-y) contains supplementary material, which is available to authorized users. Electromyographic recording confirmed rhythmic and synchronous contractions of the diaphragm at 3-Hz frequency as the cause of her abdominal movements (see Fig. 1 ), thus making the diagnosis of diaphragmatic myoclonus or van Leeuwenhoek's disease [5] . Here, we draw attention to two patients who developed focal diaphragmatic myoclonus after SARS-CoV-2 infection. Indeed, three cases of generalized myoclonus due to SARS-CoV-2 infection have been recently reported [10] . With the present report of two cases, we confirm and extend the neurotropic properties of SARS-CoV-2 virus and point out to a further neurological clinical manifestation of the infection. cache = ./cache/cord-314793-kb319t4c.txt txt = ./txt/cord-314793-kb319t4c.txt === reduce.pl bib === id = cord-312486-rumqopg0 author = Jacob, Chaim Oscar title = On the genetics and immunopathogenesis of COVID-19 date = 2020-09-10 pages = extension = .txt mime = text/plain words = 11514 sentences = 579 flesch = 44 summary = The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] . cache = ./cache/cord-312486-rumqopg0.txt txt = ./txt/cord-312486-rumqopg0.txt === reduce.pl bib === id = cord-314051-dr27bsvt author = Lother, Sylvain A. title = Preoperative SARS-CoV-2 screening: Can it really rule out COVID-19? date = 2020-06-23 pages = extension = .txt mime = text/plain words = 3121 sentences = 259 flesch = 56 summary = If viral carriage is not detected by testing, patients may proceed with elective surgery whereby signs and symptoms of coronavirus disease (COVID-19) may arise in the postoperative period, leading to adverse outcomes. 3 While screening with RT-PCR may detect some presymptomatic preoperative patients, the window of diagnostic utility is small, and careful interpretation of negative and positive test results must be considered prior to altering the course of therapy. A positive RT-PCR result identifies a group of patients who may be infected with SARS-CoV-2 and should have elective surgeries delayed. Si la présence virale n'est pas dépistée par un test, les patients peuvent aller de l'avant avec leur chirurgie non urgente, à la suite de laquelle les signes et symptômes d'une atteinte au coronavirus (COVID-19) pourraient survenir en période postopératoire, entraînant des devenirs défavorables. cache = ./cache/cord-314051-dr27bsvt.txt txt = ./txt/cord-314051-dr27bsvt.txt === reduce.pl bib === id = cord-318204-t024w7h6 author = Fang, Ferric C title = The Laboratory Diagnosis of COVID-19-- Frequently-Asked Questions date = 2020-06-08 pages = extension = .txt mime = text/plain words = 2976 sentences = 218 flesch = 51 summary = As communities attempt to re-open following periods of shutdown, the detection of both SARS-CoV-2 and specific antibodies recognizing the virus will become increasingly important as a means to assess infection and immunity in individuals and communities. In view of the less than ideal sensitivity of an NP swab to detect SARS-CoV-2 infection, it may be useful to repeat testing in a patient in whom the clinical suspicion is high (32) . Although the primary use of serologic tests is to determine prior exposure to SARS-CoV-2, the detection of specific antibodies may support the diagnosis of COVID-19 in a patient with a high clinical suspicion but negative PCR tests (57-59). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection cache = ./cache/cord-318204-t024w7h6.txt txt = ./txt/cord-318204-t024w7h6.txt === reduce.pl bib === id = cord-313517-5ipj2z86 author = Fung, Joshua title = Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans date = 2019-09-14 pages = extension = .txt mime = text/plain words = 2710 sentences = 149 flesch = 51 summary = Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus. Nucleic acid amplification test (NAAT, e.g., real-time reverse transcription quantitative polymerase chain reaction [real-time RT-qPCR]), virus isolation, transmission electron microscopy, immunohistochemistry, and serological methods (e.g., antigen capture enzyme-linked immunosorbent assay [ELISA] and immunofluorescence assay [IFA] ) have been developed and used for MERS-CoV diagnosis [2] [3] [4] [5] [6] [7] . cache = ./cache/cord-313517-5ipj2z86.txt txt = ./txt/cord-313517-5ipj2z86.txt === reduce.pl bib === id = cord-314445-4cb4a9r5 author = McNamara, Ryan P. title = High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1960 sentences = 131 flesch = 53 summary = This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. The current COVID-19 pandemic is an urgent public health emergency with over 112,000 deaths in the United States (U.S.) alone. At a CP ≥35 most positive samples still yielded reads that mapped to the target genome 227 and thus allowed detection of SARS-CoV-2 sequences; however, the results were less consistent, 228 and coverage was more variable. In sum, this study generated exhaustive SNV information representing the introduction and 325 spread of SARS-CoV-2 across a suburban low-density area in the Southern U.S. All samples were 326 from symptomatic cases and the majority of genomes clustered with variants that predominate the 327 outbreak in the U.S., rather than Europe or China. cache = ./cache/cord-314445-4cb4a9r5.txt txt = ./txt/cord-314445-4cb4a9r5.txt === reduce.pl bib === id = cord-314669-lvibjx97 author = Shang, Guifang title = Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 date = 2007-11-26 pages = extension = .txt mime = text/plain words = 4044 sentences = 186 flesch = 53 summary = title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 STUDY DESIGN AND METHODS: Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. RESULTS: Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 Then, using this information and information on the asymptomatic or subclinical SARS-CoV infection-to-clinically confirmed SARS ratio (R), the proportion of infected individuals who remain asymptomatic (A), and the population size, we estimated the risk of SARS-CoV transmission by transfusion from a unit of blood donated at time t during the epidemic. cache = ./cache/cord-314669-lvibjx97.txt txt = ./txt/cord-314669-lvibjx97.txt === reduce.pl bib === id = cord-316702-dj2fo8sn author = Vignesh, Ramachandran title = Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date = 2020-09-30 pages = extension = .txt mime = text/plain words = 3250 sentences = 169 flesch = 45 summary = Since many studies from different geographical locations are documenting preexisting immunity to SARS-CoV-2, it will be important to define specificities of these T and B cell immune response carefully to assess their association with COVID-19 disease severity. This preexisting cross-reactive T and B cell immunity to SARS-CoV-2 may have wide implications as this could explain differential clinical outcomes in COVID-19 patients, disease severity, vaccine development, and important in accessing herd immunity for SARS-CoV-2 viral infection/COVID-19 disease. Several studies have provided strong evidence for the importance of SARS-CoV-2 specific CTLs, and T helper cells in mild and moderate patients compared to severe COVID-19 disease (27, 28, (31) (32) (33) . Several studies have provided strong evidence for the importance of SARS-CoV-2specific neutralizing antibodies in association with less disease severity in COVID-19 patients (38, 39) . A recent modelling study has estimated that about one in five individuals worldwide would be at increased risk of severe COVID-19, upon infection with SARS-CoV-2, owing to the underlying conditions. cache = ./cache/cord-316702-dj2fo8sn.txt txt = ./txt/cord-316702-dj2fo8sn.txt === reduce.pl bib === id = cord-314135-udce22id author = Geisslinger, Franz title = Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa? date = 2020-07-06 pages = extension = .txt mime = text/plain words = 6414 sentences = 379 flesch = 46 summary = The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. The main symptoms of COVID-19, the lung disease following SARS-CoV-2 infection are fever, cough, shortness of breath and respiratory distress syndrome with risk for septic shock. Preliminary evidence suggests that such a cytokine storm in response to infection with SARS-CoV-2 is a major factor, promoting severe COVID-19 progress and subsequently disease fatality [8, 12] . Chemotherapy-and radiation therapy-induced immunosuppression is a major risk factor for cancer patients to acquire a severe and probably fatal SARS-CoV-2 infection. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS † cache = ./cache/cord-314135-udce22id.txt txt = ./txt/cord-314135-udce22id.txt === reduce.pl bib === id = cord-315064-2mgv9j6n author = Escher, Felicitas title = Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies date = 2020-06-12 pages = extension = .txt mime = text/plain words = 3813 sentences = 241 flesch = 48 summary = Accordingly, we prospectively analysed endomyocardial biopsies (EMBs) from a cohort of 104 samples of patients with suspected myocarditis or unexplained heart disease for the presence of SARS-CoV-2 RNA by RT-qPCR and hints for histopathological injury. Up to 8 EMBs each of 104 patients [mean age: 57.90 ± 16.37 years; left ventricular ejection fraction (LVEF): 33.7 ± 14.6%, sex: n = 79 male/25 female] with suspected myocarditis or unexplained heart failure were analysed between 3 February and 26 March 2020 in German clinical centres in accordance with SARS-CoV2 spread in Germany. In this study, we established for the first time the evidence of SARS-CoV-2 genome detection in 5 of 104 EMBs of patients with suspected myocarditis or unexplained heart failure. Our finding of SARS-CoV-2 genome detection in EMBs of patients suffering from myocarditis/inflammatory cardiomyopathy cannot rule out or confirm the infection of cardiac cells but revealed incremental insights into organ-specific infection of SARS-CoV-2 using possibly macrophage migration as a shuttle from the lung to the heart. cache = ./cache/cord-315064-2mgv9j6n.txt txt = ./txt/cord-315064-2mgv9j6n.txt === reduce.pl bib === id = cord-316126-j51dik7f author = Zhang, X. Sophie title = SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles date = 2020-10-28 pages = extension = .txt mime = text/plain words = 12434 sentences = 576 flesch = 42 summary = title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2's mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. This review attempts to summarize current cumulative data on SARS-CoV-2's modes of transmission and identify gaps in research while offering preliminary answers to the question on everyone's mind: is the airborne route significant and should we modify our COVID-19 PPE recommendations for frontline workers in low-risk settings? Given that substantial disagreement persists on the importance of natural aerosol generation by COVID-19 patients, and consequently, the necessary level of respiratory protection in non-AGP contexts, our review will focus on transmission and PPE in low-risk health care settings. cache = ./cache/cord-316126-j51dik7f.txt txt = ./txt/cord-316126-j51dik7f.txt === reduce.pl bib === id = cord-314451-mqnqjn0c author = Roberts, Anjeanette title = A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date = 2007-01-12 pages = extension = .txt mime = text/plain words = 9794 sentences = 433 flesch = 48 summary = To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. cache = ./cache/cord-314451-mqnqjn0c.txt txt = ./txt/cord-314451-mqnqjn0c.txt === reduce.pl bib === id = cord-312664-tgpaidhp author = Liang, Julia title = Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex date = 2020-05-28 pages = extension = .txt mime = text/plain words = 3050 sentences = 189 flesch = 52 summary = title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. Further, molecular dynamics simulations highlight the stability of the interaction of the α-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (ΔG = -25.2 and -22.3 kcal/mol for protomers A and B). Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . cache = ./cache/cord-312664-tgpaidhp.txt txt = ./txt/cord-312664-tgpaidhp.txt === reduce.pl bib === id = cord-318164-6rqi17oz author = Paoli, D. title = Sperm cryopreservation during the SARS-CoV-2 pandemic date = 2020-10-10 pages = extension = .txt mime = text/plain words = 3258 sentences = 177 flesch = 48 summary = This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation. This study thus aimed to evaluate the safety of sperm cryopreservation of cancer patients referred to our sperm bank after the onset of the pandemic in Italy through the assessment of the risk of SARS-CoV-2 exposure and, in selected volunteers, viral RNA testing of semen samples. This was further confirmed by testing seminal fluid samples from 10 asymptomatic cancer patients for SARS-CoV-2 RNA. cache = ./cache/cord-318164-6rqi17oz.txt txt = ./txt/cord-318164-6rqi17oz.txt === reduce.pl bib === id = cord-315685-ute3dxwu author = Ehaideb, Salleh N. title = Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review date = 2020-10-06 pages = extension = .txt mime = text/plain words = 5542 sentences = 352 flesch = 48 summary = The systematic search identified 101 studies and 326 preprints, of which 400 articles were excluded because they were reviews, non-original articles, unrelated to the COVID-19 infection, or experimental animals that do not support SARS-CoV-2 replication such as pigs, ducks, and chickens ( Fig. 1 and Additional file 2). The aims were to investigate the pathogenesis of COVID-19 (n = 15), testing drugs and vaccines (n = 14), the host Table 1 Search strategy and selection criteria We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research describing or using an animal model of SARS-CoV-2 induced COVID published in English from January 1, 2020, to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). cache = ./cache/cord-315685-ute3dxwu.txt txt = ./txt/cord-315685-ute3dxwu.txt === reduce.pl bib === id = cord-315288-fcx4q6mp author = Hussain, Mohammed Hassan title = Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body date = 2020-08-27 pages = extension = .txt mime = text/plain words = 1566 sentences = 105 flesch = 62 summary = We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. Patients with front of neck airways, either in the form of a laryngectomy or tracheostomy stoma site, present a challenge in terms of testing for SARS-CoV-2. There is a need for clear guidance on how to test patients with front of neck airways for SARS-CoV-2. cache = ./cache/cord-315288-fcx4q6mp.txt txt = ./txt/cord-315288-fcx4q6mp.txt === reduce.pl bib === id = cord-319184-voc0eqb9 author = Abduljalil, Jameel M. title = Laboratory diagnosis of SARS-CoV-2: available approaches and limitations date = 2020-06-14 pages = extension = .txt mime = text/plain words = 1115 sentences = 101 flesch = 44 summary = Clinical 397 evaluation of the cobas SARS-CoV-2 test and a diagnostic platform switch during 48 398 hours in the midst of the COVID-19 pandemic Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-406 19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro Rapid and visual detection of 2019 458 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal 459 amplification assay Transcription Loop-Mediated Isothermal Amplification Assays Targeting SARS-CoV-2 Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of 467 SARS-CoV-2 Development of a reverse 469 transcription-loop-mediated isothermal amplification as a rapid early-detection method for 470 novel SARS-CoV-2 Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Development and clinical application of a 500 rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Novel Antigen-Based Rapid Detection Test for the Diagnosis of SARS-CoV-2 in Serological immunochromatographic 525 approach in diagnosis with SARS-CoV-2 infected COVID-19 patients cache = ./cache/cord-319184-voc0eqb9.txt txt = ./txt/cord-319184-voc0eqb9.txt === reduce.pl bib === id = cord-315085-rucfowvv author = Sekulic, Miroslav title = Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases date = 2020-05-26 pages = extension = .txt mime = text/plain words = 5025 sentences = 302 flesch = 47 summary = In this study we report postmortem findings and detection and sequencing of SARS-CoV-2 viral RNA from formalin-fixed paraffinembedded (FFPE) samples of multiple organs collected in 2 patients with antemortem detection of SARS-CoV-2. The patient's medical history was otherwise notable for dementia, radiologic evidence of a left lung mass (managed with hospice care), coronary artery disease (status post coronary artery bypass grafting), atrial fibrillation (biventricular pacemaker implanted), congestive heart failure, peripheral artery disease (status post iliac stenting), diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, gout, smoking, cerebrovascular accidents, and urinary tract infections. On day 1 after admission, ❚Image 2❚ (Case 1) Postmortem microscopic examination of the lungs showed diffuse alveolar damage characterized by hyaline membrane formation (A, ×100) and scattered squamous metaplasia of distal airways (B, ×100) on a background of emphysematous changes. cache = ./cache/cord-315085-rucfowvv.txt txt = ./txt/cord-315085-rucfowvv.txt === reduce.pl bib === id = cord-319194-ukuia48s author = Liò, Pietro title = Phylogenomics and bioinformatics of SARS-CoV date = 2004-02-04 pages = extension = .txt mime = text/plain words = 4488 sentences = 201 flesch = 45 summary = Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Figure 1 shows the maximum likelihood tree produced using a set of homologous replicases from five SARS-CoV strains, 12 other coronaviruses representing both groups 1 and 2 of the genus [2, 3] , one torovirus (Breda virus) and one okavirus [yellow head (YH) virus], which were determined to most closely represent the consensus coronavirus sequence by a PSI-Blast search [12] . cache = ./cache/cord-319194-ukuia48s.txt txt = ./txt/cord-319194-ukuia48s.txt === reduce.pl bib === id = cord-317952-4oa9hfb4 author = Bourgonje, Arno R. title = Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) date = 2020-05-17 pages = extension = .txt mime = text/plain words = 12082 sentences = 664 flesch = 38 summary = ACE2 was highly expressed on lung alveolar epithelial cells and small intestinal epithelial cells, consistent with potential routes of viral transmission of SARS-CoV-2, as both respiratory and gastrointestinal systems share interfaces with the external environment. ACE2 expression in the lungs and SARS-CoV-2 viral load have been suggested to increase with age, which might provide an explanation to the higher disease severity observed in older patients with COVID-19 [35] . Both SARS-CoV-2 infection, directly mediated by ACE2 expression and activity, and superimposed disease triggers may be responsible for the observed pathological findings. Additionally, another study reported purpura and livedo racemosa in several severely affected COVID-19 patients with small vessel thrombosis with co-localization of complement and SARS-CoV-2 spike proteins on histopathology [148] .This indicates direct viral infection of the small skin vessels. Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone-inhibitors: Potential implications for coronavirus SARS-CoV-2 infected patients cache = ./cache/cord-317952-4oa9hfb4.txt txt = ./txt/cord-317952-4oa9hfb4.txt === reduce.pl bib === id = cord-317786-iv1br2oj author = Waterfield, T. title = Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study. date = 2020-09-02 pages = extension = .txt mime = text/plain words = 3769 sentences = 271 flesch = 54 summary = Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. Participants and their parents provided information at enrollment relating to age, sex, previous health and potential predictors of SARS-CoV-2 infection including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/antibody testing. Seroprevalence of SARS-CoV-2 antibodies in children of healthcare workers-A prospective multicentre cohort study protocol -Accepted for publication cache = ./cache/cord-317786-iv1br2oj.txt txt = ./txt/cord-317786-iv1br2oj.txt === reduce.pl bib === id = cord-317355-z5tk3v3b author = Dunker, Susanne title = No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread date = 2020-10-13 pages = extension = .txt mime = text/plain words = 1954 sentences = 139 flesch = 62 summary = title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread Air samples collected at our measuring station in Leipzig and purified pollen were analyzed for SARS-CoV-2 typical signals or for virus-induced cytopathic effects, to test if the virus could bind to bioaerosols and if so, whether these complexes are infectious. We therefore aimed at investigating whether SARS-CoV-2 can bind to pollen or other kind of particulate matter within bioaerosols sampled at our station in Leipzig and if so, whether these complexes are infectious. In none of these samples SARS-CoV-2 typical For a detailed analysis of a possible correlation between concentrations of the most abundant pollen, particulate matter and registered Covid-19 cases, a correlation matrix was created with R (package "PerformanceAnalytics") (Fig. 2) . cache = ./cache/cord-317355-z5tk3v3b.txt txt = ./txt/cord-317355-z5tk3v3b.txt === reduce.pl bib === id = cord-324557-4u8dja0n author = Leblanc, Jean‐François title = Risk of Transmission of Severe Acute Respiratory Syndrome Coronavirus‐2 by Transfusion: A Literature Review date = 2020-08-15 pages = extension = .txt mime = text/plain words = 3044 sentences = 195 flesch = 50 summary = Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biological sample and infectivity requires a minimal RNA load, which is rarely, if at all observed, in blood components. More specifically, PubMed was interrogated with a series of queries aimed at identifying references that relate to COVID-19/SARS-CoV-2 and the detection of viral genomic material in blood, plasma, or serum. From this screen, 23 references reporting any data or stating any information on the detection of SARS-CoV-2 genomic material in human blood, plasma, or serum, were selected ( Table 2) . An exhaustive search strategy led to the identification of 23 references reporting data on the detection of SARS-CoV-2 genomic material in blood components (Table 2) . cache = ./cache/cord-324557-4u8dja0n.txt txt = ./txt/cord-324557-4u8dja0n.txt === reduce.pl bib === id = cord-319877-izn315hb author = de Wit, Emmie title = SARS and MERS: recent insights into emerging coronaviruses date = 2016-06-27 pages = extension = .txt mime = text/plain words = 9387 sentences = 424 flesch = 43 summary = Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. The downregulation of ACE2 results in the excessive production of angiotensin II by the related enzyme ACE, and it has been suggested that the stimulation of type 1a angiotensin II receptor and Middle East respiratory syndrome coronavirus (MERS-CoV) encode two large polyproteins, pp1a and pp1ab, which are proteolytically cleaved into 16 non-structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have developed mechanisms to interfere with these signalling pathways, as shown; these subversion strategies involve both structural proteins (membrane (M) and nucleocapsid (N)) and non-structural proteins (nsp1, nsp3b, nsp4a, nsp4b, nsp5, nsp6 and papain-like protease (PLpro); indicated in the figure by just their nsp numbers and letters). cache = ./cache/cord-319877-izn315hb.txt txt = ./txt/cord-319877-izn315hb.txt === reduce.pl bib === id = cord-321851-ku4z34lu author = Alosaimi, Bandar title = MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract date = 2020-02-29 pages = extension = .txt mime = text/plain words = 5619 sentences = 299 flesch = 45 summary = Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. The lower respiratory tract samples from MERS-CoV infected patients and healthy non-infected controls were used to quantify expression levels of the main 12 human pro-inflammatory cytokines and chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, and GM-CSF). A side-by-side analysis of the data derived from the RT 2 -PCR profiling of pulmonary Th1/Th2 responses showed that genes encoding Th1 and Th2-related cytokines and chemokines were largely downregulated in the lower respiratory tract of MERS-CoV infected patients. Therefore, the high expression of inflammatory cytokines and downregulation of the Th1 and Th2 immune responses in the lower respiratory tracts of MERS-CoV infected patients may contribute to a more severe infection, higher case fatality, lung inflammation, and immunopathology. cache = ./cache/cord-321851-ku4z34lu.txt txt = ./txt/cord-321851-ku4z34lu.txt === reduce.pl bib === id = cord-318316-9unfl966 author = Ortega, Joseph T. title = Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies date = 2020-10-23 pages = extension = .txt mime = text/plain words = 4022 sentences = 236 flesch = 46 summary = SUMMARY: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Another early target evaluated against SARS-CoV-2 is a cellular protease related to the priming of the spike protein (S), which exposes the fusion motive and allows the release of viral RNA into the cytosol. HCQ, hydroxychloroquine; RdRp, RNA-dependent RNA polymerase; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; ORF, open reading frame. Favipiravir, another antiviral agent with broad activity against other RNA viruses by inhibiting the RdRp, halting viral replication, was evaluated against SARS-CoV-2, showing effects in vitro and in vivo [43] [44] [45] . cache = ./cache/cord-318316-9unfl966.txt txt = ./txt/cord-318316-9unfl966.txt === reduce.pl bib === id = cord-321918-9jwma2y6 author = Xiu, Siyu title = Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities date = 2020-06-15 pages = extension = .txt mime = text/plain words = 10526 sentences = 621 flesch = 52 summary = The spike protein can be divided into two domains; S1 is responsible for angiotensin-converting enzyme II(ACE2) recognition, the recently identified host cell receptor, and S2 mediates membrane fusion (Figure 2 ). 98 99 On the basis of this approach, they identified two small molecules, TGG (12, Table 4 ) and luteolin (13) , that can bind avidly to the SARS-CoV S2 protein and inhibit viral entry of SARS-CoV into Vero E6 cells with IC 50 values of 4.5 and 10.6 μM, respectively. 113 A high-throughput screen (HTS) of a 1000-compound library that resulted in the identification of MDL28170 (17 , Table 4 ) by Bates et al., and in an antiviral activity assay, 17 specifically inhibited cathepsin L-mediated substrate cleavage and blocked SARS-CoV viral entry, with an IC 50 value of 2.5 nM and EC 50 value in the range of 100 nM. cache = ./cache/cord-321918-9jwma2y6.txt txt = ./txt/cord-321918-9jwma2y6.txt === reduce.pl bib === id = cord-324480-7u5lh4jx author = Sharma, A. title = Structural stability of SARS-CoV-2 degrades with temperature date = 2020-10-14 pages = extension = .txt mime = text/plain words = 1541 sentences = 88 flesch = 51 summary = Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. However an understanding of how SARS-CoV-2 survives different environmental conditions is still incomplete and mechanisms of virus particle degradation are poorly mapped out. A key challenge in studying SARS-CoV-2 is the extreme level of threat associated with the live virus and the resultant need for high safety standards for such work. Here we used this technology to study the stability of the viral envelope and associated proteins (M, E, and S) under different environmental conditions. Environmental stability of SARS-CoV-2 on different types of surfaces under indoor and seasonal climate conditions cache = ./cache/cord-324480-7u5lh4jx.txt txt = ./txt/cord-324480-7u5lh4jx.txt === reduce.pl bib === id = cord-322811-6lebh7ca author = Baig, Mirza S. title = Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells date = 2020-06-26 pages = extension = .txt mime = text/plain words = 4119 sentences = 245 flesch = 53 summary = METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. Currently, the computational analysis of structural differences in human ACE2 impact its binding to the SARS-CoV-2 spike protein, which thereby lays a foundation for the design and development of ACE2-based peptide inhibitors of SARS-CoV-2 [47] [48] [49] . After a detailed analysis of interface residues, a small stretch of the ACE2 PD N-terminal region (23-amino acids: Glu23 to Leu45) was found to be interacting majorly with the SARS-CoV-2 spike protein ( Fig. 2 and Table 1 ). Computational alanine (A) scanning was performed to identify the critically important amino acids of the 23aa peptide inhibitor involved in binding to the SARS-CoV-2 spike protein. cache = ./cache/cord-322811-6lebh7ca.txt txt = ./txt/cord-322811-6lebh7ca.txt === reduce.pl bib === id = cord-321855-7b1c2xdh author = Alshami, Alanoud title = Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date = 2020-10-30 pages = extension = .txt mime = text/plain words = 3380 sentences = 190 flesch = 56 summary = title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. cache = ./cache/cord-321855-7b1c2xdh.txt txt = ./txt/cord-321855-7b1c2xdh.txt === reduce.pl bib === id = cord-322051-89wgv100 author = Tanasa, Ingrid Andrada title = Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known? date = 2020-05-28 pages = extension = .txt mime = text/plain words = 2260 sentences = 132 flesch = 44 summary = This study summarizes the existing data regarding the association of anosmia and ageusia with the SARS-CoV-2 infection. In a retrospective observational study, Klopfenstein et al (20) reported that 54 patients (47%) with confirmed SARS-CoV-2 infection developed anosmia, 4.4 (±1.9) days after infection onset, and that was the third symptom to manifest in 38% (22/52) of the cases. Some authors reported three mechanisms for anosmia in COVID-19 patients: i) local infection of support cells and vascular pericytes in the nose and olfactory bulb that may affect the function of bipolar neurons or mitral cells; ii) damage to support cells in the sensory epithelium that may indirectly influence the signaling pathway from sensory neurons to the brain; and iii) damage to sustentacular cells and Bowman's gland cells that could lead to diffuse morphological damage to the olfactory sensory epithelium and altering of smell perception (28, 29) . Further research is needed to demonstrate the association between anosmia and ageusia with SARS-CoV-2 infection, the clinical manifestations determined by variants of ACE2 receptor, and recovery rates of olfactory and gustative dysfunction, and specific treatment protocols of these manifestations. cache = ./cache/cord-322051-89wgv100.txt txt = ./txt/cord-322051-89wgv100.txt === reduce.pl bib === id = cord-323061-0i5w7vm9 author = Kharel Sitaula, Ranju title = Unfolding COVID-19: Lessons-in-Learning in Ophthalmology date = 2020-09-28 pages = extension = .txt mime = text/plain words = 4845 sentences = 266 flesch = 51 summary = 10 Epiphora and Conjunctival redness had been the first manifestation of SARS-CoV-2 infection in 3 reported cases till date which includes a member of National expert on pneumonia during his visit to endemic areas of Wuhan and an anesthesiologist contracting the virus from a known patient of novel coronavirus pneumonia during intubation in Italy; similarly, it was reported in a nurse working in the emergency department of ophthalmology who presented with viral conjunctivitis and watering as a first sign. Hence, our knowledge and understanding about the SARS-CoV-2 virus, modes of entry to the eye, hypothesis on the interaction with the Renin-Angiotensin System (RAS) system and ACE2 receptor and ocular pathogenesis and RT PCR analysis from the ocular secretions have been summarized below using text, tables, diagrams, and flowcharts. cache = ./cache/cord-323061-0i5w7vm9.txt txt = ./txt/cord-323061-0i5w7vm9.txt === reduce.pl bib === id = cord-318934-dxipu00r author = Matsuyama, Shutoku title = Enhancement of SARS-CoV Infection by Proteases date = 2006 pages = extension = .txt mime = text/plain words = 1861 sentences = 109 flesch = 56 summary = Moreover, SARS-CoV entry from the cell surface mediated by proteases was a 100-fold more efficient infection than entry through endosomes. However, no S2 band was detected in SARS-CoV infected cells treated with proteases that failed to induce fusion. 3 stated that SARS-CoV is able to enter cells directly from their surface, if receptor-bound virus is treated with trypsin and other proteases that induce fusion. Treatment of VeroE6 cells with bafilomycin was shown to suppress SARS-CoV infection via the endosomal pathway to less than 1/100 (Fig. 2) . Pseudotype VSV bearing SARS-CoV S protein infection was also facilitated in bafilomycin-treated VeroE6 cells after treatment with proteases that induce fusion of SARS-CoV infected cells. These observations suggest that proteases that facilitate SARS-CoV entry from the cell surface support efficient SARS-CoV infection. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry cache = ./cache/cord-318934-dxipu00r.txt txt = ./txt/cord-318934-dxipu00r.txt === reduce.pl bib === id = cord-320619-r466dc5t author = Chand Dakal, Tikam title = SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 date = 2020-11-05 pages = extension = .txt mime = text/plain words = 3843 sentences = 210 flesch = 46 summary = title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 The higher expression of integrins in lungs along with their previously known high binding affinity (∼K(D) = 4.0nM) for virus RGD motif could serve as a possible explanation for high infectivity of SARS-CoV-2. This study is the first study to present striking evidence (substantiated by existing facts in literature) favoring the role of calcium and other divalent ions (magnesium, manganese etc.) in RGD-integrins mediated virus attachment with the host cells for and that lowering the concentration of calcium and other divalent ions in lungs could be a possible mechanism to avert SARs-CoV-2 infection and invasion. A number of motifs were predicted in the spike protein sequence such as RGD (from 403-405 aa in receptor binding domain of SARS-CoV-2) ( Table 2 ). cache = ./cache/cord-320619-r466dc5t.txt txt = ./txt/cord-320619-r466dc5t.txt === reduce.pl bib === id = cord-319241-div9rzax author = Singh, Bhuchitra title = Severe Acute Respiratory Syndrome‐Corona Virus‐2 (SARS‐CoV‐2) and its Effect on Gametogenesis and Early Pregnancy date = 2020-09-23 pages = extension = .txt mime = text/plain words = 4386 sentences = 305 flesch = 50 summary = There is also evidence of significant placental pathology in SARS‐CoV‐2 infection, but it is unclear what effects there may be for early pregnancy, though available data suggest less severe effects compared to other respiratory virus outbreaks. We searched for articles that contained information related to SARS-CoV-2 and reproductive tissues (ovaries, testes), gametes, placentation, and early pregnancy in humans. Our search phrases included: "severe acute respiratory syndrome coronavirus 2", "2019 ncov", "sarscov 2", "SARS-Cov-2", "pregnancy", "gravidity", "abortion", "germ cells", "oocytes", "gametes", "embryonic structures", "embryo", "fertility", "testes", "miscarriage"(See Appendix 1 for completed list of databases search strategy and Figure 1 for PRISMA table). Specifically, 10 women with severe COVID-19 were tested or SARS-CoV-2 in vaginal fluid, with all samples negative for virus [48] . Another study performed during the 2002-2003 SARS pandemic showed that 4 of 7 (57%) pregnant women infected with SARS-CoV had a spontaneous miscarriage in the first trimester of pregnancy [55] , though notably no viral inclusion bodies or particles were detected in the products of conception. cache = ./cache/cord-319241-div9rzax.txt txt = ./txt/cord-319241-div9rzax.txt === reduce.pl bib === id = cord-322908-e3gok0ot author = Huang, Fangfang title = A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) date = 2020-05-20 pages = extension = .txt mime = text/plain words = 5056 sentences = 275 flesch = 42 summary = In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19. In this review, we summarized potential Chinese herbal medicines ( Table 2 ) that may treat COVID-19 by targeting proteins such as Spike protein, ACE2, 3CLpro, PLpro and RdRp. We also predicted the binding affinities between these compounds and COVID-19 related targets by molecular docking, with a focus on six compounds: quercetin, andrographolide, glycyrrhizic acid, baicalin, patchouli alcohol, and luteolin. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial cache = ./cache/cord-322908-e3gok0ot.txt txt = ./txt/cord-322908-e3gok0ot.txt === reduce.pl bib === id = cord-321358-plxz5mkg author = Zheng, Jun title = SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat date = 2020-03-15 pages = extension = .txt mime = text/plain words = 4759 sentences = 251 flesch = 53 summary = An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. CoVs have been identified in both avian hosts and various mammals, including bat, camels, dogs and masked palm civets, and are previously regarded as pathogens that only cause mild diseases in the immunocompetent people until the emergence of the coronavirus causing severe acute respiratory syndrome (SARS-CoV) in late of 2002 [3] [4] [5] [6] . cache = ./cache/cord-321358-plxz5mkg.txt txt = ./txt/cord-321358-plxz5mkg.txt === reduce.pl bib === id = cord-321166-nvphu1fm author = Thomson, Emma C. title = The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date = 2020-11-05 pages = extension = .txt mime = text/plain words = 9813 sentences = 514 flesch = 55 summary = We find that the N439K mutation is associated with a similar clinical spectrum of disease and slightly higher viral loads in vivo compared with isolates with the wild-type N439 residue, and that it results in immune escape from polyclonal sera from a proportion of recovered individuals and a panel of neutralizing mAbs. N439K provides a sentinel example of immune escape, indicating that RBM variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of mAbs. Long term control of the pandemic will require systematic monitoring of immune escape variants and selection of strategies that address the variants circulating in targeted populations. Fitness of this variant, N439K, was demonstrated by repeated emergence by convergent evolution, spread to multiple countries and significant representation in the SARS-CoV-2 sequence databases, the fact that the N439K RBD retains a high affinity interaction with the hACE2 receptor, efficient viral replication in cultured cells, and no disease attenuation in a large cohort of infected individuals. cache = ./cache/cord-321166-nvphu1fm.txt txt = ./txt/cord-321166-nvphu1fm.txt === reduce.pl bib === id = cord-322129-uyswj4ow author = Melin, Amanda D. title = Comparative ACE2 variation and primate COVID-19 risk date = 2020-10-27 pages = extension = .txt mime = text/plain words = 6310 sentences = 305 flesch = 47 summary = Infection studies of rhesus monkeys, long-tailed macaques, and vervets as biomedical models have made it clear that at least some nonhuman primate species are permissive to SARS-CoV-2 infection and develop symptoms in response to infection that resemble those of humans following the development of COVID-19, including similar age-related effects [11] [12] [13] [14] [15] [16] . We assessed the variation at amino acid residues identified as critical for ACE2 recognition by the SARS-CoV-2 RBD and undertook an analysis of positive selection and protein modeling to gauge the potential for adaptive differences and the likely effects of protein variation. In particular, the twelve sites in the ACE2 protein that are critical for binding of the SARS-CoV-2 virus are invariant across the Catarrhini, which includes great apes, gibbons, and monkeys of Africa and Asia (Fig. 1) . cache = ./cache/cord-322129-uyswj4ow.txt txt = ./txt/cord-322129-uyswj4ow.txt === reduce.pl bib === id = cord-320935-3n157yl4 author = Kumar, Manish title = Making Waves Perspectives of Modelling and Monitoring of SARS-CoV-2 in Aquatic Environment for COVID-19 Pandemic date = 2020-09-12 pages = extension = .txt mime = text/plain words = 6613 sentences = 346 flesch = 44 summary = This paper aims to collate information on recent developments on WBE in monitoring the trend of community-scale SARS-CoV-2 prevalence as well as models to predict virus spread and transmission among populations. While several studies have identified the presence of SARS-CoV-2 in the faecal matter of corona-infected patients [35, 36] , there is a growing concern on the transmission of the virus through water treatment plants (WTPs) and WWTPs. Several studies also detected the genetic material of the virus in raw wastewater across the globe [22, 26, 27] . These studies provided enough excellent reasons for modelling the spread of 2019-nCoV with the external environmental conditions, assuming that the cases of infection will decrease through secondary infection routes due to the inactivation of the virus on different surfaces; however, the possibility of transmission via direct contact remains unchanged. cache = ./cache/cord-320935-3n157yl4.txt txt = ./txt/cord-320935-3n157yl4.txt === reduce.pl bib === id = cord-322837-tqgwgvo0 author = Gable, Lance title = Legal and Ethical Implications of Wastewater SARS-CoV-2 Monitoring for COVID-19 Surveillance date = 2020-06-24 pages = extension = .txt mime = text/plain words = 1909 sentences = 104 flesch = 47 summary = Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing, must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations. The proposed use of wastewater screening to detect SARS-CoV-2 viral RNA has the potential to greatly enhance our technical capabilities to identify, track, pinpoint, and quantify 32 Second, public health authorities could use this information to justify increased testing among people living in homes or working at sites close to where the virus has been found in wastewater, or to implement neighborhood-wide screening programs in these areas. Wastewater screening for SARS-CoV-2 could provide an important tool to detect new outbreaks of COVID-19 and to target resources to intervene to stop the spread of the disease; however, scientific research must establish the efficacy of such testing in identifying communitybased COVID-19 infections before its use can be considered as the basis for public policy. cache = ./cache/cord-322837-tqgwgvo0.txt txt = ./txt/cord-322837-tqgwgvo0.txt === reduce.pl bib === id = cord-323666-t7cshj05 author = Cegolon, L. title = Nasal Disinfection for the Prevention and Control of COVID-19: A Scoping Review on Potential Chemo-preventive Agents. date = 2020-08-18 pages = extension = .txt mime = text/plain words = 6187 sentences = 339 flesch = 46 summary = Figure 1 reports the corresponding changes as percentage or odds; the latter detects the improvement of the index score better than the former because it is able to overcome the ceiling effects J o u r n a l P r e -p r o o f Therefore, in addition to an effective treatment for symptomatic patients, there is an urgent need to abate the carriage of SARS-CoV-2 in the human nasal cavity of asymptomatic/pre-symptomatic individuals, in order to contain the transmission of the novel coronavirus within the community. The abstracts of the original articles were explored for the following terms: mechanism(s) of action, tolerability and any evidence of toxic effects or selection of resistant strains, whether the treatment was tested in vitro (in particular against SARS-CoV-2), or reached the clinical trials stage, or is currently marketed/promoted/sold. cache = ./cache/cord-323666-t7cshj05.txt txt = ./txt/cord-323666-t7cshj05.txt === reduce.pl bib === id = cord-323093-u3ozc9ry author = Rathnayake, Athri D. title = 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date = 2020-08-19 pages = extension = .txt mime = text/plain words = 7158 sentences = 362 flesch = 56 summary = After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection. cache = ./cache/cord-323093-u3ozc9ry.txt txt = ./txt/cord-323093-u3ozc9ry.txt === reduce.pl bib === id = cord-322957-clf8f90t author = Crespo, Javier title = Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG date = 2020-04-28 pages = extension = .txt mime = text/plain words = 5297 sentences = 364 flesch = 51 summary = The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. cache = ./cache/cord-322957-clf8f90t.txt txt = ./txt/cord-322957-clf8f90t.txt === reduce.pl bib === id = cord-321901-zpi7uis1 author = Roberts, Anjeanette title = Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK date = 2006-11-30 pages = extension = .txt mime = text/plain words = 6600 sentences = 311 flesch = 40 summary = Scientists at the WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, discussed many aspects of research pertaining to the use of animal models in vaccine development including available animal models, suitability of the various models, correlates of protection, critical components of potential vaccines, and the potential for disease enhancement in vaccinated animals following exposure to SARS-CoV. It may actually be worthwhile to enhance the virulence of a SARS-CoV isolate by serial passages in an animal model to produce a challenge virus stock for vaccine studies that would elicit more reproducible disease in the animals. Although none of the studies to date have shown enhanced respiratory disease following SARS-CoV challenge in previously immunized animals, further studies in this area are warranted in view of some of the available in vitro data. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice cache = ./cache/cord-321901-zpi7uis1.txt txt = ./txt/cord-321901-zpi7uis1.txt === reduce.pl bib === id = cord-324919-ciamusjs author = Scialo, Filippo title = ACE2: The Major Cell Entry Receptor for SARS-CoV-2 date = 2020-11-10 pages = extension = .txt mime = text/plain words = 5356 sentences = 257 flesch = 42 summary = Since the beginning of the COVID-19 pandemic, hypertension and diabetes have been correlated with higher risk of mortality, and initial reports speculated that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), which are commonly used therapeutic agents for these conditions, would up-regulate ACE2 expression, thus increasing the risk of severe illness [37] . Binding of S1 subunit of the Spike protein of SARS-CoV-2 to the ACE2 receptor triggers the cleavage of ACE2 by ADAM17/tumor necrosis factorconverting enzyme (TACE) at the ectodomain sites [41] and a soluble form that retains its catalytic activity (sACE2) is produced [42] . ACE2 shedding can be stimulated by proinflammatory cytokines such as IL-1β and tumor necrosis factor (TNF)-α, and endotoxin [47] that could result in a positive effect reducing SARS-CoV-2 entry, but at the same time, may cause an increase in AngII and further activation of the AngII/AT1R axis worsening inflammation (discussed below) (Fig. 1) . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) cache = ./cache/cord-324919-ciamusjs.txt txt = ./txt/cord-324919-ciamusjs.txt === reduce.pl bib === id = cord-321624-z2mntwef author = Kowitdamrong, Ekasit title = Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date = 2020-10-09 pages = extension = .txt mime = text/plain words = 3382 sentences = 184 flesch = 57 summary = AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. cache = ./cache/cord-321624-z2mntwef.txt txt = ./txt/cord-321624-z2mntwef.txt === reduce.pl bib === id = cord-327654-9g8zcxaa author = Chi, Xiaojing title = Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain date = 2020-09-10 pages = extension = .txt mime = text/plain words = 4993 sentences = 302 flesch = 51 summary = Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. To determine whether sdAbs targeted different antigenic regions on the SARS-CoV-2 RBD surface, we performed a competition-binding assay using a real-time biosensor (Fig. 3) . Fc fusion sdAbs in culture supernatants were affinity purified with HiTrap Protein A HP antibody purification columns ( Supplementary Fig. 2 ) and analyzed in both reducing and non-reducing conditions in Western blot using an anti-human IgG to detect Fc. As shown in Fig. 4c , the size of the constructed intact sdAb-Fc is around 80 KDa in the non-reducing condition, but a 40 KDa monomer was observed by prior treatment in reducing condition to break disulfide bonds. cache = ./cache/cord-327654-9g8zcxaa.txt txt = ./txt/cord-327654-9g8zcxaa.txt === reduce.pl bib === id = cord-323905-ayufx3wv author = Kort, N. P. title = Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members date = 2020-08-18 pages = extension = .txt mime = text/plain words = 3708 sentences = 225 flesch = 53 summary = title: Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members The April 2020 SARS-CoV-2 survey completed by EHS and EKA members in Europe has confirmed the impact of SARS-CoV-2: this pandemic has resulted in a tremendous reduction in primary hip and knee arthroplasty procedures as shown in the survey. The benefits of hip and knee arthroplasty should be carefully weighed against the risks of viral transmission and infection, complications and mortality in the mostly elderly population requiring joint arthroplasty Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: pre-operative phase 1. Is there a need for -Modification or reorganization of hospital wards (patient density, bed density, medical and nursing stuff density, etc.)?417 (81) 70 (14) Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: post-operative phase 1. cache = ./cache/cord-323905-ayufx3wv.txt txt = ./txt/cord-323905-ayufx3wv.txt === reduce.pl bib === id = cord-322913-sq9mq6f1 author = Ciabattini, Annalisa title = Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population date = 2020-11-06 pages = extension = .txt mime = text/plain words = 8068 sentences = 363 flesch = 33 summary = The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of innate and adaptive immune responses, and the lack of a clear correlate of protection, make the design of vaccination strategies for older people extremely challenging (Fig. 3 ). cache = ./cache/cord-322913-sq9mq6f1.txt txt = ./txt/cord-322913-sq9mq6f1.txt === reduce.pl bib === id = cord-325234-skshcrh1 author = Jin, Tingxu title = SARS-CoV-2 presented in the air of an intensive care unit (ICU) date = 2020-08-15 pages = extension = .txt mime = text/plain words = 4276 sentences = 205 flesch = 54 summary = Therefore, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, it is necessary to 1) determine whether SARS-CoV-2 particles are present in the indoor air and 2) determine whether recovered patients are still shedding virus, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. To date, some studies have reported the presence of SARS-CoV-2 particles in the air in isolation rooms from hospitals treating COVID-19 patients (Yuanfang J,2020; Guo, Wang, Zhang, Li, & Chen,2020; Joshua L. Therefore, our study aims to 1) determine whether SARS-CoV-2 particles are present in the indoor air, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, and 2) determine whether recovered patients are still shedding SARS-CoV-2 particles, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. Our findings revealed the presence of SARS-CoV-2 in the indoor air of the ICU and indicate that the virus may be shed via aerosol for days, even after a patient has tested negative. cache = ./cache/cord-325234-skshcrh1.txt txt = ./txt/cord-325234-skshcrh1.txt === reduce.pl bib === id = cord-325324-kh2aal5n author = Teng, Shaolei title = ACE2 Enhance Viral Infection or Viral Infection Aggravate the Underlying Diseases date = 2020-08-06 pages = extension = .txt mime = text/plain words = 4403 sentences = 274 flesch = 53 summary = SARS-CoV-2 spike protein (S) is cleaved by the human furin enzyme to generate S1, which binds to the host receptor, ACE-2. It is possible that the released free spike or the cleaved S1 protein in the blood might bind to cellular membrane ACE2 of heart, artery and alveolar lung cells to block the conversion of Angiotensin II to Ang-(1-7) and/or Angiotensin I to Ang-(1-9), which is consistent with a previous experimental result on SARS-CoV-1 (59) . Therefore, our hypothesis, as shown in the right side of Fig. 1 as "Viral aggravating existing diseases", is that comorbidities in COVID-19 patients are aggravated by the infection of SARS-CoV-2 to causes higher fatalities because the viral S protein interacts with ACE2 to inhibit ACE2 function. The claims that COVID-19 disproportionately affects the individuals of minority groups and aged people are not only supported by reported data but also by our hypothesis that SARS-CoV-2 infection generates spike protein that interacts with ACE2 to either exhaust ACE2 or inhibit ACE2 function or both so that the comorbidities are aggravated (Figure 1 ). cache = ./cache/cord-325324-kh2aal5n.txt txt = ./txt/cord-325324-kh2aal5n.txt === reduce.pl bib === id = cord-324102-75v4ebag author = Garcia Rodriguez, Alejandro title = SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report date = 2020-10-06 pages = extension = .txt mime = text/plain words = 1728 sentences = 110 flesch = 49 summary = title: SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy. That is the reason why we present a case report of a pregnant woman infected with SARS-COV-2 who showed seizures and sudden blindness. Therefore, we consider that SARS-COV-2 infection during pregnancy could increase the risk of suffering posterior reversible leukoencephalopathy or preeclampsia/eclampsia syndrome. To our knowledge, this is the first report of a patient with COVID-19 presenting preeclampsia associated with eclampsia versus posterior reversible leukoencephalopathy without alarm signs or symptoms. We consider further studies are needed to confirm that SARS-COV-2 infection is a risk factor to develop neurological complications of pregnant woman during pregnancy. cache = ./cache/cord-324102-75v4ebag.txt txt = ./txt/cord-324102-75v4ebag.txt === reduce.pl bib === id = cord-325614-e9hnhzfg author = Todorov, German title = A Possible Path towards Rapid Development of Live-Attenuated SARS-CoV-2 Vaccines: Plunging into the Natural Pool date = 2020-10-14 pages = extension = .txt mime = text/plain words = 3122 sentences = 145 flesch = 41 summary = Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness. The proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, potentially leading to a more rapid cycle of vaccine development, as well as higher vaccine effectiveness. If the candidate attenuated SARS-CoV-2 strain is easily transmissible, we would need to evaluate whether a live-attenuated virus that causes a very mild form of infection but is easy to transmit can be considered sufficiently safe for use as a vaccine, or whether it needs to be further attenuated in the lab, which could slow down the development of the vaccine. All in all, at present there are too many unknowns to predict how much screening of suitable individuals in high-risk subpopulations will be required to find naturally-evolved candidate strains for the development of live-attenuated vaccines. cache = ./cache/cord-325614-e9hnhzfg.txt txt = ./txt/cord-325614-e9hnhzfg.txt === reduce.pl bib === id = cord-327690-di7hfghi author = Yang, Xiaobo title = Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study date = 2020-02-24 pages = extension = .txt mime = text/plain words = 3848 sentences = 241 flesch = 53 summary = title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. In this study, we investigated critically ill patients with confirmed SARS-CoV-2 pneumonia who were admitted to Wuhan Jin Yin-tan hospital. The baseline SARS-CoV-2-associated morbidity and mortality data from this study will be of considerable value for the early identification of individuals who are at risk of becoming critically ill and who are most likely to benefit from intensive care treatment. During the outbreak of SARS-CoV-2 infection, the number of critically ill patients exceeded the capacity of ICUs. Therefore, two provisional ICUs were urgently established in Jin Yin-tan hospital and hence most mechanical ventilator settings and recordings were not recorded, except records of positive end-expiratory pressure in some cases. cache = ./cache/cord-327690-di7hfghi.txt txt = ./txt/cord-327690-di7hfghi.txt === reduce.pl bib === id = cord-325014-n7mnhk2v author = Gujski, Mariusz title = Prevalence of Current and Past SARS-CoV-2 Infections among Police Employees in Poland, June–July 2020 date = 2020-10-11 pages = extension = .txt mime = text/plain words = 4892 sentences = 254 flesch = 49 summary = As the time window for a positive RT-PCR result is short, serological testing, which provides information about whether a person has been exposed to SARS-CoV-2, may be useful for epidemiological purposes to detect the overall burden of previous infection in a given community. The aim of this study was to determine the prevalence of current and past SARS-CoV-2 infections among police employees, a high-risk population due to their professional duties, during the COVID-19 epidemic. Neither sex (p =0.155) nor other variables listed in Figure 2 were significantly associated with the IgG results ( Figure 2 A logistic regression model predicting a positive anti-SARS-CoV-2 IgM+IgA index was developed (Cox and Snell R Square at 0.015 andNagelkerke R Square at 0.033). After including all variables listed in Figures 1 and 2 along with the number of registered cases and deaths due to COVID-19 (per 10,000 inhabitants), only 4 variables showed a correlation with a positive anti-SARS-CoV-2 IgM+IgA index. cache = ./cache/cord-325014-n7mnhk2v.txt txt = ./txt/cord-325014-n7mnhk2v.txt === reduce.pl bib === id = cord-325902-33pxylb3 author = Hemida, Maged Gomaa title = Middle East Respiratory Syndrome Coronavirus and the One Health concept date = 2019-08-22 pages = extension = .txt mime = text/plain words = 6356 sentences = 325 flesch = 58 summary = This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. Experimental MERS-CoV infection in both alpacas and llamas showed a similar pattern to that of dromedary camels (Crameri et al., 2016; Vergara-Alert et al., 2017) , which suggested that both animals might act as a model animal for the study of MERS-CoV in vivo. Very few studies reported the cross-reactivity between MERS-CoV and other coronaviruses such as the bovine coronavirus (BCoV) that might infect dromedary camels. Dromedary camels remain the amplifier of the virus; the close contact of these animals to the human population in certain regions of Africa and Asia may pose a great risk for human infection and indirectly contribute to the spread of the virus. Lack of middle East respiratory syndrome coronavirus transmission from infected camels cache = ./cache/cord-325902-33pxylb3.txt txt = ./txt/cord-325902-33pxylb3.txt === reduce.pl bib === id = cord-326706-75mjs6vm author = Waterfield, Thomas title = Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study date = 2020-11-10 pages = extension = .txt mime = text/plain words = 3573 sentences = 242 flesch = 49 summary = Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. 26 Participants and their parents provided information at enrolment relating to age, sex, previous health and potential predictors of SARS-CoV-2 seropositivity including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/ antibody testing. cache = ./cache/cord-326706-75mjs6vm.txt txt = ./txt/cord-326706-75mjs6vm.txt === reduce.pl bib === id = cord-325966-0g7a9s5z author = Shih, Hsin-I. title = Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines date = 2020-05-30 pages = extension = .txt mime = text/plain words = 7324 sentences = 365 flesch = 39 summary = Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. However, these clinical, laboratory, and imaging findings are nonspecific and cannot differentiate COVID-19 from other viral respiratory infections; viral diagnostic methods specific for SARS-CoV-2 should be applied for disease confirmation. An open-label study published in 2004 suggested, by comparison with a control group that received only ribavirin, that the addition of lopinavir-ritonavir (400 mg and 100 mg, respectively) to ribavirin reduced the risk of adverse clinical outcomes (acute respiratory distress syndrome or death) and viral load among patients with SARS [29] . Some available candidate drugs targeting different levels of human responses to COVID-19, such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, IL-6 blocker and convalescent plasma, may improve the clinical outcomes of critical COVID-19 patients. cache = ./cache/cord-325966-0g7a9s5z.txt txt = ./txt/cord-325966-0g7a9s5z.txt === reduce.pl bib === id = cord-325959-uqg2xkie author = Bundschuh, Christian title = Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma date = 2020-06-08 pages = extension = .txt mime = text/plain words = 2208 sentences = 125 flesch = 57 summary = METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. low "false" positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes Coronavirus Disease 2019 (COVID-19), has recently emerged to cause a human pandemic. For the clinical evaluation we measured SARS-CoV-2 IgM and IgG antibodies in three different cohorts: First in a "positive cohort" of patients with SARS-CoV-2 RT-PCR confirmed 5 COVID-19 with serial blood samples at different time points from symptom onset. Furthermore, the clinical evaluation study demonstrated high "true" positivity rates in the SARS-CoV-2 RT-PCR confirmed COVID-19 patients with symptom onset after 15 days with 94.4% for IgM and 100% for IgG SARS-CoV-2 cache = ./cache/cord-325959-uqg2xkie.txt txt = ./txt/cord-325959-uqg2xkie.txt === reduce.pl bib === id = cord-328175-4i3cz20j author = van Doremalen, Neeltje title = Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets date = 2017-07-31 pages = extension = .txt mime = text/plain words = 5150 sentences = 272 flesch = 51 summary = Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Here we assess the effect of treatment with marmoset-derived hyperimmune plasma as well as the human mAb m336 on disease outcome in the recently developed marmoset MERS-CoV infection model, which recapitulates severe respiratory disease (Falzarano et al., 2014) . Viral loads in lung tissues from hyperimmune plasma-treated compared to control animals were found to be significantly lower using a onetailed unpaired Student's t-test (average of 4.0  10 4 and 1.2  10 6 TCID 50 equivalent/gram, respectively, p-value ¼ 0.008). In this study, hyperimmune plasma treatment of marmosets inoculated with MERS-CoV resulted in a small (0.5e1 log) but significant reduction in respiratory tract viral loads, as well as reduced disease severity such as observed with radiographs, compared to marmosets treated with non-convalescent plasma or PBS. cache = ./cache/cord-328175-4i3cz20j.txt txt = ./txt/cord-328175-4i3cz20j.txt === reduce.pl bib === id = cord-327997-noqbcxua author = Wu, Kevin E. title = RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus date = 2020-06-20 pages = extension = .txt mime = text/plain words = 7201 sentences = 377 flesch = 42 summary = We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. As previously discussed, since much of the APEX-seq mitochondrial data used to train RNA-GPS actually consists of nuclear-encoded transcripts likely picked up as the APEX-COX4 fusion protein is transported to the mitochondria, we hypothesize that our predicted mitochondrial residency is alluding to similarity in localization pathways, rather than localization destination. To further validate the robustness of these results, we also trained a different predictive algorithm (a recurrent neural network, see STAR Methods for additional details) on the APEX-seq data and performed a similar set of experiments, comparing SARS-CoV-2 dominant subcellular residency predictions to human and coronavirus baselines ( Figure S3A /B). cache = ./cache/cord-327997-noqbcxua.txt txt = ./txt/cord-327997-noqbcxua.txt === reduce.pl bib === id = cord-328000-i9tzr13z author = Cockrell, Adam S. title = Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice date = 2018-07-24 pages = extension = .txt mime = text/plain words = 11004 sentences = 519 flesch = 44 summary = Three different strategies were employed for development of SARS-CoV mouse models: (i) different mouse species (or subspecies) were challenged with wildtype human SARS-CoV isolates in order to find a model that allows for replication and reflects severe respiratory disease symptoms observed in infected human patients; (ii) mice were genetically engineered to modify the host receptor, which facilitated productive SARS-CoV replication and pathogenesis; and (iii) adaptive evolution of wild-type SARS-CoV to a chosen mouse species was done to enhance pathogenesis, and associated clinical phenotypes in vivo. To adapt SARS-CoV to cause severe acute respiratory disease in mouse lungs, 6-week-old female BALB/c mice were intra-nasally infected with the clinical Urbani isolate (Roberts et al. Virus infection studies in CC mouse lines, including SARS-CoV, have led to mapping of high and low host response alleles as they relate to development of clinical signs of disease following viral pathogenesis (Bottomly et al. cache = ./cache/cord-328000-i9tzr13z.txt txt = ./txt/cord-328000-i9tzr13z.txt === reduce.pl bib === id = cord-324856-hf969tav author = Abir, Tanvir title = Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys date = 2020-07-21 pages = extension = .txt mime = text/plain words = 4144 sentences = 221 flesch = 53 summary = title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys Since the sheer illness of the whole country is sufficient to destroy the health care system, this current study is to examine changes of individual perception of risk for contracting SARS-Cov-2, and the awareness level in Bangladesh during the early and late lockdowns implemented by the government of Bangladesh. In this study, males who were worried about contracting SARS-Cov-2 were more likely to perceive themselves as being at high risk of contracting the infection, as well as those who did not quarantine themselves or only did so at the request of the public health officers. Moreover, in India, it was found that a higher level of knowledge on COVID-19 was associated with the high-risk perception of contracting the infection during the consistent lockdown period [28] . cache = ./cache/cord-324856-hf969tav.txt txt = ./txt/cord-324856-hf969tav.txt === reduce.pl bib === id = cord-326013-5i35zdmv author = Carpinteiro, Alexander title = Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells date = 2020-10-29 pages = extension = .txt mime = text/plain words = 3113 sentences = 175 flesch = 47 summary = The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection. Pretreatment of the cells with 5, 10, 20, or 25 µM amitriptyline prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike for 30 min (Fig. 3B, Fig. 4A ). Treating Vero cells with neutralizing antibodies to spike or with recombinant ACE2 protein prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike (Fig. 3B, Fig. 4A Amitriptyline and other drugs with similar structure and properties have been clinically used for many years (since 1962) to treat patients with depressive disorder. Best results were obtained with venlafaxin, fluoxetine, escitalopram and mirtazipine, drugs that were also shown in the present study to inhibit acid sphingomyelinase and ceramide release upon pp-VSV-SARS-CoV-2 spike infection. cache = ./cache/cord-326013-5i35zdmv.txt txt = ./txt/cord-326013-5i35zdmv.txt === reduce.pl bib === id = cord-326017-qw4qynqv author = Laskar, Partha title = “Tomorrow Never Dies”: Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies date = 2020-08-06 pages = extension = .txt mime = text/plain words = 14797 sentences = 760 flesch = 42 summary = Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Overall, real-time RT-PCR based method enables developing a high-throughput testing for rapid, on-demand, low-cost, reliable, quantitative detection technique against COVID-19 in clinical settings [39] . Another newly developed method, SARS-CoV-2 DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR), was found to perform simultaneous reverse transcription and isothermal amplification by (i) RT-LAMP for RNA extracted (for nasopharyngeal or oropharyngeal swabs), (ii) Cas12 detection of predefined coronavirus sequences, and (iii) cleavage of a reporter molecule confirms, which detects the virus [56] . cache = ./cache/cord-326017-qw4qynqv.txt txt = ./txt/cord-326017-qw4qynqv.txt === reduce.pl bib === id = cord-329011-spiuqngp author = Huang, Yuan title = Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 date = 2020-08-03 pages = extension = .txt mime = text/plain words = 6045 sentences = 340 flesch = 53 summary = The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. A large number of glycosylated S proteins cover the surface of SARS-CoV-2 and bind to the host cell receptor angiotensinconverting enzyme 2 (ACE2), mediating viral cell entry [8] . The SARS-CoV-2 S protein is highly conserved among all human coronaviruses (HCoVs) and is involved in receptor recognition, viral attachment, and entry into host cells. Structure of the S1 subunit The binding of virus particles to cell receptors on the surface of the host cell is the initiation of virus infection; therefore, receptor recognition is an important determinant of viral entry and a drug design target. Therefore, the development of antibodies targeting this functional motif may cross-bind and neutralize these two viruses and related CoVs. Antiviral peptides prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infection. cache = ./cache/cord-329011-spiuqngp.txt txt = ./txt/cord-329011-spiuqngp.txt === reduce.pl bib === id = cord-328361-hyrke6j2 author = Ithete, Ndapewa Laudika title = Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa date = 2013-10-17 pages = extension = .txt mime = text/plain words = 1186 sentences = 60 flesch = 54 summary = A novel clade 2c betacoronavirus, termed Middle East respiratory syndrome (MERS)-CoV, was recently identified as the causative agent of a severe respiratory disease that is mainly affecting humans on the Arabian Peninsula (1) . Extending on previous work (2), we described European Pipistrellus bat-derived CoVs that are closely related to MERS-CoV (3) . Screening for CoVs was done by nested reverse transcription PCR using broadly reactive oligonucleotide primers targeting a conserved region in the RNA-dependent RNA polymerase (RdRp) gene (online Technical Appendix). PCR amplicons for 4 positive specimens yielded alphacoronavirus sequences related to recently described bat alphacoronaviruses from South Africa (4) . A Bayesian phylogenetic analysis of the 816-nt RdRp sequence confirmed the close relationship between PML/2011 and MERS-CoV (Figure) . Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences cache = ./cache/cord-328361-hyrke6j2.txt txt = ./txt/cord-328361-hyrke6j2.txt === reduce.pl bib === id = cord-331039-qgom2e3n author = Kavitha, Kuppuswamy title = 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4929 sentences = 326 flesch = 57 summary = A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 M(pro) and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. The objectives of this study were i) to identify evolutionarily important active site amino acids by structure-based sequence alignment of SARS-CoV-2 and SARS-CoV M pro enzymes ii) to identify potential non-covalent M pro inhibitors by screening protease-inhibitor-like compounds available in the ZINC database by molecular docking studies iii) prediction of absorption, distribution metabolism, excretion and toxicity properties of the top-scoring inhibitors using in silico methods iv) to validate the stable binding of the lead compounds with SARS-CoV-2 M pro by molecular dynamics (MD) simulations and v) to calculate thermodynamic binding energies for each lead compound -SARS-CoV-2 M pro complex using Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations. cache = ./cache/cord-331039-qgom2e3n.txt txt = ./txt/cord-331039-qgom2e3n.txt === reduce.pl bib === id = cord-331429-mh2hd5fe author = Srikantiah, Padmini title = SARS Clinical Features, United States, 2003 date = 2005-01-17 pages = extension = .txt mime = text/plain words = 1948 sentences = 100 flesch = 48 summary = We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection. Case-patients with laboratory-confirmed SARS were compared to a convenience sample of persons who met the clinical and epidemiologic criteria for suspected or probable SARS but subsequently tested negative for SARS-CoV infection. Controls had negative findings on all testing performed for SARS-CoV, including the absence of antibody against the virus in convalescent-phase serum samples obtained >21 days after onset of symptoms. Over the course of their illness, findings suggestive of a lower respiratory tract infection developed in all 8 patients with laboratory-confirmed SARS; these findings included dyspnea (n = 8), rales (n = 5), and hypoxia (n = 5) (Table 1) . cache = ./cache/cord-331429-mh2hd5fe.txt txt = ./txt/cord-331429-mh2hd5fe.txt === reduce.pl bib === id = cord-328395-2cakgmsj author = Oxford, Alexandra E. title = Endothelial Cell Contributions to COVID-19 date = 2020-09-25 pages = extension = .txt mime = text/plain words = 6707 sentences = 353 flesch = 39 summary = Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. This review will focus on the concept of endothelial cell infection and dysfunction as an active driver of COVID-19, which begins as a respiratory illness, with vascular pathology contributing significantly to the most negative patient outcomes. Endothelial cell infection that proceeds via ACE2 shows how SARS-CoV-2 can replicate into a wide range of cells, which may explain some of the clinical symptoms found in COVID-19 patients. Thus far, we have discussed the viral mechanisms of SARS-CoV-2 and resultant COVID-19 sequelae as they relate to endotheliitis and endothelial cell infection mediated by viral spike protein-ACE2 interaction. The successful use of anti-interleukin drugs to treat the inflammatory symptoms seen in severe COVID-19 would have marked effects on endothelial pathology as these cells are highly responsive to cytokine signaling [59] . cache = ./cache/cord-328395-2cakgmsj.txt txt = ./txt/cord-328395-2cakgmsj.txt === reduce.pl bib === id = cord-324978-9qfhsj3n author = Alagaili, Abdulaziz N. title = Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date = 2014-02-25 pages = extension = .txt mime = text/plain words = 3565 sentences = 165 flesch = 53 summary = The presence of viral nucleic acids in rectal and nasal swabs and a subset of serum and whole blood samples was assayed by reverse transcriptionquantitative PCR (RT-qPCR) with primers targeting the upE and ORF1a genome regions of MERS-CoV (16, 17) . Rectal and nasal swabs collected in parallel with serum samples from the same animals were assayed for MERS-CoV nucleic acids by RT-qPCR. PCR analysis of a random selection of serum and whole blood samples collected from nasal or rectal swab PCR-positive, seropositive, and seronegative DC revealed no evidence of viremia (see Table S1 in the supplemental material). Definitive evidence that DC can be infected with MERS-CoV was obtained when viral sequences were detected in nasal swabs from DC sampled in close proximity to outbreaks of the disease among humans in Qatar (11) and Jeddah, KSA (10) . cache = ./cache/cord-324978-9qfhsj3n.txt txt = ./txt/cord-324978-9qfhsj3n.txt === reduce.pl bib === id = cord-328996-3sf2i45r author = Barthélémy, Romain title = Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome date = 2020-06-06 pages = extension = .txt mime = text/plain words = 1161 sentences = 100 flesch = 59 summary = title: Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome This monocenter retrospective study aimed to evaluate the association between almitrine 19 introduction and improvement of oxygenation in Sars-Cov-2 ARDS. Inclusion criteria in the study were: admission for respiratory failure, a diagnosis of ARDS 24 according to Berlin criteria 8 , laboratory confirmed Sars-Cov-2 infection, almitrine infusion in 25 ICU. In our 73 observational study, almitrine was associated with an increase in PaO 2 /FiO 2 ratio after 74 treatment. Furthermore, despite an associated improvement in PaO 2 /FiO 2 ratio, the majority 76 of patients receiving almitrine went on to needing additional rescue interventions or died. 77 This may be explained by the fact that, in our study, almitrine has been used as a rescue 78 therapy in severe patients with worsening hypoxemia and very low PaO 2 /FiO 2 ratio. cache = ./cache/cord-328996-3sf2i45r.txt txt = ./txt/cord-328996-3sf2i45r.txt === reduce.pl bib === id = cord-329493-ueqlhgn0 author = Stadler, Konrad title = SARS — beginning to understand a new virus date = 2003 pages = extension = .txt mime = text/plain words = 5146 sentences = 248 flesch = 51 summary = A new infectious disease, known as severe acute respiratory syndrome (SARS), appeared in the Guangdong province of southern China in 2002. When Thiel and colleagues 20 isolated one genomic and eight subgenomic RNAs from the FRA strain and sequenced their 5′ ends, they identified a conserved sequence (5′ACGAAC3′) that was located in coronaviruses: S, spike protein; E, envelope protein; M, membrane glycoprotein; and N, nucleocapsid protein. Alternatively, these antigens could be delivered by DNA immunization by Figure 6 | The S1 domain of SARS-CoV spike is structurally related to group 2 coronaviruses. Schematic representation of cysteine positions in the S1 domains of group 1, 2 and 3 coronaviruses, compared with the SARS-CoV spike protein. The complete genome sequence of a SARS-CoV isolate (FRA) and experimental data on its key RNA elements and protein functions are described. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection cache = ./cache/cord-329493-ueqlhgn0.txt txt = ./txt/cord-329493-ueqlhgn0.txt === reduce.pl bib === id = cord-332948-h297ukuu author = Olotu, Fisayo A. title = Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date = 2020-10-16 pages = extension = .txt mime = text/plain words = 5176 sentences = 315 flesch = 51 summary = authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. 30 Identification of other functional (allosteric) sites on the prefusion S protein could present another dynamic and effective approach of preventing SARS-CoV-2 infectivity relative to its interaction with the host cell ACE2 and proteases. 53 Relatively, this study was implemented to (i) identify potential druggable sites across the S1 and S2 domains of the SARS-CoV-2 S protein other than the RBD-hACE2 interface (ii) perform high-throughput (virtual) screening of ~1500 FDA approved drugs against the most druggable site(s) (iii) investigate the binding dynamics and interaction mechanisms of the compounds and their consequential effects on the S-protein RBD-ACE2 complex. We believe this systematic study will be able to provide structural and molecular insights into possible allosteric sites on SARS-CoV-2 S protein suitable for selective targeting and structureComputational methodologies cache = ./cache/cord-332948-h297ukuu.txt txt = ./txt/cord-332948-h297ukuu.txt === reduce.pl bib === id = cord-327063-ea7a1xfl author = Dhama, Kuldeep title = SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus date = 2020-08-02 pages = extension = .txt mime = text/plain words = 11048 sentences = 600 flesch = 48 summary = The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARSand MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease. Further research exploring the SARS-CoV-2 associated zoonosis and mechanisms accounting for its initial transmission from animals to humans, will lead to sort out the spread of this virus as well as design and develop appropriate prevention and control strategies to counter COVID-19. The present comprehensive manuscript presents an overview on COVID-19, an emerging SARS-CoV-2 infectious disease while focusing mainly on the events and circumstantial evidences with regards to this virus jumping the species barriers, sharing a few lessons learned from SARS-and MERS-CoVs, zoonotic spillover events (zoonosis), acquiring transmission ability to infect humans, and adopting appropriate preventive and control measures [42] . cache = ./cache/cord-327063-ea7a1xfl.txt txt = ./txt/cord-327063-ea7a1xfl.txt === reduce.pl bib === id = cord-329010-n0mz098o author = McKee, Dwight L. title = Candidate drugs against SARS-CoV-2 and COVID-19 date = 2020-04-29 pages = extension = .txt mime = text/plain words = 5193 sentences = 260 flesch = 41 summary = Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. Drugs that have recently been shown to target MERS-CoV in mice [15] , and to inhibit Ebola virus RdRP and SARS-CoV-2 proteases in humans, such as remdesivir and ritonavir/lopinavir, also constitute candidate drugs against SARS-CoV-2 and are now investigated for their therapeutic efficacy in COVID-19 patients in 2 international clinical trials (SOLIDARITY Trial and DisCoVeRy Trial). The emergence of the novel beta coronavirus SARS-CoV-2 from Wuhan, Hubei province, China in December 2019 rapidly led to a pandemic involving more than 2,500,000 infected persons and more proven drugs such as camostat mesilate which prevents virus host cell entry by inhibiting TMPRSS2 [8] , and chloroquine phosphate which inhibits terminal phosphorylation of ACE2, or hydroxychloroquine which is metabolized in vivo to chloroquine [44] . cache = ./cache/cord-329010-n0mz098o.txt txt = ./txt/cord-329010-n0mz098o.txt === reduce.pl bib === id = cord-330343-p7a8chn4 author = Kelly-Cirino, Cassandra title = An updated roadmap for MERS-CoV research and product development: focus on diagnostics date = 2019-02-01 pages = extension = .txt mime = text/plain words = 5812 sentences = 274 flesch = 40 summary = ► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. cache = ./cache/cord-330343-p7a8chn4.txt txt = ./txt/cord-330343-p7a8chn4.txt === reduce.pl bib === id = cord-328289-3h3kmjlz author = Iadecola, Costantino title = Effects of COVID-19 on the nervous system date = 2020-08-19 pages = extension = .txt mime = text/plain words = 6524 sentences = 349 flesch = 40 summary = Another Parkinson's disease patient with obesity, hypertension and diabetes, exhibited at autopsy, in addition to hypoxic-ischemic neuronal damage, microhemorrhages, white matter lesions and enlarged perivascular spaces, but no evidence of SARS-CoV-2 in the brain (Kantonen et al., 2020) . The encephalopathy is most likely a consequence of systemic factors, such as cytokine sickness, hypoxia and metabolic dysfunction due to peripheral organ failure, while the strokes seem to be related more to hypercoagulability and endothelial injury than to SARS-CoV-2 vasculitis affecting brain vessels. In some cases, the possibility of a SARS-CoV-2 encephalitis could not be ruled out based on the potential for the virus to infect neurons (Song et al., 2020) , but definitive clinical and pathological evidence of neurotropism is lacking. cache = ./cache/cord-328289-3h3kmjlz.txt txt = ./txt/cord-328289-3h3kmjlz.txt === reduce.pl bib === id = cord-332595-874tpi09 author = Salehi, Najmeh title = Profiling of Initial Available SARS-CoV-2 Sequences from Iranian Related COVID-19 Patients date = 2020-09-08 pages = extension = .txt mime = text/plain words = 1800 sentences = 111 flesch = 61 summary = To this purpose, SARS-CoV-2 full genome sequence profiling of 20 patients in Iran and different countries that already had a travel history to Iran or contacts with Iranian cases were provided from the GISAID database. The bioinformatics analysis showed 44 different nucleotide mutations that caused 26 nonsynonymous mutations in protein sequences with regard to the reference full genome of the SARS-CoV-2 sequence (NC_045512.2). On the other hand, nineteen sequences of the full genome sequence of SARS-CoV-2 on the GISAID database from patients in different countries that had a travel history to Iran or contacts with Iranian cases were retrieved from the database. In this study, the full genome sequences of SARS-CoV-2 from the 20 Iranian related COVID-19 patients were profiled in detail. B. The nucleotide and protein mutations, the number of mutation events in data from the 20 Iranian related patients, the entropy values of these mutations in all 3927 SARS-CoV-2 sequences, and the corresponded proteins are depicted. cache = ./cache/cord-332595-874tpi09.txt txt = ./txt/cord-332595-874tpi09.txt === reduce.pl bib === id = cord-328003-yovp8squ author = Duan, Liangwei title = The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date = 2020-10-07 pages = extension = .txt mime = text/plain words = 7346 sentences = 386 flesch = 46 summary = Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. cache = ./cache/cord-328003-yovp8squ.txt txt = ./txt/cord-328003-yovp8squ.txt === reduce.pl bib === id = cord-330597-nftwj0d5 author = Hopfer, Helmut title = Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues date = 2020-09-27 pages = extension = .txt mime = text/plain words = 4636 sentences = 328 flesch = 48 summary = Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. To better understand the ultrastructural morphology of SARS-CoV-2 infection and COVID-19, we will first briefly discuss the pathogenesis of COVID-19 and coronavirus replication in general and then examine the TEM findings in more detail. All rights reserved Coronaviruses including SARS-CoV-2 and the morphological changes associated with replication can be visualised by TEM in infected cell lines (figure 3A-G) [81] [82] [83] [84] [85] 87, 88] or organoids [96, 97] . Based on the cell culture findings outlined above, we expect to find the same SARS-CoV-2 morphology and distribution in vesicles of autopsy and biopsy tissues of COVID-19 patients. cache = ./cache/cord-330597-nftwj0d5.txt txt = ./txt/cord-330597-nftwj0d5.txt === reduce.pl bib === id = cord-331472-kd4uxcve author = Shahid, Zainab title = COVID‐19 and Older Adults: What We Know date = 2020-04-20 pages = extension = .txt mime = text/plain words = 2314 sentences = 153 flesch = 53 summary = Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). 5 The Centers for Disease Control and Prevention (CDC) reported that although individuals older than age 65 comprise 17% of the total population in the United States, they make up 31% of COVID-19 infections, 45% of hospitalizations, 53% of intensive care unit admissions, and 80% of deaths caused by this infection. 15, 16 These symptoms are also common in older adults; one study on 21 critically ill patients with SARS-CoV-2 infection, with a mean age of 70 years, found that the most common presenting symptoms were shortness of breath (76%), fever (52%), and cough (48%). 19 One study on 46 fatal cases of SARS-CoV-2, in which 84% of patients were older than age 60, found that diabetes is likely associated with increased mortality. cache = ./cache/cord-331472-kd4uxcve.txt txt = ./txt/cord-331472-kd4uxcve.txt === reduce.pl bib === id = cord-332080-923jpec0 author = Lai, Chih-Cheng title = In vitro diagnostics of coronavirus disease 2019: technologies and application date = 2020-06-05 pages = extension = .txt mime = text/plain words = 1189 sentences = 92 flesch = 58 summary = Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. (Hangzhou Bigfish Bio-tech Co., Ltd., Zhejiang, China) was recently registered 127 as a CE-IVD for detecting SARS-CoV-2 ORF-1ab and N genes in 128 nasopharyngeal swabs, sputum, and BAL fluids. The 145 performance of the Xpress SARS-CoV-2 test was clinically evaluated in 146 patients with respiratory illnesses from whom contrived nasopharyngeal swab 147 samples were collected into viral transport media. Serological tests that can detect SARS-CoV-2 IgG-IgM antibodies are simpler 248 than rRT-PCR, and do not require complicated equipment and protocols 249 (Table 3) . During the previous SARS 251 epidemic, the IgM antibody was the first line of defense during viral infections 252 and was detectable in blood samples from patients after 3 -6 days. Dynamics of 617 anti-SARS-Cov-2 IgM and IgG antibodies among COVID-19 patients cache = ./cache/cord-332080-923jpec0.txt txt = ./txt/cord-332080-923jpec0.txt === reduce.pl bib === id = cord-332448-5fz8ef4f author = Mutnal, M. B. title = Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses date = 2020-05-02 pages = extension = .txt mime = text/plain words = 2583 sentences = 159 flesch = 55 summary = Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. . https://doi.org/10.1101/2020.04.30.20086116 doi: medRxiv preprint of this study is to encourage other laboratories to consider an early start to testing during pandemics, share 74 initial trends in this part of the world and possible impact of SARS-CoV-2 on other seasonal respiratory 75 This report describes the early trends of SARS-CoV-2 infections in the central and north Texas, 76 USA and impact of epidemiological interventions that may have led to the decrease in the incidence of was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. BSWH laboratory provided test results data on both ambulatory and inpatient 275 population, and shared patient demographics with local public health officials. cache = ./cache/cord-332448-5fz8ef4f.txt txt = ./txt/cord-332448-5fz8ef4f.txt === reduce.pl bib === id = cord-332778-rf47ptj6 author = Vivarelli, Silvia title = Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial? date = 2020-08-10 pages = extension = .txt mime = text/plain words = 7447 sentences = 374 flesch = 44 summary = It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. Given their immune-compromised status, cancer patients infected by SARS-CoV-2 might be at a higher risk of developing severe and critical consequences upon COVID-19, including ARDS, septic shock and acute myocardial infarction [29] [30] [31] . Nevertheless, cancer patients, when infected by SARS-CoV-2 might develop more severe outcomes, if anti-cancer treatments induce a weakening of the host immune health [38] . Since the beginning of this pandemic, nine independent clinical studies have been published about the risks possibly related to SARS-CoV-2 infection in patients with cancer. In line with this concept, three additional independent clinical studies are currently enrolling non-cancer COVID-19 patients to test the efficacy of administering ICIs to reshape the impaired immune system of SARS-CoV-2 infected individuals (i.e., NCT04268537; NCT04356508 and NCT04413838). cache = ./cache/cord-332778-rf47ptj6.txt txt = ./txt/cord-332778-rf47ptj6.txt === reduce.pl bib === id = cord-331193-33cyvidx author = Mawhinney, Jamie A title = Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode date = 2020-06-14 pages = extension = .txt mime = text/plain words = 2512 sentences = 161 flesch = 50 summary = Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. [9] [10] [11] [12] This article outlines a case of COVID-19 presenting with an acute manic episode necessitating emergency intubation and discusses potential mechanisms for the development of neuropsychiatric disease. ► The neuroinvasive potential of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (neurotropism) has been reported, but the pathophysiology remains unclear with uncertainty over its long-term consequences. cache = ./cache/cord-331193-33cyvidx.txt txt = ./txt/cord-331193-33cyvidx.txt === reduce.pl bib === id = cord-331856-j0gedx43 author = Basile, K. title = Accuracy amidst ambiguity: false positive SARS-CoV-2 nucleic acid tests when COVID-19 prevalence is low date = 2020-09-30 pages = extension = .txt mime = text/plain words = 1238 sentences = 69 flesch = 45 summary = In countries with a low prevalence of COVID-19 and a low pre-test probability, confirmation of positive nucleic acid test (NAT) results for SARS-CoV-2 is recommended given the potential for false positive results. [2] [3] [4] Initially, the Public Health Laboratory Network (PHLN) Australia recommended that confirmatory testing be performed on samples where SARS-CoV-2 RNA had been detected to ensure that the result was a true positive. In the context of Australia's low prevalence of COVID-19 and thus low pre-test probability for infection, we recommend that all positive SARS-CoV-2 NAT results be confirmed by supplementary testing on the original nucleic acid extract and/or re-extraction of nucleic acid from the original sample (if available) and tested using another assay(s) with different gene targets and/or lower limits of detection 10 (Fig. 1) . cache = ./cache/cord-331856-j0gedx43.txt txt = ./txt/cord-331856-j0gedx43.txt === reduce.pl bib === id = cord-333326-n9ifhw5s author = Wardell, Hanna title = Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates date = 2020-07-09 pages = extension = .txt mime = text/plain words = 2919 sentences = 173 flesch = 44 summary = Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Herein we present a case series of 4 full-term neonates who were hospitalized with fever and found to be infected with SARS-CoV-2. Due to the concern for end-organ involvement with possibly evolving acute myocardial injury as well as a supplemental oxygen requirement, the patient was initiated on therapy with remdesivir on inpatient day 4 via an expanded-access program from the manufacturer after approval from the US Food and Drug Administration and local institutional review board, with informed consent. In this report, we present 4 febrile neonates hospitalized with SARS-CoV-2 infection with favorable outcomes. SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress cache = ./cache/cord-333326-n9ifhw5s.txt txt = ./txt/cord-333326-n9ifhw5s.txt === reduce.pl bib === id = cord-332723-rz1iilsv author = Creager, Hannah M. title = Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2 date = 2020-07-06 pages = extension = .txt mime = text/plain words = 1474 sentences = 114 flesch = 60 summary = Since 30% of nasopharyngeal swab specimens have a SARS CoV-2 Ct >30 and thus detection of virus in low titers is clinically relevant, a sample with a high titer was diluted and each 10 fold dilution was tested in triplicate and compared against 6 other EUA approved SARS CoV-2 assays. These data suggested that the BioFire® RP2.1 panel, along with four other SARS CoV-2 assays (Roche cobas, Cepheid Xpert Xpress, BioFire® Defense COVID19, and NECoV19), consistently detected viral RNA at the 10-7 dilution. Ten-fold serial dilutions of a natural nasopharyngeal swab specimen with known high positivity for SARS-CoV-2 RNA (E gene detected at a cycle threshold (Ct) of 16.6 by the cobas SARS-CoV-2 assay) were prepared with a diluent of pooled NPS. Comparison of SARS-CoV-2 Detection from Nasopharyngeal Swab Samples by the Roche cobas(R) 6800 SARS-CoV-2 Test and a Laboratory-Developed Real-Time RT-PCR test cache = ./cache/cord-332723-rz1iilsv.txt txt = ./txt/cord-332723-rz1iilsv.txt === reduce.pl bib === id = cord-333547-88dkh6xd author = Hasan, Shadi W. title = Detection and Quantification of SARS-CoV-2 RNA in Wastewater and Treated Effluents: Surveillance of COVID-19 Epidemic in the United Arab Emirates date = 2020-10-19 pages = extension = .txt mime = text/plain words = 3980 sentences = 220 flesch = 54 summary = Testing SARS-CoV-2 viral loads in wastewater has recently emerged as a method of tracking the prevalence of the virus and an early-warning tool for predicting outbreaks in the future. A limited number of studies have shown that the shedding period of SARS-CoV-2 in stool samples varies considerably, and can still be detected up to 27.9 ± 10.7 days after infection in some cases [9, 11] . Consequently, the main objectives of this study were: (i) to detect the presence of SARS-CoV-2 virus in municipal (untreated) wastewater and treated effluents of wastewater treatment plants (WWTPs) in the UAE; (ii) to quantify the viral concentration in viral gene copies per liter; and (iii) to explore whether these measurements mirror infections in the population in order to comment on the utility of this method to track the epidemiology of the disease. cache = ./cache/cord-333547-88dkh6xd.txt txt = ./txt/cord-333547-88dkh6xd.txt === reduce.pl bib === id = cord-333682-ktbnrkwh author = Dong, Yunzhu title = Antibodies in the breast milk of a maternal woman with COVID-19 date = 2020-07-03 pages = extension = .txt mime = text/plain words = 1332 sentences = 82 flesch = 58 summary = A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Although clinical and laboratory characteristics, and outcomes of pregnant women with COVID-19 have been reported [4], there are no continuously monitored data about the viral loads in several body fluids of the maternal women that would bring potential risks of SARS-CoV-2 infection to neonates [8] . The titers of IgG antibody in breast milk were 2.34, 3.02, 2.84, 2.79, and 3.35, respectively, when three SARS-CoV-2 negative maternal woman's breast milk were tested as control (mean titer 0.98) (Figure 1, panel D) . (D) Titers of IgG antibody to SARS-CoV-2 in maternal woman's breast milk determined using ELISA. cache = ./cache/cord-333682-ktbnrkwh.txt txt = ./txt/cord-333682-ktbnrkwh.txt === reduce.pl bib === id = cord-332992-8rmqg4rf author = de Vries, A. A. F. title = SARS-CoV-2/COVID-19: a primer for cardiologists date = 2020-07-15 pages = extension = .txt mime = text/plain words = 9182 sentences = 433 flesch = 39 summary = Although SARS-CoV-2 particles/components have been detected in, for example, endothelial cells, the digestive tract and the liver, not all extrarespiratory manifestations of COVID-19 are necessarily caused by direct viral injury but may also be the consequence of the hypoxaemia, (hyper)inflammatory response, neuroendocrine imbalance and other pathophysiological changes induced by the airway infection [43] . Factors that may contribute to the thrombophilia observed in severely ill COVID-19 patients include the following: (1) a disturbed balance between pro-and anticoagulant activities due to excessive production of proinflammatory cytokines, activation of complement, formation of neutrophil extracellular traps and activation of platelets; (2) inflammation-related endothelial activation; (3) death of SARS-CoV-2-infected endothelial cells; (4) endothelial dysfunction caused by unbalanced angiotensin IIangiotensin II type-1 receptor signalling; (5) formation of prothrombotic antiphospholipid antibodies; (6) immobility-associated reduction of blood flow; (7) hypoxia due to respiratory impairment resulting from SARS-CoV-2-induced lung injury [79] [80] [81] . cache = ./cache/cord-332992-8rmqg4rf.txt txt = ./txt/cord-332992-8rmqg4rf.txt === reduce.pl bib === id = cord-333703-1ku3jc9s author = Kraus, Aurora title = A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date = 2020-11-08 pages = extension = .txt mime = text/plain words = 8452 sentences = 605 flesch = 57 summary = Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. In mice and humans, ace2 expression is detected in 121 sustentacular cells, olfactory stem cells known as horizontal and globose basal cells in the 122 olfactory epithelium, and vascular cells (pericytes) in the olfactory bulb (Brann et al., 2020 The present study reports for the first time that zebrafish larvae exposed to SARS-CoV-2 appear 134 to mount innate immune responses that resemble cytokine responses of mild COVID-19 patients. There are copious amounts of immune cells in the teleost olfactory organ ( Intranasal delivery of SARS-CoV-2 S RBD induces inflammatory responses and 318 widespread loss of olfactory receptor expression in adult zebrafish olfactory organ 319 320 cache = ./cache/cord-333703-1ku3jc9s.txt txt = ./txt/cord-333703-1ku3jc9s.txt === reduce.pl bib === id = cord-334220-sqvfr31q author = Messina, Francesco title = Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date = 2020-11-03 pages = extension = .txt mime = text/plain words = 4218 sentences = 237 flesch = 44 summary = The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. cache = ./cache/cord-334220-sqvfr31q.txt txt = ./txt/cord-334220-sqvfr31q.txt === reduce.pl bib === id = cord-335155-x9az3twa author = Qi, Zhen title = Phylogeny of SARS-CoV as inferred from complete genome comparison date = 2003 pages = extension = .txt mime = text/plain words = 1616 sentences = 97 flesch = 59 summary = SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. To date, genomes from 12 SARS-CoV isolates and 12 previously identified coronaviruses have been completely sequenced. The unrooted phylogenetic tree was constructed for genomes from 12 SARS-CoV isolates and that from 12 previously identified coronviruses (Fig. 1) . Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJOI) cache = ./cache/cord-335155-x9az3twa.txt txt = ./txt/cord-335155-x9az3twa.txt === reduce.pl bib === id = cord-334550-xb0alubj author = Samaddar, Arghadip title = The Enigma of Low COVID-19 Fatality Rate in India date = 2020-07-28 pages = extension = .txt mime = text/plain words = 6405 sentences = 367 flesch = 48 summary = These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. Researchers from Translational Bioinformatics Group at International Center for Genetic Engineering and Biotechnology (ICGEB) in collaboration with the Department of Biochemistry, Jamia Hamdard, New Delhi, India, performed an integrated mutational analysis of SARS-CoV-2 genomes from different geographical locations, including India, Italy, United States, Nepal and Wuhan, and observed a novel mutation in S protein (A930V, 24351C>T) of the Indian strain, which was absent in other strains (Sardar et al., 2020) . While this apparent protection among Indians is largely attributed to non-heritable influences as discussed earlier, a safe and effective vaccine against SARS-CoV-2 can reduce disease severity, control transmission, and prevent future infections across all populations. cache = ./cache/cord-334550-xb0alubj.txt txt = ./txt/cord-334550-xb0alubj.txt === reduce.pl bib === id = cord-334313-v2syspu6 author = Long, S. Wesley title = Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date = 2020-05-03 pages = extension = .txt mime = text/plain words = 4525 sentences = 251 flesch = 48 summary = We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. Because in vitro resistance of SARS-CoV to remdesivir has been reported to be caused by either of two amino acid replacements in RdRp (Phe476Leu and Val553Leu), we interrogated our data for polymorphisms in the nsp12 gene. cache = ./cache/cord-334313-v2syspu6.txt txt = ./txt/cord-334313-v2syspu6.txt === reduce.pl bib === id = cord-333498-d25qfq0f author = Chitranshi, Nitin title = Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates date = 2020-07-09 pages = extension = .txt mime = text/plain words = 5999 sentences = 378 flesch = 51 summary = Recent release of the high-resolution crystal structure for the main proteinase 3CL pro (Protein Data Bank, PDB ID: 6Y2G), describing an additional amide bond with the α-ketoamide inhibitor pyridone ring to enhance the half-life of the compound in plasma [16] is suggested to accelerate the targeted drug discovery efforts. Since the initial stages of the SARS-CoV-2 outbreak, laboratories and hospitals around the world have sequenced viral genome data with unprecedented speed, enabling real-time understanding of this novel disease process, which will hopefully contribute to the development of novel candidate drugs. In contrast, our docking studies revealed that bilobetin, predicted almost comparable binding energy with that of amentaflavone (− 8.29 kcal/mol) suggesting that mutation in SARS-CoV-2 3CL pro could potentially disrupt hydrogen bonding or induce some conformational change that could result in alterations in the binding site thus affecting inhibitor interactions with the enzyme active site residues. cache = ./cache/cord-333498-d25qfq0f.txt txt = ./txt/cord-333498-d25qfq0f.txt === reduce.pl bib === id = cord-329190-kv9n2qj3 author = Rabaan, Ali A. title = A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date = 2017-09-01 pages = extension = .txt mime = text/plain words = 8886 sentences = 433 flesch = 44 summary = The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including 'Middle East respiratory syndrome coronavirus', 'MERS-CoV', 'SARS', 'therapy', 'molecular', 'vaccine', 'prophylactic', 'S protein', 'DPP4', 'heptad repeat', 'protease', 'inhibitor', 'anti-viral', 'broad-spectrum', 'interferon', 'convalescent plasma', 'lopinavir ritonavir', 'antibodies', 'antiviral peptides' and 'live attenuated viruses'. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] . cache = ./cache/cord-329190-kv9n2qj3.txt txt = ./txt/cord-329190-kv9n2qj3.txt === reduce.pl bib === id = cord-334564-bqh9jkds author = Raony, Ícaro title = Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date = 2020-05-27 pages = extension = .txt mime = text/plain words = 9893 sentences = 464 flesch = 41 summary = Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) . cache = ./cache/cord-334564-bqh9jkds.txt txt = ./txt/cord-334564-bqh9jkds.txt === reduce.pl bib === id = cord-334773-yw2qgv13 author = Lisco, Giuseppe title = Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review date = 2020-08-10 pages = extension = .txt mime = text/plain words = 7901 sentences = 359 flesch = 32 summary = This concern has been further confirmed by the results of a cohort study among 85 fatal cases of COVID-19 in Wuhan, hence defining DM as a potentially harmful comorbidity predisposing to worse clinical course or death once SARS-CoV-2 infection occurred [49] . Different hypothesis should be considered for explaining this clinical phenomenon, including glucose control at baseline and during the infection course, pathophysiology and immune system response in SARS-CoV-2 infected patients with T2D, diabetes-related comorbidities and concomitant medications. In conclusion, diabetic patients especially elderly individuals and those with worse baseline glucose control may exhibit immune system dysregulation that predispose them to a less effective response against SARS-CoV-2 and to a dysfunctional inflammation that requires to be carefully monitored in confirmed cases of COVID-19, for preventing or avoiding a harmful progression of the disease. Immune response and systemic inflammation play a crucial role in SARS-CoV-2 infection, particularly in case of severe clinical course of the disease. cache = ./cache/cord-334773-yw2qgv13.txt txt = ./txt/cord-334773-yw2qgv13.txt === reduce.pl bib === id = cord-331094-22366b81 author = Ianevski, Aleksandr title = Potential Antiviral Options against SARS-CoV-2 Infection date = 2020-06-13 pages = extension = .txt mime = text/plain words = 6822 sentences = 424 flesch = 49 summary = We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs. cache = ./cache/cord-331094-22366b81.txt txt = ./txt/cord-331094-22366b81.txt === reduce.pl bib === id = cord-335289-m4u96x2v author = Bhattacharya, Manojit title = Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach date = 2020-03-05 pages = extension = .txt mime = text/plain words = 1017 sentences = 81 flesch = 49 summary = authors: Bhattacharya, Manojit; Sharma, Ashish R.; Patra, Prasanta; Ghosh, Pratik; Sharma, Garima; Patra, Bidhan C.; Lee, Sang‐Soo; Chakraborty, Chiranjib title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach Therefore, as the situation was getting worse and worse, the need for designing a suitable peptide vaccine component against the SARS-COV-2 was growing. The amino acid sequence of the targeted protein on SARS-COV-2 was collected from the National Centre for Biotechnological Information (NCBI) database. We obtained a total of 34 sequential linear B-cell epitopes of varying lengths from the IEDB server within spike glycoprotein of SARS-COV-2. In this study, we linked the 13 MHC-I and 3 MHC-II antigenic epitopes with (EAAAK) 3 linker peptide to construct a vaccine component. Moreover, the molecular docking of vaccine components with the TLR-5 proves the significance and effectiveness of these epitopes as an ideal vaccine candidate against SARS-COV-2. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach cache = ./cache/cord-335289-m4u96x2v.txt txt = ./txt/cord-335289-m4u96x2v.txt === reduce.pl bib === id = cord-336057-tj9qcuf8 author = Lv, Yantian title = No intrauterine vertical transmission in pregnancy with COVID-19: a case report date = 2020-08-05 pages = extension = .txt mime = text/plain words = 1338 sentences = 88 flesch = 59 summary = The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. Amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were collected during the operation and tested for the SARS-COV-2 nucleic acid, and the mother and infant were separated after the operation. In addition, not only SARS-COV-2 nucleic acid test results were negative in 4 times pharyngeal swabs, but also the anal swab, amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were negative. Li 9 also reported a 35-week pregnant woman with COVID-19, whose amniotic fluid, cord blood and placenta, breast milk samples as well as neonates swab SARS-COV-2 nucleic acid were all negative. cache = ./cache/cord-336057-tj9qcuf8.txt txt = ./txt/cord-336057-tj9qcuf8.txt === reduce.pl bib === id = cord-337105-jlmh79qv author = Jacob, Fadi title = Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium date = 2020-09-21 pages = extension = .txt mime = text/plain words = 9954 sentences = 567 flesch = 53 summary = We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. QPCR analysis also showed higher levels of ACE2 and TMPRSS2 expression in CPOs at 50 DIV and 100 DIV than in hippocampal organoids ( Figure S2D ) Together, these results show that our CPOs exhibit a similar transcriptome as adult human choroid plexus tissue and express markers for choroid plexus epithelial cells and SARS-CoV-2 receptors, representing a suitable experimental model to study SARS-CoV-2 infection. Our finding that dysregulated gene expression varies widely among hepatocyte, intestinal, and choroid plexus organoids infected with SARS-CoV-2 suggests unique responses in different cell types and highlights the need for diverse human cellular model systems when studying the disease. cache = ./cache/cord-337105-jlmh79qv.txt txt = ./txt/cord-337105-jlmh79qv.txt === reduce.pl bib === id = cord-334976-53cd16w5 author = Jo, Seri title = Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro date = 2020-08-04 pages = extension = .txt mime = text/plain words = 3659 sentences = 222 flesch = 55 summary = An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. The proteolytic assay using SARS-CoV-2 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The compound showed the severely reduced fluorescent intensity and thus represented their SARS-CoV-2 3CLpro inhibitory activity. Among them, baicalin, herbacetin and pectolinarin revealed the prominent inhibitory activity against SARS-CoV-2 3CLpro. The binding modes of herbacetin and pectolinarin were similar to those obtained from the docking study of the catalytic domain of SARS-CoV 3CLpro 21 . In the previous results of SARS-CoV 3CLpro 21 , only the three effect flavonoids (herbacetin, pectolinarin, and rhoifolin) were mentioned. cache = ./cache/cord-334976-53cd16w5.txt txt = ./txt/cord-334976-53cd16w5.txt === reduce.pl bib === id = cord-335122-8s3bcyo8 author = Marshall, Steve title = COVID-19: What do we know? date = 2020-09-21 pages = extension = .txt mime = text/plain words = 5249 sentences = 375 flesch = 41 summary = 44, 45, [47] [48] [49] The amount of viable SARS-CoV-2 in droplet nuclei remains unclear, but in subjects infected with other respiratory viruses, such as influenza, experiments comparing coughing and breathing suggest an equivalent production of viral RNA and replication-competent virus, detected at close range (< 12 inches). 78 In situations where healthcare workers wearing personal protective equipment (PPE) attend to patients with COVID-19 and do not perform medical AGPs, direct airborne transmission of replicationcompetent SARS-CoV-2 has not been confirmed. 79 The results of hospital studies evaluating aerosolization of body fluids and respiratory droplets of SARS-CoV-1 infected patients generated during certain medical AGPs (tracheal intubation, non-invasive ventilation, bronchoscopy, etc.), suggest that airborne transmission of SARS-CoV-2 may be possible during these procedures. Currently there are no studies reporting airborne viable (replication-competent) SARS-CoV-2 virus J o u r n a l P r e -p r o o f in hospital settings where infected patients are cared for, but not subjected to medical AGPs, by healthcare workers wearing surgical masks. cache = ./cache/cord-335122-8s3bcyo8.txt txt = ./txt/cord-335122-8s3bcyo8.txt === reduce.pl bib === id = cord-337835-78i6j11i author = Alfaraj, Sarah H. title = The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus date = 2017-02-09 pages = extension = .txt mime = text/plain words = 1534 sentences = 115 flesch = 62 summary = title: The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus 1 We present four cases of combined infection with influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A repeat swab after 3 days was negative for MERS-CoV but positive for influenza A. The NLST worked with the FES teams in the North West (NW) and West Midlands (WMids) regions of England to audit the reporting of Legionella cases with onset dates during each calendar year between 2012 and 2014, inclusive. WHO guidelines for investigation of cases of human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) cache = ./cache/cord-337835-78i6j11i.txt txt = ./txt/cord-337835-78i6j11i.txt === reduce.pl bib === id = cord-336150-l8w7xk0b author = Rathore, Jitendra Singh title = Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: an overview date = 2020-08-25 pages = extension = .txt mime = text/plain words = 7362 sentences = 399 flesch = 54 summary = The essential surface glycoprotein of SARS-CoV-2 known as spike (S) protein, essential for host cell receptor binding, showed only 72% similarity with SARS-CoV at the nucleotide level. Comparative genome analysis of RaTG13, a virus from a Rhinolophusaffinis (i.e. horseshoe) bat sampled from Yunnan province in China in 2013, with SARS-CoV-2, showed that SARS-CoV-2 has 96% similarity at the nucleotide sequence level . Later, it was found that the disease was caused by a virus designated as a novel human coronavirus, MERS-CoV, phylogenetic data showed that it belonged to lineage C of the Betacoronavirusgenus and was highly similar to bat coronaviruses HKU4 (Tylonycterispachypus) and HKU5 (Pipistrelluspipistrellus; Lau et al. When cell lines over-expressed the transmembrane protein 'angiotensin-converting enzyme 2' (ACE2) from humans, bats, pig or civet cats and were infected with SARS-CoV-2, results showed that they became hypersensitized to infection, thus indicating that ACE2 is a SARS-CoV-2 receptor . Recently, neutralizing monoclonal antibodies and nanobodies against the RBD domain of S protein showed protection against SARS-CoV and MERS-CoV (Du et al. cache = ./cache/cord-336150-l8w7xk0b.txt txt = ./txt/cord-336150-l8w7xk0b.txt === reduce.pl bib === id = cord-337089-ksh62ni0 author = Salajegheh Tazerji, Sina title = Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review date = 2020-09-21 pages = extension = .txt mime = text/plain words = 4901 sentences = 293 flesch = 53 summary = In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. However, based on recently published findings, other authors hypothesized that an immunological cross-protection between SARS-CoV-2 and canine respiratory coronavirus (CRCoV) exists due to the high homology between the spike protein epitopes of the two taxonomicallyrelated coronaviruses [21] . The objective of the present study was to gather, present, and discuss information on the reported cases of COVID-19 in animals focusing on the virus transmission cases in pets and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. cache = ./cache/cord-337089-ksh62ni0.txt txt = ./txt/cord-337089-ksh62ni0.txt === reduce.pl bib === id = cord-337712-ylqgraos author = Heinz, Franz X. title = Profile of SARS-CoV-2 date = 2020-10-30 pages = extension = .txt mime = text/plain words = 6028 sentences = 301 flesch = 44 summary = Despite these similarities, distinguishing features were identified that are likely to contribute to the biological differences observed between the two viruses, including the significantly higher rate of subclinical and mild infections caused by SARS-CoV-2, which makes control of virus spread currently so difficult. If expectations were too optimistic and results obtained with some of the front runners are disappointing, windows of opportunity will open for an arsenal of alternative developments in progress [54, 59] (https:// www.who.int/publications/m/item/draft-landscapeof-covid-19-candidate-vaccines, accessed 2 October 2020) These include subunit vaccines with S proteins stabilized in their prefusion conformation in combination with potent adjuvants, use of the RBD only as an immunogen instead of the whole S protein [67, 68] , other rationally designed immunogens [69] , other (non-Adeno) vector vaccines including replication-competent vectors [55, 70] , self-amplifying RNA vaccines [71] , live-attenuated vaccines [55] , DNA vaccines [72] , and intranasally applied vaccines with the potential to induce local immunity at the site of virus entry [73] . cache = ./cache/cord-337712-ylqgraos.txt txt = ./txt/cord-337712-ylqgraos.txt === reduce.pl bib === id = cord-335652-v98gv5uf author = Salazar, Cecilia title = Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date = 2020-05-10 pages = extension = .txt mime = text/plain words = 2063 sentences = 131 flesch = 48 summary = Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. This global health emergency has deployed international efforts to apply genomic epidemiology to track the spread of SARS-CoV-2 in real time. The recent development of targeted sequencing protocols by the ARTIC Network [3] , open sharing of genomic data through the GISAID (www.gisaid.org) database and straightforward bioinformatic tools for viral phylogenomics [4] , provides the opportunity to reconstruct global spatio-temporal dynamics of the COVID-19 pandemic with unprecedented comprehensiveness and resolution. We therefore aimed to characterize the spatio-temporal dynamics of SARS-CoV-2 by sequencing around 10% of cases occurred during the first week of outbreak in Montevideo, allowing us to identify transmission patterns, geographic origins and genetic variation among local strains. cache = ./cache/cord-335652-v98gv5uf.txt txt = ./txt/cord-335652-v98gv5uf.txt === reduce.pl bib === id = cord-335137-5qt286kc author = Chatterjee, Swapan K. title = Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19 date = 2020-08-11 pages = extension = .txt mime = text/plain words = 7124 sentences = 369 flesch = 47 summary = It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. The most significant surface protein is spike glycoprotein which interferes in establishing the association between the human respiratory epithelial cells to the virus via cell surface membrane receptor angiotensin-converting enzyme 2 (ACE2) and finally establishes the host tropism (Li et al., 2003) . A recent study suggests that prediction of SARS-CoV-2 spike glycoprotein structure, glycan shield pattern and pattern of glycosylation has great inference on understanding the viral camouflage as well as the outline of cell entry, and also facilitate the development of new small-molecule drugs, vaccines, antibodies, and screening of the human host targets (Song et al., 2018) . Various studies have proved that SARS-CoV-2 infection initiation and spread of disease into the host cells mainly depends upon S protein priming by TMPRSS2 (Transmembrane protease serine type 2), the serine protease. cache = ./cache/cord-335137-5qt286kc.txt txt = ./txt/cord-335137-5qt286kc.txt === reduce.pl bib === id = cord-337812-arivkkj0 author = Chu, Ling-Hon Matthew title = Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry date = 2006-03-07 pages = extension = .txt mime = text/plain words = 6860 sentences = 286 flesch = 52 summary = To screen the substrate specificity of SARS-CoV 3CL pro in a rapid and highthroughput manner in contrast to the traditional tedious procedures, we applied the matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOF MS) analysis in combination with the novel "cartridge replacement" solid-phase peptide synthesis approach to investigate the biological significance of amino acid residues in the P2, P3, P4, P1¢, P2¢, and P3¢ positions that are flanking the conserved Gln residue in the P1 position at the SARS-CoV 3CL pro cleavage site (Schechter and Berger 1967; Fan et al. In this study, we used MALDI-TOF MS analysis in combination with the solid-phase peptide synthesis approach to examine the biological significance of amino acid residues in a total of six target positions at the SARS-CoV 3CL pro cleavage sites, including the P2, P3, and P4 positions at the amino side of the P1 position; and the P1¢, P2¢, and P3¢ positions at the carboxyl side of the P1 position (Table 1) . cache = ./cache/cord-337812-arivkkj0.txt txt = ./txt/cord-337812-arivkkj0.txt === reduce.pl bib === id = cord-336775-d4hi9myk author = Kirtipal, Nikhil title = From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses date = 2020-08-13 pages = extension = .txt mime = text/plain words = 8606 sentences = 442 flesch = 46 summary = Abstract Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – diseases termed as COVID-19. Hence, acute respiratory distress syndrome (ARDS) is caused by cytokine storm that triggers a destruction in host cells via immune system and subsequently results into multiple organs failure or death as stated in case of SARS-CoV-2 outbreak; similar observations were noted in case of SARS-CoV infection (Kumar et al., 2020) . When developing novel therapeutic strategies to check the immunoregulatory cytokines such as TNFβ and IL6, investigation should be considered on the viral strain and targeted organ specificity; for example, SARS-CoV-2 has more affinity to ACE2 which are scattering on different organs like lung and kidney while MERS-like CoV can even infect T-cells. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) cache = ./cache/cord-336775-d4hi9myk.txt txt = ./txt/cord-336775-d4hi9myk.txt === reduce.pl bib === id = cord-338243-njkhwkwk author = Zhang, Dayi title = Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital date = 2020-06-23 pages = extension = .txt mime = text/plain words = 2831 sentences = 158 flesch = 51 summary = title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Cabin Hospital and found a striking high level of (0.5–18.7) × 103 copies/L after disinfection with sodium hypochlorite. In septic tanks, disinfection achieved free chlorine > 6.5 mg/L for 1.5 hours when the dosage of sodium hypochlorite was 800 g/m 3 , meeting well with the guideline for emergency treatment of medical sewage containing SARS-CoV-2 suggested by China CDC. Septic tanks can behave as a long-term source J o u r n a l P r e -p r o o f to release SARS-CoV-2 viral RNA into waters when disinfection is not sufficient and challenges public health via potentially spreading viruses in drainage pipelines. cache = ./cache/cord-338243-njkhwkwk.txt txt = ./txt/cord-338243-njkhwkwk.txt === reduce.pl bib === id = cord-337430-c2vdnml7 author = Timpka, Toomas title = Sports Health During the SARS-Cov-2 Pandemic date = 2020-05-02 pages = extension = .txt mime = text/plain words = 2261 sentences = 122 flesch = 47 summary = In December 2019, the Chinese city of Wuhan reported an outbreak of SARS-Cov-2 (severe acute respiratory syndrome coronavirus-2) infection that causes the Covid-19 disease, an atypical pneumonia [1] . The national public health agencies choose social distancing regulations based on an overall assessment of how critical certain activities are for society as a whole and whether motivation to comply with the rules can be assumed. During the SARS-Cov-2 pandemic, effectively all population-level interventions include the recommendation that social contacts with the elderly, and especially the senior elderly, are to be reduced to an absolute minimum. Sports organisations should develop a pandemic response strategy that addresses the needs of its athletes and coaches, while complying with the regulations and recommendations issued by the government and national public health agency. The temporary frameworks for organised sports practice and competitions must be developed based on the social distancing and quarantine protocols activated during the pandemic. cache = ./cache/cord-337430-c2vdnml7.txt txt = ./txt/cord-337430-c2vdnml7.txt === reduce.pl bib === id = cord-338775-gh3a0wuf author = Gulersen, Moti title = Histopathological evaluation of placentas after diagnosis of maternal SARS-CoV-2 infection date = 2020-08-15 pages = extension = .txt mime = text/plain words = 2512 sentences = 152 flesch = 44 summary = Study Design Retrospective cohort study of women diagnosed with SARS-CoV-2 infection who delivered at a single center from April 9th to April 27th, 2020, and had placental specimens reviewed by pathology. Histopathological characteristics were evaluated in each placenta and the incidence of these findings were compared between placentas after diagnosis of maternal SARS-CoV-2 infection and historical controls, as well as between placentas from patients with or without typical symptoms related to infection. Conclusions Based on our data, there are no significant placental histopathological changes that occur after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared to a gestational age-matched historical control group. The results of our study did not demonstrate significant placental histopathological changes 229 occurring after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared 230 to a gestational-age-matched historical control group with a similar incidence of antepartum or Pathology for examination or due to history of melanoma. cache = ./cache/cord-338775-gh3a0wuf.txt txt = ./txt/cord-338775-gh3a0wuf.txt === reduce.pl bib === id = cord-339009-wcoch07b author = File, Thomas M. title = Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy date = 2012-08-23 pages = extension = .txt mime = text/plain words = 6023 sentences = 324 flesch = 50 summary = Because the causative agent of SARS is • one or more clinical findings of respiratory illness (e.g. cough, contagious, preventative measures focus on avoidance of exposhortness of breath, difficulty in breathing, or hypoxia) sure, and infection control strategies for suspected patients and • travel within 10 days of onset of symptoms to an area with contacts. [12] Of the reported cases was updated to include laboratory criteria for evidence of infection 64% were from China, 19% from Hong Kong, 8% from Taiwan, with the SARS-associated coronavirus (SARS-CoV). Algorithm for evaluating and managing patients requiring hospitalization for radiographically confirmed pneumonia, in the absence of person-toperson transmission of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) anywhere in the world. cache = ./cache/cord-339009-wcoch07b.txt txt = ./txt/cord-339009-wcoch07b.txt === reduce.pl bib === id = cord-338544-eph89g47 author = Spuntarelli, Valerio title = COVID-19: is it just a lung disease? A case-based review date = 2020-07-28 pages = extension = .txt mime = text/plain words = 2279 sentences = 142 flesch = 44 summary = COVID-19 pandemic reached 3.78 million confirmed reported cases worldwide, and it is generally associated to the acronym that precedes its name: severe acute respiratory syndrome (SARS). A prospective study investigating left ventricular performance in 46 patients with severe acute respiratory syndrome showed subclinical diastolic impairment without systolic involvement [3] . Pathological findings of COVID-19 associated with acute respiratory distress syndrome showed few interstitial mononuclear inflammatory infiltrates, but no other substantial damage in the heart tissue [7] . A case report highlights myocarditis as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia in an otherwise healthy 53-year-old white woman [8] . The authors concluded that the presence of the characteristic features of symmetric, multifocal lesions with thalamic involvement suggests that this is a case of acute necrotizing hemorrhagic encephalopathy associated with COVID-19. Guillain Barre syndrome associated with COVID-19 infection: a case report cache = ./cache/cord-338544-eph89g47.txt txt = ./txt/cord-338544-eph89g47.txt === reduce.pl bib === id = cord-338205-sy91rnse author = Li, Chenxi title = Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) date = 2020-07-02 pages = extension = .txt mime = text/plain words = 7515 sentences = 436 flesch = 51 summary = With limited understanding of COVID-19, it is difficult to exclude SARS-CoV-2 infection based on a single negative PCR result, especially when testing was used for upper respiratory tract specimens. The study found that SARS-CoV-2 could be detected in all primer-probe sets applied in the qRT-PCR tests, but significant discrepancy was observed in the detection limit and the ability to identify negatives and positives with a lower viral load. Compared with the qRT-PCR kit, nested RT-PCR analysis showed higher sensitivity and specificity, indicating that it is more suitable for clinical application to detect SARS-CoV-2 in cases with low viral load. In cases where RT-PCR assays are negative and there is a strong epidemiological link to SARS-CoV-2 infection, paired serum samples (in the acute and convalescent-phase) could support diagnosis once validated serology tests are available with the initial samples collected in the first week of COVID-19 and the second collected after 2-4 weeks [28] . cache = ./cache/cord-338205-sy91rnse.txt txt = ./txt/cord-338205-sy91rnse.txt === reduce.pl bib === id = cord-338468-c0jv3i1t author = Kanduc, Darja title = From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date = 2020-07-16 pages = extension = .txt mime = text/plain words = 4143 sentences = 234 flesch = 41 summary = Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. In the wake of such results, in order to validate (or, as well, invalidate) the cross-reactivity hypothesis, investigation was expanded here by analyzing the peptide sharing between the human host and immunoreactive epitopes that are also present in SARS-CoV-2. Table 2 documents that numerous immunoreactive SARS-CoV-2 epitopes are composed mostly or, in many instances, uniquely of peptide sequences shared with human proteins. This study shows that hexapeptides from immunoreactive epitopes present in SARS-CoV-2 are widespread among a high number of human proteins. Table S2 : Hexapeptide sharing between 233 epitopes present in SARS-CoV-2 and human proteins. Table S3 : List and short description of 460 human proteins that share hexapeptides with the 233 SARS-CoV-2 epitopes. cache = ./cache/cord-338468-c0jv3i1t.txt txt = ./txt/cord-338468-c0jv3i1t.txt === reduce.pl bib === id = cord-338923-hc7gagnq author = Jääskeläinen, AJ title = Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation date = 2020-06-15 pages = extension = .txt mime = text/plain words = 2101 sentences = 131 flesch = 53 summary = We compared the performance of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-CoV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). In this study, we assessed the specificity and sensitivity of six commercial immunoassays for the detection of SARS-CoV-2 antibodies, including two rapid lateral flow tests, in comparison with a neutralisation test. cache = ./cache/cord-338923-hc7gagnq.txt txt = ./txt/cord-338923-hc7gagnq.txt === reduce.pl bib === id = cord-340516-9dfaqsv7 author = Moore, Anne C. title = Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date = 2020-09-06 pages = extension = .txt mime = text/plain words = 6679 sentences = 335 flesch = 48 summary = We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody. cache = ./cache/cord-340516-9dfaqsv7.txt txt = ./txt/cord-340516-9dfaqsv7.txt === reduce.pl bib === id = cord-339762-lh8czr0a author = Ng, Dianna L. title = Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 date = 2016-03-31 pages = extension = .txt mime = text/plain words = 3207 sentences = 162 flesch = 38 summary = title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a sputum specimen of a patient who died of respiratory and renal failure in Saudi Arabia in 2012. Although the pathogenesis of severe and fatal MERS-CoV infection is unknown, these postmortem findings provide critical insights, including evidence that pneumocytes are important targets, suggesting that direct cytopathic effects contribute to MERS-CoV respiratory symptoms. cache = ./cache/cord-339762-lh8czr0a.txt txt = ./txt/cord-339762-lh8czr0a.txt === reduce.pl bib === id = cord-338973-73a7uvyz author = Xu, Jiabao title = Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date = 2020-02-22 pages = extension = .txt mime = text/plain words = 7110 sentences = 426 flesch = 57 summary = After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections. cache = ./cache/cord-338973-73a7uvyz.txt txt = ./txt/cord-338973-73a7uvyz.txt === reduce.pl bib === id = cord-339859-anatn295 author = Paret, Michal title = SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress date = 2020-04-17 pages = extension = .txt mime = text/plain words = 1286 sentences = 105 flesch = 59 summary = title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress We report two cases of SARS-CoV-2 infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time RT-PCR-based testing for SARS-CoV-2 for febrile infants in an outbreak setting. [2] [3] [4] Even in the setting of asymptomatic or mildly symptomatic infection, children may represent a source of SARS-CoV-2 spread in community or hospital settings, so understanding the spectrum of COVID-19 illness in infants, particularly regarding conditions that result in hospitalization, is crucial to establishment of effective infection control interventions. Vital signs and pertinent laboratory findings appear in the A real-time RT-PCR assay performed at the New York State Department of Health detected SARS-CoV-2 RNA in the patient's NP sample. cache = ./cache/cord-339859-anatn295.txt txt = ./txt/cord-339859-anatn295.txt === reduce.pl bib === id = cord-340305-jtvn9tlm author = Cimolai, Nevio title = A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19 date = 2020-09-19 pages = extension = .txt mime = text/plain words = 5105 sentences = 294 flesch = 40 summary = At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Others have found strong correlations between neutralizing antibodies and EIA-detected antibodies to various SARS-CoV-2 antigens [41, 42] .Some have found diversity in immune responses contingent on the nature of presenting disease [38, 43] . With the availability of viral antigen, most scientists in the know-how would be able to fashion a test for antibody determination in short order and most would likely choose an enzyme immunoassay (EIA) (or nearly equivalent non-enzymebased assay) for its potential of automation and widespread use. Sensitive and specific detection of low-level antibody responses in mild Middle East Respiratory Syndrome coronavirus infections A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients cache = ./cache/cord-340305-jtvn9tlm.txt txt = ./txt/cord-340305-jtvn9tlm.txt === reduce.pl bib === id = cord-339665-nwwutduy author = Patel, Ami title = Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date = 2020-07-29 pages = extension = .txt mime = text/plain words = 5258 sentences = 286 flesch = 52 summary = Prior work with the related coronaviruses, SARS-CoV and MERS-CoV, delineated that the Spike protein of these viruses was an important target for development of neutralizing antibodies, and in animal viral challenges vaccine targeted immunity (reviewed in (Du et al., 2009; Roper and Rehm, 2009; Thanh Le et al., 2020) (Liu et al., 2018; Muthumani et al., 2015; van Doremalen et al., 2020a) . These memory titers were comparable to those observed in other reported protection studies in macaques performed at the acute phase of the vaccine-induced immune response (Gao et al., 2020; van Doremalen et al., 2020b; Yu et al., 2020) and those reported in the sera of convalescent patients (Ni et al., 2020; Robbiani et al., 2020) . Our study and other published reports show that DNA vaccination with candidates targeting the full-length SARS-CoV-2 spike protein likely increase the availability of T cell immunodominant epitopes leading to a broader and more potent immune response, compared to partial domains and truncated immunogens. cache = ./cache/cord-339665-nwwutduy.txt txt = ./txt/cord-339665-nwwutduy.txt === reduce.pl bib === id = cord-338436-0z828org author = Tzou, Philip L. title = Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date = 2020-09-09 pages = extension = .txt mime = text/plain words = 8193 sentences = 522 flesch = 46 summary = Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. cache = ./cache/cord-338436-0z828org.txt txt = ./txt/cord-338436-0z828org.txt === reduce.pl bib === id = cord-342220-lrqt2gcw author = Dearlove, Bethany title = A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants date = 2020-09-22 pages = extension = .txt mime = text/plain words = 7874 sentences = 415 flesch = 49 summary = Although the closest currently available bat sequences are fairly divergent from SARS-CoV-2, their characteristics (insertion at S1/S2 cleavage site, high diversity, and similarity between specific gene fragments and particular strains) together with their known adaptive properties (high recombination and host-switching rates and evidence of positive selection) support that these bat viruses constitute While the evolutionary rate is likely to decrease over time (18) , it is important to monitor the introduction of any mutation that may compromise the potential efficacy of vaccine candidates derived from the first available SARS-CoV-2 sequences. In S, only site 614 was estimated to be under diversifying selection in a majority of subsampled alignments (58%); evidence of diversifying selection indicates that genetic diversity increases in the viral population (i.e., there was a higher proportion of mutations causing an amino acid change than not at site 614, or, the nonsynonymous/synonymous substitution rates ratio, dN/dS, was over 1, P < 0.1) (SI Appendix, Fig. S4 ). cache = ./cache/cord-342220-lrqt2gcw.txt txt = ./txt/cord-342220-lrqt2gcw.txt === reduce.pl bib === id = cord-342383-ckswlo9o author = Pawlowski, C. title = Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations date = 2020-07-28 pages = extension = .txt mime = text/plain words = 5479 sentences = 273 flesch = 51 summary = Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI: (0.32, 0.64), p-value: 6.9e-05). Given this study population, we assess the rates of SARS-CoV-2 infection among individuals who did and did not receive one of 18 vaccines in the past 1, 2, and 5 years relative to the date of PCR testing. In Figure 6 , we present the results from the tipping point analysis on the statistically significant associations between vaccination and reduced rates of SARS-CoV-2 infection in the overall study population. For example, for the polio vaccine at the 1 year time horizon, an unobserved confounder with a relative risk of 2.78 which is prevalent in 17.8% of the vaccinated cohort and 0% of the unvaccinated cohort could explain the differences in SARS-CoV-2 infection rates that we observe in the data. cache = ./cache/cord-342383-ckswlo9o.txt txt = ./txt/cord-342383-ckswlo9o.txt === reduce.pl bib === id = cord-341254-xnj6slby author = Li, Hua title = A new and rapid approach for detecting COVID‐19 based on S1 protein fragments date = 2020-06-05 pages = extension = .txt mime = text/plain words = 1945 sentences = 120 flesch = 46 summary = Based on it, the detection of IgM/IgG in blood became an optional approach to improve the diagnosis, especially for the COVID-19 patient with negative nucleic acid test result. 2. Colloidal gold-labeled mouse-antihuman lgM/lgG antibody was manufactured by SAIYA Hebei Biotechnology Co., Ltd. To obtain the well-performance antibody, the antibody was selected for functional test including the positive and negative coincidence rates, minimum test threshold, and accelerated stability. Due to only around 50% positive rate of SARS-CoV-2 nucleic acid test 8, 12 under various condition of sample collection and storage, viral infection regions, RNA extraction methods, the quality of nucleic acid detection kit, and so on, 13 detection of IgM/IgG became a powerful approach for the early diagnosis of COVID-19 and could help identify the patients with negative nucleic acid but with obvious clinical symptoms. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis cache = ./cache/cord-341254-xnj6slby.txt txt = ./txt/cord-341254-xnj6slby.txt === reduce.pl bib === id = cord-341234-2zgfcrwc author = Hallak, Jorge title = Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil date = 2020-09-02 pages = extension = .txt mime = text/plain words = 3614 sentences = 178 flesch = 41 summary = title: Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil Recently, a group of 27 experts from 15 countries and five continents has argued that postponing andrological services and male infertility care during the COVID-19 pandemic could permanently compromise the prospects of biological parenthood for 'time-sensitive' patients, thus resulting in a devastating psychological impact on men undergoing fertility-related treatment (1) . A recent probabilistic pilot study conducted in seven districts of the city of São Paulo to estimate the prevalence of herd immunity showed that about 5.2% individuals had SARS-CoV-2 IgG antibodies, corresponding to an overall infection rate We reiterate that andrological services and male infertility care cannot be considered low priority during the current SARS-CoV-2 pandemic, particularly for the most vulnerable patients, like those with cancer, patients using immunosuppressive therapy, and the azoospermic/cryptozoospermic men under medical or post-surgical treatment to improve spermatogenesis. cache = ./cache/cord-341234-2zgfcrwc.txt txt = ./txt/cord-341234-2zgfcrwc.txt === reduce.pl bib === id = cord-339344-qd73h1ie author = Simon, David title = Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion date = 2020-07-24 pages = extension = .txt mime = text/plain words = 4094 sentences = 202 flesch = 43 summary = To test whether differences in social exposure between the groups account for the low prevalence of SARS-CoV-2 IgG responses in IMID patients treated with cytokine inhibitors, we assessed exposure risk variables (contact with persons with a respiratory infection, presence at workplace outside home, travel to risk areas) of IMID patient groups and control groups. The low seroprevalence of SARS-CoV-2 in anti-cytokine treated IMIDs could have two principle explanations: While (i) the four groups were recruited in the same region, (ii) the HC control group having the highest prevalence for SARS-CoV-2 IgG was in direct contact with the IMID patients and (iii) all participants were exposed to similar detailed information regarding social behavior during the outbreak of the COVID-19 pandemic in Germany, IMID patients may have followed an even more stringent exposure prophylaxis than healthy individuals. cache = ./cache/cord-339344-qd73h1ie.txt txt = ./txt/cord-339344-qd73h1ie.txt === reduce.pl bib === id = cord-343317-97n1j0jj author = Duan, Xiaohua title = Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date = 2020-05-02 pages = extension = .txt mime = text/plain words = 3776 sentences = 222 flesch = 56 summary = Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. The organoids infected with SARS-CoV-2 pseudo-entry virus at MOI=0.01 showed a strong signal at 24 hpi (Fig. 2a) . The mRNAs of SARS-CoV-2 pseudo-entry virus, including VSV-NS, VSV-N, and VSV-M, were detected in all five cell populations (Fig. 2f) , but not in the uninfected COs (Extended Data Fig. 2f) . Immunohistochemistry detected luciferase in ACE2 + and Villin + cells, suggesting these are permissive to SARS-CoV-2 pseudo-entry virus infection in vivo (Fig. 2k) . Next, we adapted hPSC-COs to a high throughput screening platform and probed the Prestwick FDA-approved drug library to identify drug candidates capable of blocking SARS-CoV-2 pseudo-virus infection. cache = ./cache/cord-343317-97n1j0jj.txt txt = ./txt/cord-343317-97n1j0jj.txt === reduce.pl bib === id = cord-340049-6rqmc89u author = Salvatori, Giovanni title = SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines date = 2020-06-03 pages = extension = .txt mime = text/plain words = 1411 sentences = 86 flesch = 44 summary = Evidence of the key role played by the S protein in counteracting coronavirus infection came from studies on human-neutralizing antibodies from rare memory B cells of individuals infected with SARS-CoV [2] or MERS-CoV [3] . Journal of Translational Medicine antibody responses, and vigorously neutralized SARS-CoV-2 S-mediated entry into cells, thus further encouraging the use of this molecular target for vaccination and immunotherapies [4] . Given the above and that the coronavirus S glycoprotein is surface-exposed and mediates entry into host cells by interacting with angiotensin-converting enzyme 2 (ACE2), it rapidly became the main target of neutralizing antibodies and the focus of therapeutic and vaccine design. Several companies and research institutes have started developing a vaccine that has the SARS-CoV-2 protein S as its target (see Table 1 ), although the various vaccination strategies show a differing ability to induce in the host both an antibody-mediated humoral response and a cell response mediated by CD4 or CD8 T lymphocytes in preclinical models. cache = ./cache/cord-340049-6rqmc89u.txt txt = ./txt/cord-340049-6rqmc89u.txt === reduce.pl bib === id = cord-343827-jo61t3m0 author = Qian, Qun title = Direct evidence of active SARS-CoV-2 replication in the intestine date = 2020-07-08 pages = extension = .txt mime = text/plain words = 1314 sentences = 98 flesch = 53 summary = We investigated the presence of virions and pathological changes in surgical rectal tissues of a clinically confirmed COVID-19 patient with rectal adenocarcinoma. RNA of SARS-CoV-2 was detected in surgically resected rectal specimens, but not in samples collected on 37 day after discharge. Notably, coincidence with rectal tissues of surgical specimens tested nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Notably, fecal samples remained positive for SARS-CoV-2 RNA nearly 5 weeks after the viral clearance from the upper respiratory tract in COVID-19 patients [8] . To clarify the above questions, we performed a retrospective study to detect the presence of SARS-CoV-2 virions and determine the pathological changes in rectal tissues of this patient. Samples of rectal tissues, succus entericus and intestinal mucosa of ileostomy, and rectal mucosa were tested for SARS-CoV-2 nucleic acid using qRT-PCR. cache = ./cache/cord-343827-jo61t3m0.txt txt = ./txt/cord-343827-jo61t3m0.txt === reduce.pl bib === id = cord-340042-intxyu46 author = Chaudhry, Sundas Nasir title = New insight on possible vaccine development against SARS-CoV-2 date = 2020-09-11 pages = extension = .txt mime = text/plain words = 5457 sentences = 260 flesch = 43 summary = In December 2019, a novel virus, namely COVID-19, caused by SARS-CoV-2, developed from Wuhan, Hubei territory of China, which used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Different subunits of spike proteins like the S1 and S2 subunits, and the receptor-binding domain (RBD) are the critical elements for the formation of a vaccine against the newly emerged virus that helped in producing T cell responses and protective immunity against SARS-CoV-2 [29] . The recombinant protein is known as one of the emerging fields for the development of a vaccine against viruses due to several properties including tight binding to specific ACE-2 receptor, provoke immune protection against viral infections, increase antibody-dependent viral entry, and promote antigenicity against virus like SARS-CoV [52] . cache = ./cache/cord-340042-intxyu46.txt txt = ./txt/cord-340042-intxyu46.txt === reduce.pl bib === id = cord-337825-ujq9mxk7 author = Chen, Bin title = Overview of lethal human coronaviruses date = 2020-06-10 pages = extension = .txt mime = text/plain words = 13423 sentences = 761 flesch = 51 summary = Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine cache = ./cache/cord-337825-ujq9mxk7.txt txt = ./txt/cord-337825-ujq9mxk7.txt === reduce.pl bib === id = cord-341287-i1hyk962 author = Smith, Trevor R. F. title = Immunogenicity of a DNA vaccine candidate for COVID-19 date = 2020-05-20 pages = extension = .txt mime = text/plain words = 7803 sentences = 446 flesch = 54 summary = Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. In subjects immunized with INO-4700 (MERS-CoV S protein DNA vaccine) durable neutralizing antibodies (nAbs) and T cell immune responses were measured, and a seroconversion rate of 96% was observed and immunity was followed for 60 weeks in most study volunteers 9 . We followed the induction of immunity by the selected immunogen in mice and guinea pigs, measuring SARS-CoV-2 S protein-specific antibody levels in serum and in the lung fluid, and antibody functionality through competitive inhibition of ACE2 binding, pseudovirus and live virus neutralization. In summary, humoral immunogenicity testing in both mice and guinea pigs revealed the COVID-19 vaccine candidate, INO-4800, was capable of eliciting functional blocking antibody responses to SARS-CoV-2 spike protein. cache = ./cache/cord-341287-i1hyk962.txt txt = ./txt/cord-341287-i1hyk962.txt === reduce.pl bib === id = cord-342569-ja96xfns author = Azer, Samy A. title = COVID-19: Pathophysiology, diagnosis, complications and Investigational therapeutics date = 2020-08-05 pages = extension = .txt mime = text/plain words = 2669 sentences = 186 flesch = 46 summary = On 31 December 2019, the Chinese authorities reported to the World Health Organisation (WHO) an emerging of a novice coronavirus, currently the virus is known as SARS-CoV-2 and the disease name is coronavirus-19 disease (COVID19) , that has emerged in patients from Wuhan city, Hubel Province [1] . Recently it was debated that targeting the Notch signalling to prevent SARS-CoV-2 infection and interfering with the progression of COVID-19associated heart and lungs disease pathogenesis [13] . It is not clear whether the observed SARS-CoV-2-associated liver injury is cause by direct viral injury or related to hepatoxic drugs, coexisting systemic inflammatory changes, sepsis, respiratory distress syndrome-induced hypoxia, and multiple organ failure [18] . In patients with type 2 diabetes mellitus who are infected with COVID-19, it is important to remember that two receptor proteins ACE-2 and dipeptidyl peptidase-4 (DPP-4) are test can detect IgM, and IgG antibodies against SARS-CoV-2 in the serum, plasma, and whole blood [23] . cache = ./cache/cord-342569-ja96xfns.txt txt = ./txt/cord-342569-ja96xfns.txt === reduce.pl bib === id = cord-344266-ug2uew71 author = Crema, E. title = The SARS-COV-2 outbreak around the Amazon rainforest: the relevance of the airborne transmission date = 2020-08-07 pages = extension = .txt mime = text/plain words = 3951 sentences = 215 flesch = 54 summary = Currently, this phenomenon has gained tragic relevance due to the uncontrolled dispersion of the Covid-19 throughout the planet, since airborne transmission is one of the forms of viral contamination, as well as the direct reception of drops exhaled by a contaminated person and the contact with infected surfaces. A relevant study issued in the journal Nature revealed the existence of the RNA of the SARS-COV-2 in aerosols collected from the air of several closed environments and open places of two hospitals in Wuhan dedicated only to patients infected with Covid-19 (12) . This indication is based only on old studies about the direct transmission by larger drops, dangerously ignoring the contamination by the virus airborne in droplets that remain suspended in the air for several hours, and even days after the environment has been visited by an infected person. cache = ./cache/cord-344266-ug2uew71.txt txt = ./txt/cord-344266-ug2uew71.txt === reduce.pl bib === id = cord-342902-y1v8wzxq author = Yuan, Shuofeng title = Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters date = 2020-10-07 pages = extension = .txt mime = text/plain words = 5692 sentences = 291 flesch = 45 summary = Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. We found that co-application of clofazimine and remdesivir impacts SARS-CoV-2 replication in a manner that extends beyond the additive combinatorial activity predicted by the Bliss independence model (maximal Bliss Synergy Score of 44.28; Figure 5a , Extended Data Figure 2) , and indicates these two drugs harbor a synergistic antiviral relationship. cache = ./cache/cord-342902-y1v8wzxq.txt txt = ./txt/cord-342902-y1v8wzxq.txt === reduce.pl bib === id = cord-342796-f7n8sxbu author = Stowe, J. title = Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3923 sentences = 218 flesch = 48 summary = Findings: The risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Severity and risk of death among individuals with a coinfection: The mortality rate among individuals with a SARS-CoV-2 and influenza coinfection and those with SARS-CoV-2 infection who tested negative for influenza was calculated by dividing the number of deaths by the total number of individuals tested by age group. We also found strong evidence that coinfection with influenza and SARS-CoV-2 was associated with an increased risk of death or severe disease and that this appears to be beyond the additive effect of the two viruses acting independently. cache = ./cache/cord-342796-f7n8sxbu.txt txt = ./txt/cord-342796-f7n8sxbu.txt === reduce.pl bib === id = cord-346819-11fkgzaa author = Khan, Mohd Imran title = Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date = 2020-09-03 pages = extension = .txt mime = text/plain words = 4405 sentences = 291 flesch = 57 summary = title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . cache = ./cache/cord-346819-11fkgzaa.txt txt = ./txt/cord-346819-11fkgzaa.txt === reduce.pl bib === id = cord-343196-vlwzzrgc author = Kiambi, Stella title = Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017 date = 2018-11-28 pages = extension = .txt mime = text/plain words = 1494 sentences = 71 flesch = 50 summary = The MERS-CoV RNA-positive animals belonged to two different dromedary camel herds in Dabel and Lombolio, which are both located within Isiolo country. To experimentally confirm the presence of two independently circulating MERS-CoV strains and to rule out sample cross-contamination, we generated complete MERS-CoV genome sequences using a previously established protocol 10 . Other confirmed MERS-CoVpositive samples were assigned to two different MERS-CoV isolates ("Dabel" or "Lombolio") by amplifying and sequencing single-nucleotide polymorphisms in the spike gene and the open reading frame 3 (Supplementary Table) . The previously described clade C African MERS-CoV strains 4,5 had several mutations in the spike protein, which is responsible for cellular receptor interaction, virus entry, and antibody-directed virus neutralization 12 . An explanation for this observation may again be a lack of testing of imported animals and/or the fact that previous clade A/B MERS-CoV infections may have established herd immunity in the Arabian dromedary populations. cache = ./cache/cord-343196-vlwzzrgc.txt txt = ./txt/cord-343196-vlwzzrgc.txt === reduce.pl bib === id = cord-342538-5bwsm290 author = Izquierdo Lara, R. W. title = Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing date = 2020-09-22 pages = extension = .txt mime = text/plain words = 5031 sentences = 281 flesch = 56 summary = Here we have explored the possibility of using next-generation sequencing (NGS) of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level from routine wastewater testing, and compared these results with the virus diversity in patients from the Netherlands and Belgium. Low frequency variant (LFV) analysis showed that some known LFVs can be associated with particular clusters within a clade, different to those of their consensus sequences, suggesting the presence of at least 2 clades within a single sewage sample. Moreover, we detected a total of 51 novel mutations present in sewage consensus sequences that were not previously reported (supplementary Table S2 ), of which 48 were supported by coverage above the set thresholds to be considered as high quality (coverage >30x for Nanopore; and coverage >5X and Phred score >30 for Illumina). cache = ./cache/cord-342538-5bwsm290.txt txt = ./txt/cord-342538-5bwsm290.txt === reduce.pl bib === id = cord-343528-5283jsnu author = Zhang, Zhao title = Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date = 2016-05-04 pages = extension = .txt mime = text/plain words = 4745 sentences = 251 flesch = 55 summary = Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV's evolutionary history and the positive selection sites in MERS-CoV's S protein might enable it to infect human. In order to study the temporal and spatial pattern of MERS-CoV transmission, a maximum clade credibility (MCC) tree was constructed using MERS-CoV whole genome sequences without recombinant strains (Fig. 3c) . The amino acid sites under positive selection in MERS-CoV S protein, especially those in its receptor binding domain, might have facilitated its cross-species transmission from animal host to human. All authors reviewed the manuscript. cache = ./cache/cord-343528-5283jsnu.txt txt = ./txt/cord-343528-5283jsnu.txt === reduce.pl bib === id = cord-342756-rgm9ffpk author = Senger, Mario Roberto title = COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date = 2020-10-02 pages = extension = .txt mime = text/plain words = 16108 sentences = 1024 flesch = 51 summary = Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment. cache = ./cache/cord-342756-rgm9ffpk.txt txt = ./txt/cord-342756-rgm9ffpk.txt === reduce.pl bib === id = cord-343302-g9vcchrh author = Agrawal, Anurodh Shankar title = Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date = 2016-08-19 pages = extension = .txt mime = text/plain words = 4795 sentences = 212 flesch = 49 summary = title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Here, we further characterized this novel human mAb in our Tg mouse model of MERS-CoV infection and showed prophylactic and therapeutic protection of mice treated with m336 before and after a lethal challenge with the virus, respectively. In our studies, we noted that passively transferred with 1 mg and 0.1 mg of m336 monoclonal antibodies to individual mice 12 h prior to challenge with 1,000 LD 50 of MERS-CoV resulted in 100% and 75% protection against lethality, respectively (Fig. 1) , suggesting that using 0.1 mg m336/mouse as a prophylaxis is suboptimal to completely neutralize viral infection, thereby allowing residual viruses to replicate within lungs during the course of infection. cache = ./cache/cord-343302-g9vcchrh.txt txt = ./txt/cord-343302-g9vcchrh.txt === reduce.pl bib === id = cord-348192-ibohbjfb author = Odih, Erkison E. title = Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? date = 2020-06-09 pages = extension = .txt mime = text/plain words = 2676 sentences = 163 flesch = 49 summary = Endemic and epidemic transmission of multiple feco-oral pathogens via this route continues to be documented in areas without safely managed sanitation, and, therefore, the risk of SARS-CoV-2 transmission needs to be evaluated, tracked, and forestalled in such settings. Furthermore, environmental surveillance of SARS-CoV-2 in wastewater and accumulated human waste, as well as efforts to mitigate the virus' entry into unprotected household water sources, should be a priority part of the COVID-19 response in settings without safely managed sanitation for the duration of the pandemic. 3, 5, 6 Considerable concern has been expressed in the literature that the feco-oral transmission potential for SARS-CoV-2 places endoscopists, caregivers of diapered children who shed the virus, 7 and fecal transplant recipients 8 at high risk of contracting the infection. 20, 21 Although there are as yet no reports of transmission of SARS-CoV-2 via sewage or fecal matter in settings without safely managed sanitation, or recovery from household water, these examples demonstrate that feco-oral transmission by endemic pathogenic organisms is commonplace in these settings. cache = ./cache/cord-348192-ibohbjfb.txt txt = ./txt/cord-348192-ibohbjfb.txt === reduce.pl bib === id = cord-343517-vf32wxkx author = Lokman, Syed Mohammad title = Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date = 2020-04-11 pages = extension = .txt mime = text/plain words = 2745 sentences = 163 flesch = 53 summary = However, SARS-CoV-2 has emerged with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. The evolutionary distances showed that all the SARS-CoV-2 spike proteins cluster in the same node of the phylogenetic tree confirming the sequences are similar to Refseq YP_009724390 (Fig. 2) . cache = ./cache/cord-343517-vf32wxkx.txt txt = ./txt/cord-343517-vf32wxkx.txt === reduce.pl bib === id = cord-346960-3empldlo author = Plebani, M. title = Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity date = 2020-08-04 pages = extension = .txt mime = text/plain words = 2282 sentences = 134 flesch = 46 summary = In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. 54 SARS-CoV-2 negative subjects (33 healthcare workers, 21 autoimmune patients, 8 pregnant women) were included in the study ( Moreover, Liaison SARS-CoV-2 S1/S2 IgG (Diasorin, Sallugia-VC, Italy), ENZY-Well SARS-CoV-2 IgA and IgM were evaluated for the correlation with the neutralization results. . To provide insight on neutralization activity compared with immunoassays results, PRNT assay was performed on 52 samples from SARS-CoV-2 positive subjects. cache = ./cache/cord-346960-3empldlo.txt txt = ./txt/cord-346960-3empldlo.txt === reduce.pl bib === id = cord-345371-pjbviagq author = Lisi, Lucia title = Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2 date = 2020-07-23 pages = extension = .txt mime = text/plain words = 10648 sentences = 512 flesch = 37 summary = The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. Here, we review the recently published literature on the pharmacological treatments used so far and/or undergoing evaluation in clinical trials, with focus on the biochemical mechanisms of action of repurposed or investigational drugs, classified as agents directly targeting the virus ( Figure 1 and Table 1 ) and those used to treat the respiratory distress and inflammation associated with the cytokine release syndrome ( Figure 2 and Table 2 ). cache = ./cache/cord-345371-pjbviagq.txt txt = ./txt/cord-345371-pjbviagq.txt === reduce.pl bib === id = cord-341453-9yrvjlpx author = Clay, Candice C title = Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses date = 2014-03-19 pages = extension = .txt mime = text/plain words = 8130 sentences = 395 flesch = 48 summary = The aim of this study was to determine how the peripheral and mucosal immune responses to SARS-CoV infection compare in the aged and juvenile nonhuman primate host and to determine how this may impact viral replication levels. No virus was detected in any sample collected from either age group at 10 d.p.i. To determine if advanced age correlated with increased severity of lung pathology, a comprehensive histological analysis of the respiratory tract following SARS-CoV infection was conducted in aged and juvenile animals. To determine how mucosal cytokines in SARS-CoV infection compared to systemic responses and how age may impact mucosal cytokine expression; the inflammatory protein profile was evaluated by bead-based arrays in standardized-collected lung tissue from the proximal portion of the right caudal lobe. Although no age-dependent differences were observed in the frequency of naïve (CD45RA + CCR7+) CD8 T cells in peripheral blood, there were significantly lower levels of these cells in the lung and lymph node of aged animals during SARS-CoV infection ( Figure 6A -C; unpaired student T-tests). cache = ./cache/cord-341453-9yrvjlpx.txt txt = ./txt/cord-341453-9yrvjlpx.txt === reduce.pl bib === id = cord-346987-fbqqf00i author = Guo, Yongwen title = Controls of SARS-CoV-2 transmission in orthodontic practice date = 2020-06-05 pages = extension = .txt mime = text/plain words = 4660 sentences = 244 flesch = 47 summary = ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. What's more, the close contact between dental staffs and patients as well as the droplets and aerosols generated during treatment containing saliva and blood further increase the risk of SARS-CoV-2 transmission in dental practice 5 . We must constantly bear in mind that the threat of infection is not visible which poses a challenge on the orthodontic practice thus effective control measures should be taken to prevent the transmission of SARS-CoV-2 and protect both practitioners and patients from the COVID-19. cache = ./cache/cord-346987-fbqqf00i.txt txt = ./txt/cord-346987-fbqqf00i.txt === reduce.pl bib === id = cord-348696-86nbwon2 author = Güemes-Villahoz, Noemi title = Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review date = 2020-08-18 pages = extension = .txt mime = text/plain words = 4199 sentences = 216 flesch = 43 summary = title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review A multicenter study which documented potential risk factors for SARS-CoV-2 transmission in patients requiring intubation [7] reported that unprotected eye contact with secretions from infected patients was the most predictive variable for transmission to healthcare workers. A recent study evaluated the ocular tropism of SARS-CoV-2 in patients with confirmed COVID-19. Of the 56 subjects investigated there was only one patient who gave a history of prior pterygium surgery, with conjunctivitis and a positive PCR result from the conjunctival swab highlighting the importance of an intact ocular surface in resisting virus invasion [25] . Despite ocular complications not being a common clinically detectable manifestation of SARS-CoV-2 infection, recent evidence suggests that ocular exposure may represent a major transmission route for the virus. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection SARS-CoV-2 RNA detection in tears and conjunctival secretions of COVID-19 patients with conjunctivitis cache = ./cache/cord-348696-86nbwon2.txt txt = ./txt/cord-348696-86nbwon2.txt === reduce.pl bib === id = cord-347706-r0rs3ls1 author = Roberts, Anjeanette title = Animal Models for Sars date = 2006 pages = extension = .txt mime = text/plain words = 3013 sentences = 139 flesch = 43 summary = Mice that recover from infection develop a neutralizing antibody response and are protected from subsequent challenge; antibody alone is sufficient to protect mice from replication of SARS-CoV in the lower respiratory tract and NK, NK-T, T, and B cells are not required for viral clearance. 13, 13b CoV disease, with weight loss and pneumonitis that begins with acute bronchiolitis and In summary, SARS-CoV replicates efficiently in the respiratory tract of young viremia occurs 1 to 2 days following infection and virus is detected in the liver and spleen in hamsters. As seen with the other animal models, the course of infection in experimentally infected nonhuman primates is short, with a rapid peak in viral replication and clearance of virus from the lungs by days 4 to 7 in different species. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice cache = ./cache/cord-347706-r0rs3ls1.txt txt = ./txt/cord-347706-r0rs3ls1.txt === reduce.pl bib === id = cord-345381-9cckppk2 author = Klimek, Ludger title = Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) date = 2020-09-07 pages = extension = .txt mime = text/plain words = 6146 sentences = 332 flesch = 43 summary = title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontane-ous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. cache = ./cache/cord-345381-9cckppk2.txt txt = ./txt/cord-345381-9cckppk2.txt === reduce.pl bib === id = cord-344714-0cam9ipf author = Russo, Maria title = Roles of flavonoids against coronavirus infection date = 2020-07-28 pages = extension = .txt mime = text/plain words = 8395 sentences = 394 flesch = 46 summary = Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL(pro), 3CL(pro), NTPase/helicase. Inhibition of TMPRSS2 and Furin protease activities can be considered an interesting therapeutic option against coronavirus infection, especially COVID-19, allowing the block and/or prevention of SARS-CoV-2 infection, as recently reported [28] . Based on these observations, it is not surprising that molecular docking approach, summarized in Fig. 3 , supports the role of flavonoids in the inhibition of SARS-CoV 3CL pro by binding His41 and Cys145 of the catalytic site and other active site residues (e.g., Met49, Gly143, His163, His164, Glu166, Pro168, and Gln89), stimulating their validation by in vitro and in vivo studies. cache = ./cache/cord-344714-0cam9ipf.txt txt = ./txt/cord-344714-0cam9ipf.txt === reduce.pl bib === id = cord-348384-8cvt1fo6 author = Butsashvili, M. title = Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population date = 2020-05-19 pages = extension = .txt mime = text/plain words = 1988 sentences = 120 flesch = 54 summary = This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus and perceptions of preventive measures among the Georgian population, including health care workers (HCWs). We collected information on demographic data (age, gender, marital status, education, employment status), knowledge of symptoms and transmission modes of coronavirus, perceived differences between coronavirus and influenza, availability of antiviral medication and vaccination. In response to the question "Are you afraid of getting infected with SARS-COV-2?" almost half of study participants (46.3%) said "no." The majority of survey respondents correctly identified the transmission route and symptoms of the new coronavirus (96.9% and 98.0%, respectively). cache = ./cache/cord-348384-8cvt1fo6.txt txt = ./txt/cord-348384-8cvt1fo6.txt === reduce.pl bib === id = cord-349117-xfir3m5p author = Hyseni, Inesa title = Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date = 2020-09-10 pages = extension = .txt mime = text/plain words = 8298 sentences = 403 flesch = 52 summary = After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody. cache = ./cache/cord-349117-xfir3m5p.txt txt = ./txt/cord-349117-xfir3m5p.txt === reduce.pl bib === id = cord-348821-2u6ki9dv author = Xu, Ping title = Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. date = 2020-03-10 pages = extension = .txt mime = text/plain words = 3329 sentences = 209 flesch = 51 summary = The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases. https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection cache = ./cache/cord-348821-2u6ki9dv.txt txt = ./txt/cord-348821-2u6ki9dv.txt === reduce.pl bib === id = cord-345929-z7yfegr5 author = Thakur, Suman S. title = Proteomics and Its Application in Pandemic Diseases date = 2020-11-06 pages = extension = .txt mime = text/plain words = 1355 sentences = 94 flesch = 39 summary = found that the antimalarial drug metaquine and anti-HIV antiretroviral saquinavir interact with four SARS-CoV-2 receptors, including Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S protein), interacting with human ACE2; therefore, they may be repurposed for COVID-19 treatment. Furthermore, Maffucci and Contini used an in silico approach to find drug candidates against the main proteinase and spike protein of SARS-CoV-2. suggested that the antigenic peptides generated from the S1 spike glycoprotein of SARS-CoV-2 using aminopeptidases ERAP1, ERAP2, and IRAP might be helpful in selecting better epitopes for immunogenic studies and the design of a vaccine for COVID-19. Interestingly, a computational method was used to find an allosteric site on the SARS-CoV-2 spike protein by Di Paola et al., as its detection would weaken the spike−ACE2 interaction and thereby reduce the viral infection. cache = ./cache/cord-345929-z7yfegr5.txt txt = ./txt/cord-345929-z7yfegr5.txt === reduce.pl bib === id = cord-348301-bk80pps9 author = Wahl, Angela title = Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 date = 2020-09-24 pages = extension = .txt mime = text/plain words = 4279 sentences = 238 flesch = 47 summary = Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Human lung tissues of LoM were inoculated with SARS-CoV-2 and titers of replication competent virus determined 2, 6, and 14 days post-exposure (Fig. 1c , Extended Data Table 2 ). Collectively, our results indicate that LoM re ect the pathogenic effects in icted by SARS-CoV-2 on the human lung and demonstrate their utility as a single in vivo platform to evaluate and compare the replication and pathogenesis of past, present, and future pre-emergent, epidemic, and pandemic coronaviruses accelerating the development and testing of pre-exposure prophylaxis agents such as EIDD-2801. cache = ./cache/cord-348301-bk80pps9.txt txt = ./txt/cord-348301-bk80pps9.txt === reduce.pl bib === id = cord-347460-9vechh4x author = Chang, Feng-Yee title = Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date = 2020-06-04 pages = extension = .txt mime = text/plain words = 8050 sentences = 384 flesch = 43 summary = Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] . cache = ./cache/cord-347460-9vechh4x.txt txt = ./txt/cord-347460-9vechh4x.txt === reduce.pl bib === id = cord-348899-vynk8q8c author = Jo, Seri title = Inhibition of SARS-CoV 3CL protease by flavonoids date = 2019-11-14 pages = extension = .txt mime = text/plain words = 3989 sentences = 236 flesch = 54 summary = A synthetic peptide labelled with an Edans-Dabcyl FRET (Fluorescence resonance energy transfer) pair 12 was used to search SARS-CoV 3CLpro inhibitory compounds against a flavonoid library. The proteolytic assay using the SARS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The three compounds showed the severely reduced fluorescent intensity and thus represented their SARS-CoV 3CLpro inhibitory activity. The interactions between SARS-CoV 3CLpro and three inhibitory flavonoids were analysed to predict their binding affinities. We have created a library of flavonoids to systematically investigate SARS-CoV 3CLpro inhibitory compound by a FRET method. Herbacetin, rhoifolin and pectolinarin were the best inhibitory compounds against SARS-CoV 3CLpro in the flavonoid library. In order to predict the flavonoid scaffolds needed to interact with the catalytic site of SARS-CoV 3CLpro, an induced-fit docking study was performed and analysed. cache = ./cache/cord-348899-vynk8q8c.txt txt = ./txt/cord-348899-vynk8q8c.txt === reduce.pl bib === id = cord-349643-jtx7ni9b author = Uyeki, Timothy M. title = Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus date = 2016-07-17 pages = extension = .txt mime = text/plain words = 4805 sentences = 200 flesch = 31 summary = Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection cache = ./cache/cord-349643-jtx7ni9b.txt txt = ./txt/cord-349643-jtx7ni9b.txt === reduce.pl bib === id = cord-346777-zmmnn9b2 author = Lester, Sandra title = Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies date = 2019-09-11 pages = extension = .txt mime = text/plain words = 5372 sentences = 256 flesch = 44 summary = title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. These results demonstrate that the MERS-CoV-S protein pseudotyped VSV particle-based neutralization assay would serve as a safe, reliable and highly specific alternative method to detect MERS-CoV neutralizing antibodies to be used for future sero-epidemiological studies. A laboratory-confirmed SARS-CoV patient serum sample and a panel of human sera with confirmed high neutralizing antibody titres to human coronaviruses 229E, HKU1, OC43 and NL63 were used in this study to evaluate the VSV-MERS-CoV-S particle-based neutralization assay for potential cross-neutralization. cache = ./cache/cord-346777-zmmnn9b2.txt txt = ./txt/cord-346777-zmmnn9b2.txt === reduce.pl bib === id = cord-345356-gn1iwis0 author = Glebov, Oleg O. title = Understanding SARS‐CoV‐2 endocytosis for COVID‐19 drug repurposing date = 2020-06-02 pages = extension = .txt mime = text/plain words = 3502 sentences = 175 flesch = 35 summary = Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS‐CoV‐2 infection needs to consider the diversity of endocytic pathways available for SARS‐CoV‐2 entry in the human lung epithelium. Taken together, the above evidence suggests that SARS-CoV-2 may employ distinct endocytic pathways for cell entry in the upper and lower respiratory tract (Fig. 1) . This approach would allow tracking of the virus in relation to other endocytic pathways and also to investigate the effect of viral infection on the general membrane trafficking network of the host cell. Taken together, the combination of adequate cell models with the newly developed SARS-CoV-2 toolkit and established tools of membrane trafficking research is well-poised to deliver a key insight into the mechanisms underlying COVID-19 infection. Furthermore, considering that various viruses may use the same endocytic pathways of the host cell [15] , targeting viral entry at the point of endocytosis holds a more general promise for the development of broad-spectrum antiviral drugs [51] . cache = ./cache/cord-345356-gn1iwis0.txt txt = ./txt/cord-345356-gn1iwis0.txt === reduce.pl bib === id = cord-350015-mg5wiihj author = Chen, Yiyin title = Aging in COVID-19: Vulnerability, immunity and intervention date = 2020-10-31 pages = extension = .txt mime = text/plain words = 7489 sentences = 407 flesch = 47 summary = The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and has caused a profound and yet still unfolding health and socioeconomic impacts. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Therefore, age-associated reduction in type 1 IFN response coupled with direct viral suppression could serve as a critical innate immune mechanism that leads to poor cell mediated immunity and increased vulnerability of older adults against SARS-CoV-2 infection with therapeutic implication (Sallard et al., 2020) . On the other hand, children with COVID-19 manifested lower levels of T cell activation than adult COVID-19 patients (Moratto et al., 2020) , suggesting better immune system control and regulation in response to SARS-CoV-2 infection in children. cache = ./cache/cord-350015-mg5wiihj.txt txt = ./txt/cord-350015-mg5wiihj.txt === reduce.pl bib === id = cord-350505-uh8r2vyz author = Kalantar-Zadeh, Kourosh title = Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles date = 2020-05-01 pages = extension = .txt mime = text/plain words = 2343 sentences = 145 flesch = 38 summary = [Image: see text] The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. 2 Therefore, the elucidation of host cytokine molecular pathways and microbiota components 17 as well as bacterial reactions in association with cytokine responses may provide novel microbiome-based therapeutic approaches to SARS-CoV-2 infection. Considering the presented discussion, nutritional and dietary strategies directed at restoring the well-known beneficial microbiota, which can possibly suppress viral infection in the elderly and those with underlying health problems, may be an effective strategy to mitigate the harmful effects of this virus. One approach, as a whole and to be undertaken prior to any viral infection, could include strengthening the intestinal barrier against pathogens, increasing intestinal motility, and reducing an underlying pro-inflammatory state by adopting a Many different direct or indirect microbiome pathways could contribute to SARS-CoV-2-gut interactions. cache = ./cache/cord-350505-uh8r2vyz.txt txt = ./txt/cord-350505-uh8r2vyz.txt === reduce.pl bib === id = cord-347767-aq9niccc author = Zhao, Jie title = Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a date = 2020-06-19 pages = extension = .txt mime = text/plain words = 3538 sentences = 198 flesch = 49 summary = The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. To characterize the effect of herbal medicine, immune function, and inflammatory agents, levels of white blood cells were detected for all patients according to the manufacturer's instructions at the beginning and at the end of the two weeks. In conclusion, our study suggests that the 5th edition recommendation's CM prescription, can be safely used in the treatment of severe pneumonia of SARS-COV-2 with yidu-toxicity blocking lung syndrome. cache = ./cache/cord-347767-aq9niccc.txt txt = ./txt/cord-347767-aq9niccc.txt === reduce.pl bib === id = cord-349682-kpg0vley author = Ojha, Probir Kumar title = Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to date = 2020-09-02 pages = extension = .txt mime = text/plain words = 7923 sentences = 416 flesch = 49 summary = For example, the broad-spectrum antiviral drug Arbidol recently entered the clinical trial for the treatment of SARS-CoV-2 which may act by inhibiting virus-host cell fusion, thus preventing the viral entry into host cells against influenza virus [37] [38] [39] . Smith and Smith [22] analyzed 8000 small drug molecules and natural products (SWEETLEAD library database) employing restrained temperature replica-exchange MD simulations combining virtual screening through the ensemble docking to identify the effective drug for COVID-19 which might stop the virus by two ways: (a) disrupting S protein and ACE2 receptor interface stability; or (b) by troubling the capability of the S protein to recognize Table 2 Pharmacological safety data of selected potential drug candidates [11, 12, 14, 34, 38, 39, 43-45, 57-59, 64, 69, 70, 89] Drug Dose Drug-drug interaction Toxicity Chloroquine phosphate (Aralen) [11, 12, 14, 43, 89] This is a genetically engineered vaccine candidate with the replicationdefective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein. cache = ./cache/cord-349682-kpg0vley.txt txt = ./txt/cord-349682-kpg0vley.txt === reduce.pl bib === id = cord-350557-7i7122zi author = Rawlings, Stephen A title = No Evidence of SARS-CoV-2 Seminal Shedding Despite SARS-CoV-2 Persistence in the Upper Respiratory Tract date = 2020-08-07 pages = extension = .txt mime = text/plain words = 1750 sentences = 115 flesch = 57 summary = We evaluated the presence and level of SARS-CoV-2 RNA in semen, nasal secretion, and saliva collected after confirmed infection. SARS-CoV-2 RNA was not detected in semen 6–17 days after the onset of symptoms despite concomitant shedding in oral secretions. Here, we evaluated the presence and level of SARS-CoV-2 in paired semen, nasal secretion, and saliva samples collected in the short and medium term after confirmed SARS-CoV-2 symptomatic infections. Before enrollment, 5/6 participants tested positive for SARS-CoV-2 RNA on NP swab samples collected within 1-3 days following the onset of symptoms. Upon enrollment in the study, the diagnosis of active SARS-CoV-2 infection was confirmed by positive PCR on NP swab on day 6 post-symptom onset. We found no evidence of SARS-CoV-2 in semen collected 6-17 days after the onset of symptoms despite all men having concomitant shedding of virus in oral secretions up to 792 copies/µL. cache = ./cache/cord-350557-7i7122zi.txt txt = ./txt/cord-350557-7i7122zi.txt === reduce.pl bib === id = cord-350352-wgppovfx author = Temmam, Sarah title = Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus date = 2020-08-29 pages = extension = .txt mime = text/plain words = 2470 sentences = 125 flesch = 54 summary = In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. We investigated the presence of SARS-CoV-2 infection of domestic cats (n = 9) and dogs (n = 12) living in close contact with a cluster of French veterinary students, their owners (n = 18), whose median age was 23 years (21-28 years). Although based on a small cluster of 21 domestic pets, our cross-sectional study based on the antibody response one month after exposure to the index case points to J o u r n a l P r e -p r o o f Journal Pre-proof undetectable interspecific transmission of the SARS-CoV-2 virus between COVID-19 patients and domestic dogs or cats under natural exposure conditions. cache = ./cache/cord-350352-wgppovfx.txt txt = ./txt/cord-350352-wgppovfx.txt === reduce.pl bib === id = cord-350737-nrtrhq1f author = Chen, Xinchun title = Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome date = 2004-04-01 pages = extension = .txt mime = text/plain words = 3474 sentences = 133 flesch = 50 summary = A virus from the family Coronaviridae, termed "SARS coronavirus" (SARS CoV), has been identified as the cause [2] [3] [4] [5] [6] [7] , and criteria for laboratory confirmation of SARS CoV infection have been provided by WHO, on the basis of the following methods: (1) detection of SARS CoV RNA by reversetranscription polymerase chain reaction (RT-PCR); (2) serological detection of SARS CoV-related antibody; and (3) isolation of SARS CoV by cell culture [4] . Using an indirect immunofluorescence assay and parallel acute and convalescent serum samples obtained from patients with SARS, tested for IgG antibody to SARS CoV, Peiris et al. In addition, our results indicated that 9 (25.0%) of 36 patients with probable SARS CoV infection had not produced detectable anti-SARS CoV antibody by day 21 after the onset of fever; this implies that 25.0% of patients with SARS might be misdiagnosed by the laboratory confirmation guidelines that WHO currently recommends [5] . cache = ./cache/cord-350737-nrtrhq1f.txt txt = ./txt/cord-350737-nrtrhq1f.txt === reduce.pl bib === id = cord-350855-gofzhff7 author = Hou, Yixuan J. title = SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract date = 2020-05-27 pages = extension = .txt mime = text/plain words = 3416 sentences = 222 flesch = 50 summary = High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. We measured the relative infectivity of the SARS-CoV-2 GFP virus in primary 283 cells based on the average peak titers and observed that infectivity exhibited the same 284 pattern as the ACE2 expression levels from the upper to lower respiratory tract ( Figure 285 6Bi-6Biv). Gene 1230 expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human 1231 airway epithelial cells and lung tissue cache = ./cache/cord-350855-gofzhff7.txt txt = ./txt/cord-350855-gofzhff7.txt === reduce.pl bib === id = cord-347351-emdj66vj author = Kampf, Günter title = Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 date = 2020-09-18 pages = extension = .txt mime = text/plain words = 10283 sentences = 592 flesch = 50 summary = Originating from a single travel-associated primary case from China, the first documented chain of multiple human-to-human transmissions of SARS-CoV-2 outside of Asia allowed a detailed study of transmission events and identified several factors (e.g. cumulative face-toface contact, direct contact with secretions or body fluids of a patient, personal protective equipment) to classify contacts as low or high risk [32] . In the close surrounding of COVID-19 patients in hospitals SARS-CoV-2 RNA is detected more frequently compared to surfaces outside the patient rooms but samples were so far consistently negative for infectious virus. General disinfection of frequently touched surfaces in the public such as shopping carts or door handles is, however, unlikely to add any protective value because even in COVID-19 wards inanimate surfaces were mainly contaminated in the permanent and immediate surrounding of symptomatic patients (detection of viral RNA, not of infectious virus) and only rarely one room away [138] suggesting that the risk to find SARS-CoV-2 on frequently touched surfaces in the public is low. cache = ./cache/cord-347351-emdj66vj.txt txt = ./txt/cord-347351-emdj66vj.txt === reduce.pl bib === id = cord-346539-kxnrf5g5 author = Riggioni, Carmen title = A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 date = 2020-06-14 pages = extension = .txt mime = text/plain words = 15760 sentences = 1112 flesch = 48 summary = This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. The first cases of the coronavirus disease 2019 (COVID19) , caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019 1 and rapidly led to pandemic. 40, 41 A seroconversion study in COVID-19 patients has found and association between disease severity and SARS-CoV-2-specific IgA levels. Mesenchymal stem cell therapy may potentiate the low IFN-I and -III levels and moderate IFN-stimulated gene response reported in SARS-CoV-2-infected ferrets and COVID-19 patients. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial cache = ./cache/cord-346539-kxnrf5g5.txt txt = ./txt/cord-346539-kxnrf5g5.txt === reduce.pl bib === id = cord-349659-6drnriun author = Grant, Benjamin D. title = SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents date = 2020-07-01 pages = extension = .txt mime = text/plain words = 3203 sentences = 207 flesch = 57 summary = title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents In this work, we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. 10 Antigen detecting ELISAs were previously developed in 2004 for SARS-CoV-1, with limits of detection of approximately 50 pg/mL and clinical sensitivity as a function of days since onset that was significantly better than the useful time window for the current generation of SARS-CoV-2 serology assays. A dose response curve was generated for the half-strip LFA using two commercially available SARS-CoV-2 nucleocapsid (N) proteins, from Genemedi and Genscript. Analytical Chemistry pubs.acs.org/ac Article and determination of realistic limits of detection for a full strip LFA in multiple sample matrices will help point the way toward the best approach for an antigen detecting LFA for SARS-CoV-2. In this paper, we present a half-strip LFA for the detection of nucleocapsid protein of SARS-CoV-2. cache = ./cache/cord-349659-6drnriun.txt txt = ./txt/cord-349659-6drnriun.txt === reduce.pl bib === id = cord-349262-gnqbyc6t author = Hemida, Maged Gomaa title = The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) date = 2020-10-14 pages = extension = .txt mime = text/plain words = 3172 sentences = 174 flesch = 62 summary = title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. However, the nasal swabs are still the sample of choice in the diagnosis of MERS-CoV among the infected dromedary camel population. Detection of the virus in the air of positive camel's herd [5, 6] may suggest the virus is excreted in the breath of the infected animals in high concentration. The aim of our study was to test the possibility of MERS-CoV shedding in the breath of the infected dromedary camels. Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Dromedary camels and the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) cache = ./cache/cord-349262-gnqbyc6t.txt txt = ./txt/cord-349262-gnqbyc6t.txt === reduce.pl bib === id = cord-347734-0z2kin6r author = Armann, J. P. title = Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates date = 2020-07-17 pages = extension = .txt mime = text/plain words = 2294 sentences = 138 flesch = 51 summary = title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates However, there is reason to believe that children play a less significant role in SARS-CoV-2 transmission compared to influenza, making control measures focused on this age group less effective: Most countries-including Germany-report a much lower proportion of cases in children compared to their population size 4-6 . The findings from this unique study in older students and their teachers indicate that the prevalence of IgG antibodies against SARS-CoV-2 remains extremely low after the first wave of the corona pandemic in Germany. In fact, 5 of the 12 participants with antibodies against SARS-CoV-2 had a personal or household history of COVID-19, yielding a ratio of unidentified to identified cases of 2.4, which is much smaller than that previously assumed by some authors 9 . cache = ./cache/cord-347734-0z2kin6r.txt txt = ./txt/cord-347734-0z2kin6r.txt === reduce.pl bib === id = cord-353209-qkhfp66l author = Steiner, Daniel J. title = Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date = 2020-06-16 pages = extension = .txt mime = text/plain words = 2517 sentences = 129 flesch = 45 summary = We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. Aminereactive substrates for fabrication of AIR arrays were provided by Adarza BioSystems, Inc. For ELISA assays, SARS-CoV-2 full-length spike and RBD were produced in-house using a mammalian expression system, 20,21 as was influenza A/H1N1/California 2009 hemagglutinin. To that end, we have presented preliminary data on a 15-plex array on the AIR platform, developed in response to the need to study SARS-CoV-2 but incorporating antigens for other coronaviruses and influenza. Responses to SARS-CoV-2 antigens on the array effectively discriminated between serum samples from uninfected and COVID-19 convalescent subjects, with generally good correlation to ELISA data. cache = ./cache/cord-353209-qkhfp66l.txt txt = ./txt/cord-353209-qkhfp66l.txt === reduce.pl bib === id = cord-351169-y91fdf66 author = Phillips, Lia title = Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia date = 2020-09-14 pages = extension = .txt mime = text/plain words = 1732 sentences = 105 flesch = 37 summary = Corticosteroid can be given safely to patients with SARS-CoV-2 presenting with acute respiratory distress syndrome and ALL. Although recommendations are emerging for the general management of oncology patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1,2 there is little experience in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Providers may have concern about initiating multiagent chemotherapy in patients with SARS-CoV-2, particularly corticosteroids, which are an essential part of induction regimens, but raise the theoretical possibility of delayed viral clearance. We describe our experience of successfully initiating therapy for an adolescent diagnosed with ALL, while managing severe SARS-CoV-2 infection marked by respiratory failure, systemic inflammation, and autoimmune hemolytic anemia (AIHA). 1, 2 In this case, intensive remission induction chemotherapy was initially delayed due to concern for potential worsening of SARS-CoV-2 disease by exacerbating the patient's already immunocompromised state in the setting of ALL. cache = ./cache/cord-351169-y91fdf66.txt txt = ./txt/cord-351169-y91fdf66.txt === reduce.pl bib === id = cord-351649-87g7g5au author = Haagmans, Bart L. title = SARS date = 2009-01-30 pages = extension = .txt mime = text/plain words = 6736 sentences = 298 flesch = 40 summary = Because the disease in macaques caused by SARS-CoV infection was pathologically similar to that seen in human patients with SARS, and since the virus should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. African green monkeys immunized via the respiratory tract with two doses of a recombinant Newcastle disease virus encoding the S protein developed a relatively high titer of SARS-CoV neutralizing antibodies and upon challenge demonstrated a 1000-fold zoonotic coronaviruses. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies cache = ./cache/cord-351649-87g7g5au.txt txt = ./txt/cord-351649-87g7g5au.txt === reduce.pl bib === id = cord-350992-l6l24pco author = Roldan, Eugenia Quiros title = The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? date = 2020-05-13 pages = extension = .txt mime = text/plain words = 8037 sentences = 393 flesch = 40 summary = Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. We also propose a different insight into some of CQ and HCQ effects, suggesting a potential role of iron homeostasis in Sars-Cov-2 disease (COVID-19), similarly to several other human viral infections [2] [3] [4] . The search strategy was to use different search terms alone and in any combination, such as "Sars-Cov-2 disease", "COVID-19", "Sars-Cov-2", "coronavirus", "clinical trial", "treatment", "drug", "chloroquine", "hydroxychloroquine", "iron", "virus", "viral entry", "viral spread", "anti-viral activity", "infection", "inflammation", "immunity", "innate immunity", "cytokine", "IL-6", "TNF-", "IL-1", "adaptive immunity", "thrombosis", "in vitro". cache = ./cache/cord-350992-l6l24pco.txt txt = ./txt/cord-350992-l6l24pco.txt === reduce.pl bib === id = cord-350959-bsbz3a1l author = Dovey, Zachary title = Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists date = 2020-06-16 pages = extension = .txt mime = text/plain words = 5079 sentences = 241 flesch = 47 summary = There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes. As shown in Table 2 , PCa patients with either diabetes or hypertension should seek advice from their physicians to optimize their treatment, especially if this includes ACE inhibitors or ARBs [32] , to reduce their risk of SARS-CoV-2 infection and morbidity. Tewari Prostate cancer (PCa) patients may have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. cache = ./cache/cord-350959-bsbz3a1l.txt txt = ./txt/cord-350959-bsbz3a1l.txt === reduce.pl bib === id = cord-352562-qfb478sf author = Yamamoto, Lidia title = SARS-CoV-2 infections with emphasis on pediatric patients: a narrative review date = 2020-09-04 pages = extension = .txt mime = text/plain words = 7315 sentences = 341 flesch = 45 summary = In the section devoted to the specific laboratory diagnosis of COVID-19, the most used RT-PCR protocols were described and some studies on the serological diagnosis with IgA, IgM and IgG detection were detailed, including the use of rapid immunochromatographic assays and discussing the ideal period after the onset of symptoms to perform each type of test. They identified 191 cases in hospitalized patients younger than 21 years of age, reported by hospitals in the New York State with the diagnosis of Kawasaki disease, toxic shock syndrome, myocarditis, and suspected multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The laboratory diagnosis of COVID-19 are based on the detection of viral RNA by real time amplifications (RT-PCR) 40 or the detection of antibodies (immunoglobulins) anti-SARS-CoV-2 from the classes IgM, IgA and IgG, produced by the host's immune system. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review cache = ./cache/cord-352562-qfb478sf.txt txt = ./txt/cord-352562-qfb478sf.txt === reduce.pl bib === id = cord-350451-lf27iuwk author = Benedetti, Francesca title = SARS‐CoV‐2: March toward adaptation date = 2020-07-11 pages = extension = .txt mime = text/plain words = 1212 sentences = 79 flesch = 44 summary = A third factor still subject of debate is how and how much the mutations observed in SARS-CoV-2 provide an indication of viral fitness and adaptation, and their role first into the initial phases of transmission and now during the reduction of viral spreading. The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human pathogen, first detected in China quickly became a global health emergency, culminating with the World Health Organization publicly proclaiming the SARS-CoV-2 outbreak as a pandemic (11 March 2020) . Several reports result show that SARS-CoV-2 is rapidly moving across countries, and new mutation hotspots are emerging in different parts of the genome. Although SARS-CoV-2 is less lethal than MERS-CoV, up to 20% of the infected people develop rapidly a severe disease characterized by interstitial pneumonia and acute respiratory distress syndrome that can ultimately lead to death. Davide Zella http://orcid.org/0000-0001-5576-5770 Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant cache = ./cache/cord-350451-lf27iuwk.txt txt = ./txt/cord-350451-lf27iuwk.txt === reduce.pl bib === id = cord-352909-s11tpfoq author = Sun, Zhiping title = Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions date = 2020-08-14 pages = extension = .txt mime = text/plain words = 1747 sentences = 106 flesch = 66 summary = Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions Zhiping Sun 1 , Xia Cai 1 , Chenjian Gu 2 , Rong Zhang 2 , Wendong Han 1 , Yun Qian 1 , Yuyan Wang 2 , Wei Xu 2 , Yang Wu 2 , Xunjia Cheng 2 , Zhenghong Yuan 2 , Youhua Xie 2 and Di Qu 1, 2 Dear Editor, The pneumonia caused by a novel coronavirus was first reported in December 2019 in Wuhan of China, and since then has become a pandemic 1, 2 . Here, we first investigated the infectivity of SARS-COV-2 using a plaque-purified strain nCoV-SH01 isolated from a patient in Shanghai (GenBank MT121215) 6 , studied subsequently its stability in liquid medium, on dry filter paper, and under acidic condition (pH2.2) at RT. cache = ./cache/cord-352909-s11tpfoq.txt txt = ./txt/cord-352909-s11tpfoq.txt === reduce.pl bib === id = cord-353524-3w970ycx author = Dömling, Alexander title = Chemistry and Biology of SARS-CoV-2 date = 2020-05-22 pages = extension = .txt mime = text/plain words = 3942 sentences = 237 flesch = 52 summary = Given that SARS-CoV-2 and SARS-CoV share very high identical sequence in their 3CLpro, these HIV protease inhibitors are currently again repurposed for the treatment of COVID-19 (Chinese Clinical Trial Registry: ChiCTR2000029539). 30, 31 The interplay of the ACE receptor in cardiovascular diseases (with the well-known drug class of ACE inhibitors) and as the docking point for SARS-CoV-2 cellular infection is a current point of intense debate and research. For example, the crystal structure of SARS-CoV-2 N protein RNA-binding domain was just published and will give structural insight as a potential drug target. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites cache = ./cache/cord-353524-3w970ycx.txt txt = ./txt/cord-353524-3w970ycx.txt === reduce.pl bib === id = cord-352123-0bflqj1c author = Csiszar, Anna title = Companion animals likely do not spread COVID-19 but may get infected themselves date = 2020-08-07 pages = extension = .txt mime = text/plain words = 4752 sentences = 225 flesch = 51 summary = Recent evidence suggests that SARS-CoV-2, similar to other coronaviruses, can infect several species of animals, including companion animals such as dogs, cats, and ferrets although their viral loads remain low. In late March 2020, the Federal Agency for the Safety of the Food Chain (FASFC) in Belgium reported that a pet cat was diagnosed to be infected with SARS-CoV-2 [21, 22] , showing that felines living in the household of people with COVID-19 are at risk of contracting the disease and may potentially spread the virus. On April 23, it was reported that two pet cats in New York state have tested positive for the SARS-CoV-2, which are the first confirmed COVID-19 cases in companion animals in the USA [22] . In the current SARS-CoV-2 pandemic, the situation is rapidly evolving and in the light of the recent evidence, we should be aware of the possibility that humans can be potentially infected with COVID-19 by animals, including by pet cats, dogs, or other domesticated species. cache = ./cache/cord-352123-0bflqj1c.txt txt = ./txt/cord-352123-0bflqj1c.txt === reduce.pl bib === id = cord-351011-v4zmksio author = Golden, Joseph W. title = Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date = 2020-07-09 pages = extension = .txt mime = text/plain words = 4650 sentences = 268 flesch = 52 summary = In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. In comparison with the normal lung architecture in uninfected control animals, infected mice necropsied on day 3, and those succumbing to disease on days 5-11, had varying levels of lung injury including area of lung consolidation characterized by inflammation/expansion of 145 alveolar septa with fibrin, edema and mononuclear leukocytes and infiltration of vessel walls by numerous mononuclear leukocytes (Fig 3A, Fig S4, and Table S1 ). Importantly, in our study some animals at the lower dose survived infection despite significant Infection of K18-hACE2 mice by SARS-CoV-2 produces a disease similar to that observed in acute human cases, with development of an acute lung injury associated with edema, production 285 of inflammatory cytokines and the accumulation of mononuclear cells in the lung. cache = ./cache/cord-351011-v4zmksio.txt txt = ./txt/cord-351011-v4zmksio.txt === reduce.pl bib === id = cord-353293-vjdwh19x author = nan title = Post-COVID-19 global health strategies: the need for an interdisciplinary approach date = 2020-06-11 pages = extension = .txt mime = text/plain words = 3856 sentences = 175 flesch = 36 summary = Gemelli IRCSS (Rome, Italy) has set up a multidisciplinary healthcare service called "Post-COVID-19 Day Hospital." The specialist assessments offered to patients are outlined in the following sections. Furthermore, the important role of geriatrician acting as a care manager of patients who suffered COVID-19 disease is described. A respiratory follow-up is of pivotal importance to evaluate lung function, alveolar-arterial gas exchange, and exercise tolerance in recovered non-infective COVID-19 patients [5] . In this Post-COVID-19 Day Hospital, internal medicine and geriatric specialists are integrated with infectious disease physicians, pneumologists, immuno-rheumatologists, and other specialists into the management of the SARS-CoV-2 infection. As a whole, the post-acute care service at the Fondazione Policlinico Gemelli aims at expanding the knowledge of COVID-19 and its impact on health status and care needs as well as at promoting healthcare strategies to treat and prevent the clinical consequence of SARS-CoV-2 infection across different organs and systems. cache = ./cache/cord-353293-vjdwh19x.txt txt = ./txt/cord-353293-vjdwh19x.txt === reduce.pl bib === id = cord-354398-f3cg8gi1 author = Al-Saud, Haya title = Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing date = 2020-09-20 pages = extension = .txt mime = text/plain words = 4018 sentences = 199 flesch = 55 summary = The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. We validated the modified Invitrogen Forensic DNA Purification kit in extracting in-laboratory propagated SARS-COV-2 RNA by conducting manual and automated extractions on titrations from 15 000 copies to 60 copies of SARS-COV-2 followed by RT-qPCR methods: the commercially available TaqPath One-Step qRT-QP-CR kit (using the N, S, and ORF1b genes) and primers and probes from Metabion, Germany to establish an inhouse RT-qPCR assay based on E, RdRp2 and RdRp4 gene detection as per recommended SARS-COV-2 testing from CDC and WHO. cache = ./cache/cord-354398-f3cg8gi1.txt txt = ./txt/cord-354398-f3cg8gi1.txt === reduce.pl bib === id = cord-354597-xubsodnk author = Carvalho, Alexandre title = SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease date = 2020-04-17 pages = extension = .txt mime = text/plain words = 2779 sentences = 159 flesch = 47 summary = Recent reports from China have described concomitant digestive symptoms, such as nausea, vomiting, diarrhea, and abdominal pain, in patients with confirmed SARS-CoV-2 pulmonary infection (5) (6) (7) (8) and the presence of SARS-CoV-2 RNA in fecal samples (8, 9) . We present a case of SARS-CoV-2 gastrointestinal infection causing acute hemorrhagic colitis and signaling COVID-19 disease which endoscopy confirmed colonic injury and helped exclude other etiologies of disease. On hospital day 4, 9 days after the onset of her digestive symptoms, the patient developed a cough; nasopharyngeal swabs were sent for comprehensive viral detection, including SARS-CoV-2 RNA (Quest Diagnostics). Given the patient's elevated C-reactive protein and persistent abdominal pain and bloody diarrhea, a flexible sigmoidoscopy was performed on hospital day 4 to evaluate for evidence of inflammatory bowel disease or ischemic colitis. cache = ./cache/cord-354597-xubsodnk.txt txt = ./txt/cord-354597-xubsodnk.txt === reduce.pl bib === id = cord-351525-306syrrn author = Yang, Yong-Le title = Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission date = 2019-11-26 pages = extension = .txt mime = text/plain words = 6911 sentences = 306 flesch = 53 summary = title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. As a brief summary of the results, 21 of the 24 cell lines showed significant susceptibility to SADS-CoV infection, defined by efficient viral replication, antigen expression, and the appearance of cytopathic effect (CPE). As some cells did not display CPE after SADS-CoV infection, all cell lines were subsequently tested for viral M protein expression by immunofluorescence assay (IFA) Fig. 1) , revealing the same range as seen by CPE in the different cell lines (data not shown). cache = ./cache/cord-351525-306syrrn.txt txt = ./txt/cord-351525-306syrrn.txt === reduce.pl bib === id = cord-354394-zojhdnlu author = Wang, Wei-Kung title = Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis date = 2004-07-17 pages = extension = .txt mime = text/plain words = 3972 sentences = 175 flesch = 56 summary = We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis. Using a quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay and fractionation experiment, we investigated the load of SARS-CoV in these samples and different components of the throat wash. As shown in Table 1 , SARS-CoV RNA was detected in the cell-associated component of the throat wash from all 16 specimens examined. cache = ./cache/cord-354394-zojhdnlu.txt txt = ./txt/cord-354394-zojhdnlu.txt === reduce.pl bib === id = cord-356166-fpno9zg5 author = Miyakawa, Kei title = Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles date = 2020-09-15 pages = extension = .txt mime = text/plain words = 1548 sentences = 94 flesch = 52 summary = title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles However, a simple, convenient, rapid, and high-throughput test capable of directly detecting nAbs with high specificity, which could act as an ideal alternative to the neutralization assay, is yet to be developed (Ozcurumez et al., 2020) . In this report, we have developed a HiBiT-VLP-based neutralization test (hiVNT) that can readily detect SARS-CoV-2 nAbs ( Figure 1A ). We noticed a robust increase in NanoLuc activity when the LgBiT-expressing We next tested whether our newly developed hiVLP-SARS2 system could detect nAbs in the serum of COVID-19 patients. In this study, we established the hiVNT, a simple, high-throughput assay system for the quantitative and rapid determination of SARS-CoV-2 nAbs in the sera of individuals after recovery from symptomatic or subclinical COVID-19. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells cache = ./cache/cord-356166-fpno9zg5.txt txt = ./txt/cord-356166-fpno9zg5.txt === reduce.pl bib === id = cord-351115-dy81dtnk author = Wang, Chen title = Identification of evolutionarily stable sites across the SARS-CoV-2 proteome date = 2020-10-20 pages = extension = .txt mime = text/plain words = 6133 sentences = 310 flesch = 50 summary = This study addresses both by utilizing evolutionary information from SARS-CoV-2 sequence and structural data to search for actionable functional sites for each protein in the SARS-CoV-2 genome. Here we systematically suggest potential drug target sites for most SARS-CoV-2 proteins based on evolutionary information. This relative ranking re ects the variation entropy of each sequence position within and across the branches of an associated phylogenetic tree, revealing evolutionary pressure points that correspond to functional and structural determinants, and the protein sites at which they often cluster (30) . As in our approach to discover ET drug sites, we combined ET residue ranking information with sequencing data from SARS-CoV-2 isolates to arrive at linear peptides along the proteome that are evolutionarily important and also show little variation in the current outbreak ( Figure S6 , Dataset S5). The data include, for example, multiple sequence alignments, precalculated ET ranks, and predicted epitopes (both linear and structural) for all SARS-CoV-2 proteins. cache = ./cache/cord-351115-dy81dtnk.txt txt = ./txt/cord-351115-dy81dtnk.txt === reduce.pl bib === id = cord-353777-t8q99tlq author = Jia, Yong title = Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date = 2020-04-11 pages = extension = .txt mime = text/plain words = 3217 sentences = 180 flesch = 58 summary = The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. The discrepant phylogenies for the spike protein and its 23 receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARSDespite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that 25 leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27 th January 2020 from 26 cache = ./cache/cord-353777-t8q99tlq.txt txt = ./txt/cord-353777-t8q99tlq.txt === reduce.pl bib === id = cord-353704-lfndq85x author = Ye, Zi-Wei title = Zoonotic origins of human coronaviruses date = 2020-03-15 pages = extension = .txt mime = text/plain words = 8096 sentences = 434 flesch = 54 summary = In contrast, SARS-CoV, MERS-CoV and the newly-identified SARS-CoV-2 are highly pathogenic, causing severe lower respiratory tract infection in relatively more patients with a higher chance to develop acute respiratory distress syndrome (ARDS) and extrapulmonary manifestations. The 2019 novel HCoV (2019-nCoV), which has subsequently been renamed SARS-CoV-2, is the causative agent of the ongoing epidemic of coronavirus disease 2019 (COVID19) , which has claimed more than 3,120 lives and infected more than 91,000 people as of March 3, 2020 [19] . All these four communityacquired HCoVs have been well adapted to humans and are generally less likely to mutate to cause highly pathogenic diseases, though accidents did occur for unknown reasons as in the rare case of a more virulent subtype of HCoV-NL63, which has recently been reported to cause severe lower respiratory tract infection in China [38] . Alternatively, whereas bat alpha-CoVs serve as the gene pool of HCoV-229E, alpacas and dromedary camels might serve as intermediate hosts that transmit viruses to humans, exactly as in the case of MERS-CoV [69] . cache = ./cache/cord-353704-lfndq85x.txt txt = ./txt/cord-353704-lfndq85x.txt === reduce.pl bib === id = cord-353826-owoec2ud author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-07-27 pages = extension = .txt mime = text/plain words = 5496 sentences = 269 flesch = 53 summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Analysis of SARS-CoV-2 S proteinspecific murine splenocyte responses by IFN-γ ELISpot assay showed no statistically significant difference between the primeonly and prime-boost vaccination regimens, in either strain of mouse (Fig. 1a) . SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 prime-only and prime-boost vaccination regimens in mice and pigs SARS-CoV-2 S protein-specific antibody titres in serum were determined by ELISA using recombinant soluble trimeric S (FL-S) and receptor binding domain (RBD) proteins. Small animal models have variable success in predicting vaccine efficacy in larger animals but are an important To analyse SARS-CoV-2 S-specific T cell responses, all mice were sacrificed on day 49 for isolation of splenocytes and pigs were blood sampled longitudinally to isolate PBMC. cache = ./cache/cord-353826-owoec2ud.txt txt = ./txt/cord-353826-owoec2ud.txt === reduce.pl bib === id = cord-355567-60sfv60p author = Azuma, Kenichi title = Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control date = 2020-11-03 pages = extension = .txt mime = text/plain words = 9229 sentences = 436 flesch = 42 summary = Recently, 36 researchers insisted on the potential risk of indoor airborne transmission of SARS-CoV-2 and the importance of sufficient and effective ventilation, particle filtration, and air sterilization as infection control measures inside buildings [43] . Therefore, the MHLW published a document titled "Prevention of the COVID-19 Clusters" Abbreviation: SARS-CoV severe acute respiratory syndrome coronavirus Fig. 1 Traditional Japanese office building HVAC systems: a a centralized HVAC system; and b a centralized ventilation system with an individual air-conditioning system on March 1, 2020 [94] , showing the need for adequate ventilation in buildings because a ventilation standard for infection control has not been established in general buildings in Japan and the characteristics of indoor spaces where the clusters occurred might include poor ventilation and crowding. cache = ./cache/cord-355567-60sfv60p.txt txt = ./txt/cord-355567-60sfv60p.txt === reduce.pl bib === id = cord-352230-8mazd3eu author = Beeraka, Narasimha M. title = Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date = 2020-09-18 pages = extension = .txt mime = text/plain words = 9394 sentences = 543 flesch = 40 summary = Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. COVID-19 is a devastating disease caused by a coronavirus related to the one that caused outbreaks of Severe Acute Respiratory Syndrome (SARS) in the year 2002 (1, 2) . cache = ./cache/cord-352230-8mazd3eu.txt txt = ./txt/cord-352230-8mazd3eu.txt === reduce.pl bib === id = cord-353484-q7d0ysbo author = Liu, Xue title = COVID-19: Progress in diagnostics, therapy and vaccination date = 2020-06-19 pages = extension = .txt mime = text/plain words = 8557 sentences = 465 flesch = 41 summary = Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic. Another type of rapid diagnostic test (RDT) that detects the presence of viral antigens expressed by SARS-CoV-2 virus in a respiratory tract sample is of low complexity and may provide results typically within 30 minutes [68, 69] . Studies in Vero E6 cells have suggested that favipiravir can cripple the SARS-CoV-2 virus (EC50 = 61.88 μM) [88] , and patients with COVID-19 are being recruited in randomized trials to evaluate the efficacy of favipiravir plus other antivirals (e.g., ClinicalTrials.gov: ChiCTR2000029600, ChiCTR2000029544). As no specific therapeutic agents or vaccines are available for COVID-19, this therapy is the only strategy that is immediately available for use to prevent and treat a novel, emerging infectious disease such as SARS-CoV-2 infection [121, 122] . cache = ./cache/cord-353484-q7d0ysbo.txt txt = ./txt/cord-353484-q7d0ysbo.txt === reduce.pl bib === id = cord-353392-rqeultbq author = Kumar, Govindarajan Venkat title = A short review on antibody therapy for COVID-19 date = 2020-04-20 pages = extension = .txt mime = text/plain words = 1944 sentences = 105 flesch = 48 summary = Abstract The beginning of the novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). The third outbreak of severe illness caused by the novel SARS-CoV-2 coronavirus (COVID-19) that emerged in the Wuhan city, China, is pandemic and spread to more than 200 countries [5, 6, 7] . Based on the previous studies and reports in treating other coronaviruses such as SARS and MERS, the early administration of convalescent plasma from patients that contains raised antibodies can possibly reduce the spreading of infection and mortality [19, 20, 21, 22] . reported that the convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with SARS-CoV-2 infections. After getting approval from the ethical committee, Shenzhen, Third People's Hospital, they administrated convalescent plasma containing neutralizing antibodies to 5 critically ill patients with SARS-CoV-2. cache = ./cache/cord-353392-rqeultbq.txt txt = ./txt/cord-353392-rqeultbq.txt === reduce.pl bib === id = cord-354824-7fdcu2f0 author = Wu, Renyi title = An Update on Current Therapeutic Drugs Treating COVID-19 date = 2020-05-11 pages = extension = .txt mime = text/plain words = 9652 sentences = 504 flesch = 42 summary = Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. This estimated 20% of patients developing more severe disease with SARS-CoV-2 infection are most likely due to genetics, epigenetics, and or other factors, with dampened innate immune response to fight the virus coupled with enhanced viral load leading to cytokine storm, severe inflammatory/oxidative stress response, and severe lung injury secondary to ARDS. Chloroquine can inhibit the entry of SARS-CoV-2 and prevent virus-cell fusion by interfering with glycosylation of ACE2 receptor and its binding with spike protein, suggesting that chloroquine treatment might be more effective in the early stage of infection, before COVID-19 reduces ACE2 expression and activity [30, 38, 39] . Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, doubleblinded, phase IIb clinical trial (CloroCovid-19 Study) cache = ./cache/cord-354824-7fdcu2f0.txt txt = ./txt/cord-354824-7fdcu2f0.txt === reduce.pl bib === id = cord-356009-emn2w8if author = Roshandel, M. R. title = What Specimen Urologists Should Be Most Concerned About ? A Systematic Review and Meta-Analysis date = 2020-10-13 pages = extension = .txt mime = text/plain words = 4687 sentences = 292 flesch = 49 summary = Conclusions: Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight ?percent of patients but also its incidence may have associations with the severity of the ?systemic disease, ICU admission, and fatality rates. The searches included medical subject headings (MeSH) and keywords for SARS-CoV-2, COVID, Corona, together with shedding, persistence, urine, urinary, specimen, viral load, or RNA body fluids. We completed the data abstraction process using created forms to record study characteristics, clinical data, and laboratory data including study year and design, country of study origin, total initial population size, test type for disease diagnosis, test type for samples (urine/stool/rectal swab/blood), patients age (including mean and range), number of positive and total patients and/or (wherever applicable) number of positive and total specimens collected for each test category, disease severity, ICU admission, and fatality rate. cache = ./cache/cord-356009-emn2w8if.txt txt = ./txt/cord-356009-emn2w8if.txt === reduce.pl bib === id = cord-350903-nwagvvc5 author = Softic, Laurent title = Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025) date = 2020-06-23 pages = extension = .txt mime = text/plain words = 1398 sentences = 80 flesch = 47 summary = Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC(50)) of 0.46 ± 0.04 μM. For instance, chloroquine has been shown to bear potent antiviral properties against SARS-CoV-2 in vitro, and several clinical trials are under way to assess its efficacy in patients with COVID-19. Cyclosporine A (CsA), a potent cyclophilin inhibitor, blocks the replication of various coronaviruses in vitro, including HCoV-229E, HCoV-NL63, FPIV, mouse hepatitis virus (MHV), avian infectious bronchitis virus, and SARS-CoV (5, (8) (9) (10) . The antiviral effectiveness of increasing concentrations of alisporivir was measured in Vero E6 cells infected with a clinical isolate of SARS-CoV-2 at a multiplicity of infection (MOI) of 0.02 (Fig. 1A) . These results justify rapidly conducting a proof-of-concept phase 2 trial to assess the antiviral properties and the effect of alisporivir on COVID-19 clinical outcomes in infected patients. cache = ./cache/cord-350903-nwagvvc5.txt txt = ./txt/cord-350903-nwagvvc5.txt ===== Reducing email addresses cord-009476-4emc4o6n cord-267770-ik1ib3zb cord-269289-6uog10j4 cord-277487-jgbjxgh1 cord-284589-j1609xlu cord-303216-1pbuywz6 cord-303297-fiievwy7 cord-309418-dx6e0lri cord-311762-f6muhf3d cord-310221-car394ou cord-311114-ggcpsjk8 cord-312305-ll29frwc cord-319194-ukuia48s cord-315288-fcx4q6mp cord-321166-nvphu1fm cord-327997-noqbcxua cord-326013-5i35zdmv cord-331193-33cyvidx cord-333498-d25qfq0f cord-337105-jlmh79qv cord-350855-gofzhff7 Creating transaction Updating adr table ===== Reducing keywords cord-024133-zv0ysi8m cord-025119-201ac32t cord-029813-o2uzcuai cord-124012-5zxkd2jy cord-031079-9lxhvyyb cord-009476-4emc4o6n cord-257399-p6of5fno cord-193489-u6ewlh16 cord-029112-u507i0t0 cord-158628-71n1tgrw cord-015503-j99cgsjt cord-252389-xrdbmosj cord-032751-pmclolvh cord-019048-29wzpwvr cord-254446-yxqbe1dj cord-033551-eojpkxz9 cord-032222-i6gfp4me cord-150183-zzzyewjb cord-031289-uxoz0xhk cord-256146-d599uera cord-253457-gawn4s9g cord-254636-3lr008th cord-253844-y6xdcf20 cord-252600-bvh1o64r cord-104500-m0kfom0x cord-252767-as841xo0 cord-256508-ce59ovan cord-193133-puqcbf8t cord-033780-184e64tr cord-256888-tdx12ccj cord-252232-vgq6gjpx cord-029547-9ei1ram3 cord-256020-wrui3i2l cord-253905-zknmfgsh cord-252049-rgdynmla cord-024317-w1ep0wq8 cord-030934-t7akdu6x cord-258268-7ypq0t3d cord-254395-tu4aqczj cord-256217-fnjer0e0 cord-256737-ptjng78b cord-214854-ck61ja2t cord-253862-jl1zhg13 cord-255997-oer5lxxr cord-259229-e8m8m4ut cord-258881-74aijckl cord-255883-mz6nyisw cord-255815-5d9bqji0 cord-255552-k1retwa4 cord-034354-4xu97je3 cord-254968-czrgzyr3 cord-259603-bh198xgl cord-254469-7q6xi2xx cord-257958-yehnlabq cord-258914-g6pv8zz9 cord-258595-bk35vxlr 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cord-270550-if748w2n cord-269289-6uog10j4 cord-270533-s2d3q4ob cord-269275-b7xxk48t cord-274399-cd7cmpoj cord-271243-8cfyen86 cord-268718-tt07cwrf cord-268388-kkhuzf3p cord-271781-cfv0ta10 cord-272113-j82z4q8x cord-271648-m2c5bvuj cord-272010-kc0gi3cj cord-268540-wrjzr3ws cord-271505-eot38721 cord-272603-nbosceoz cord-272654-hh29olk7 cord-273451-xnce010o cord-274141-vujx538o cord-274506-fzcuu4ma cord-275138-033r259v cord-268206-ino9srb6 cord-274122-n9jnu2ah cord-275454-an8xvow3 cord-275565-xerr4vki cord-273182-djb0ozrt cord-268561-vq1uhj5i cord-274834-24v2b509 cord-274841-rcdoewwv cord-275313-mfyff9ne cord-275252-4e3cn50u cord-275926-rj23z7po cord-274396-l611eisi cord-275946-ofd2ipvs cord-278522-e4qa19o6 cord-277841-7sp8ftbc cord-277487-jgbjxgh1 cord-279443-2e4gz2bo cord-275690-83nrzfon cord-280662-gakayv6e cord-278362-pwi48i20 cord-274802-7ioiwsd8 cord-277253-vy0mvzeb cord-276630-qci7khki cord-278370-fuu20ae7 cord-277399-0w8is9xm cord-280068-rszu1c48 cord-278618-7tu5c7m1 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cord-304263-5kddk5fa cord-305704-grzrkff9 cord-304792-8sdxqmkb cord-302707-cap2rgf7 cord-305931-0pgu2gvh cord-304073-f3iwclkm cord-303741-1ou0cy5k cord-303297-fiievwy7 cord-304479-uxp1kg86 cord-304306-rxjahqwh cord-301730-flv5lnv8 cord-304418-k9owyolj cord-304295-3mpymd8a cord-305587-xtqvtleb cord-303517-8971aq02 cord-306581-g3d0lqxp cord-306373-61snvddh cord-308342-ycdok8fc cord-308110-cco3aq4n cord-306177-5wefp31y cord-305856-xt3zxajf cord-304617-5ozf18lg cord-308857-otsrexqu cord-307701-fujejfwb cord-308252-qwoo7b1l cord-307860-iqk1yiw4 cord-309289-vm0k7hfx cord-309074-pys4aa60 cord-310807-p5cb6idp cord-309418-dx6e0lri cord-299093-zp07aqpm cord-309147-c3ikb81g cord-307489-2liu4anc cord-309633-1cd74xdl cord-310239-mmvuij3k cord-311762-f6muhf3d cord-309138-44qpk2vf cord-310017-c8rd714a cord-308945-i2agpvhk cord-308583-vtmwv8zl cord-310507-5h6egve4 cord-310221-car394ou cord-309474-9h9w46eq cord-311125-v9ddes3c cord-311214-eqwxkwqa cord-313344-rqvi2ksc cord-310624-3kojrkz7 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size in words: 4,882 average readability score: 48 nouns: patients; coronavirus; infection; virus; protein; cells; disease; study; cell; syndrome; treatment; studies; transmission; receptor; data; cases; analysis; vaccine; host; spike; antibodies; antibody; results; proteins; response; samples; viruses; time; symptoms; risk; coronaviruses; replication; pneumonia; pandemic; infections; lung; days; activity; detection; drug; entry; expression; case; outbreak; development; drugs; vaccines; system; genome; responses verbs: used; shown; including; based; reported; binding; associated; infected; identified; caused; suggests; found; increases; developing; detected; provides; compared; induce; followed; testing; confirmed; inhibit; indicating; reduce; performed; neutralizing; required; observed; targets; related; treating; considering; leading; reveal; contain; known; emerged; demonstrated; describe; determine; resulting; expressed; involving; mediated; made; obtain; prevent; occurs; remained; needs adjectives: viral; respiratory; human; severe; clinical; acute; covid-19; immune; novel; high; positive; potential; different; specific; antiviral; anti; new; inflammatory; first; several; available; higher; non; important; therapeutic; negative; like; possible; molecular; similar; infected; structural; early; low; many; recent; effective; pro; significant; asymptomatic; infectious; multiple; current; single; common; lower; small; rapid; large; key adverbs: also; however; well; therefore; highly; currently; respectively; recently; previously; even; still; significantly; moreover; furthermore; especially; mainly; potentially; rapidly; less; directly; first; critically; now; additionally; clinically; particularly; yet; already; interestingly; together; approximately; far; relatively; worldwide; prior; finally; specifically; hence; often; closely; subsequently; likely; later; similarly; much; rather; fully; indeed; widely; effectively pronouns: we; it; its; their; our; they; i; them; his; he; us; she; itself; her; you; one; your; themselves; my; him; nsp10; ourselves; rad5; mg; himself; ours; nsp15; me; ⍬; nsp7; mrnas; theirs; il-6r; covid-19; 's; −; βcovs; ys110; yours; yis26g81; ybs20; y.org/protp; wuhan-12; turns; the~5-fold; theaflavin; sdpp4; s230; s; pubchem proper nouns: SARS; CoV-2; CoV; COVID-19; MERS; ACE2; RNA; S; China; Coronavirus; PCR; Fig; Wuhan; RT; East; Middle; RBD; M; T; Health; Table; CoVs; Disease; IgG; C; S1; IFN; TMPRSS2; Syndrome; Respiratory; 3CL; Novel; S2; IgM; N; CT; IL-6; COV-2; Vero; II; J; CoV-1; ELISA; March; Human; USA; United; ARDS; sera; sha keywords: sars; cov-2; covid-19; cov; ace2; mers; patient; rna; china; coronavirus; cell; protein; pcr; infection; virus; vaccine; east; rbd; human; wuhan; clinical; severe; ifn; 3cl; middle; drug; disease; respiratory; antibody; transmission; pro; olfactory; cns; vero; usa; tmprss2; study; site; mpro; il-6; flavonoid; elisa; dna; day; compound; cancer; bangladesh; animal; air; ace-2 one topic; one dimension: cov file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189397/ titles(s): Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) three topics; one dimension: sars; sars; cov file(s): https://doi.org/10.1101/2020.10.26.356014, https://doi.org/10.1128/cmr.00184-20, https://www.ncbi.nlm.nih.gov/pubmed/26055715/ titles(s): COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms | SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles | Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS five topics; three dimensions: sars cov protein; cov sars coronavirus; covid patients sars; sars cov covid; cov mers sars file(s): https://www.ncbi.nlm.nih.gov/pubmed/33098476/, https://doi.org/10.1101/2020.09.22.308023, https://doi.org/10.1002/path.5471, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520657/, https://doi.org/10.1101/2020.06.20.159715 titles(s): An Overview of the Crystallized Structures of the SARS-CoV-2 | Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain | Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) | A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts | Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 Type: cord title: keyword-cov-cord date: 2021-05-24 time: 22:48 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:cov ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-298989-qk0k2lmz author: , Umesh title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target date: 2020-05-13 words: 3226.0 sentences: 179.0 pages: flesch: 52.0 cache: ./cache/cord-298989-qk0k2lmz.txt txt: ./txt/cord-298989-qk0k2lmz.txt summary: title: Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target Carnosol exhibited highest binding affinity -8.2 Kcal/mol and strong and stable interactions with the amino acid residues present on the active site of SARS-CoV-2 Mpro. Our virtual screening results suggest that these small chemical molecules can be used as potential inhibitors against SARS-CoV-2 Mpro and may have an anti-viral effect on nCoV. SARS-CoV-2 main protease, a potential drug target, crystal structure (PDB-ID: 6Y84) was available and used for docking simulation and identification of potential drug molecule form Indian spices. Details of various kinds of interaction shown between the amino acids near the active site of SARS-CoV-2 main protease along with their respective inhibitor constant (Ki) and biological source and binding energy. Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study abstract: The 2019-novel coronavirus (nCoV) has caused a global health crisis by causing coronavirus disease-19 (COVID-19) pandemic in the human population. The unavailability of specific vaccines and anti-viral drug for nCoV, science demands sincere efforts in the field of drug design and discovery for COVID-19. The novel coronavirus main protease (SARS-CoV-2 Mpro) play a crucial role during the disease propagation, and hence SARS-CoV-2 Mpro represents as a drug target for the drug discovery. Herein, we have applied bioinformatics approach for screening of chemical compounds from Indian spices as potent inhibitors of SARS-CoV-2 main protease (PDBID: 6Y84). The structure files of Indian spices chemical compounds were taken from PubChem database or Zinc database and screened by molecular docking, by using AutoDock-4.2, MGLTools-1.5.6, Raccoon virtual screening tools. Top 04 hits based on their highest binding affinity were analyzed. Carnosol exhibited highest binding affinity -8.2 Kcal/mol and strong and stable interactions with the amino acid residues present on the active site of SARS-CoV-2 Mpro. Arjunglucoside-I (-7.88 Kcal/mol) and Rosmanol (-7.99 Kcal/mol) also showed a strong and stable binding affinity with favourable ADME properties. These compounds on MD simulations for 50 ns shows strong hydrogen-bonding interactions with the protein active site and remains stable inside the active site. Our virtual screening results suggest that these small chemical molecules can be used as potential inhibitors against SARS-CoV-2 Mpro and may have an anti-viral effect on nCoV. However, further validation and investigation of these inhibitors against SARS-CoV-2 main protease are needed to claim their candidacy for clinical trials. Communicated by Ramaswamy H. Sarma url: https://www.ncbi.nlm.nih.gov/pubmed/32362243/ doi: 10.1080/07391102.2020.1763202 id: cord-319184-voc0eqb9 author: Abduljalil, Jameel M. title: Laboratory diagnosis of SARS-CoV-2: available approaches and limitations date: 2020-06-14 words: 1115.0 sentences: 101.0 pages: flesch: 44.0 cache: ./cache/cord-319184-voc0eqb9.txt txt: ./txt/cord-319184-voc0eqb9.txt summary: Clinical 397 evaluation of the cobas SARS-CoV-2 test and a diagnostic platform switch during 48 398 hours in the midst of the COVID-19 pandemic Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-406 19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro Rapid and visual detection of 2019 458 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal 459 amplification assay Transcription Loop-Mediated Isothermal Amplification Assays Targeting SARS-CoV-2 Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of 467 SARS-CoV-2 Development of a reverse 469 transcription-loop-mediated isothermal amplification as a rapid early-detection method for 470 novel SARS-CoV-2 Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Development and clinical application of a 500 rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis Novel Antigen-Based Rapid Detection Test for the Diagnosis of SARS-CoV-2 in Serological immunochromatographic 525 approach in diagnosis with SARS-CoV-2 infected COVID-19 patients abstract: Abstract The ongoing pandemic of SARS-CoV-2 is a one of the most devastating outbreaks witnessed in the last 100 years. The outbreak started in China's hinterland and spread rapidly to almost every country culminating in woefully overwhelmed healthcare systems in most countries. The only approved diagnostic test to accompany radiographic evaluation is the reverse-transcriptase PCR. However, the applicability of this test in diagnosis and surveillance is challenged by global shortage in reagents and unavailability of well-equipped laboratories with specialized staff in several low- and middle-income countries. The need for development of accurate and rapid diagnostic assays became apparent. Handful of immunodiagnostic tests and other molecular approaches were developed and tested. Other recently developed point-of-care molecular tests are expected to be helpful in pandemic management since no particular skills are required from the operator. Fortunately, handful of serological tests have granted authorization to be used under emergency situation by FDA in diagnosis of SARS-CoV-2. url: https://api.elsevier.com/content/article/pii/S2052297520300652 doi: 10.1016/j.nmni.2020.100713 id: cord-324856-hf969tav author: Abir, Tanvir title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys date: 2020-07-21 words: 4144.0 sentences: 221.0 pages: flesch: 53.0 cache: ./cache/cord-324856-hf969tav.txt txt: ./txt/cord-324856-hf969tav.txt summary: title: Factors Associated with the Perception of Risk and Knowledge of Contracting the SARS-Cov-2 among Adults in Bangladesh: Analysis of Online Surveys Since the sheer illness of the whole country is sufficient to destroy the health care system, this current study is to examine changes of individual perception of risk for contracting SARS-Cov-2, and the awareness level in Bangladesh during the early and late lockdowns implemented by the government of Bangladesh. In this study, males who were worried about contracting SARS-Cov-2 were more likely to perceive themselves as being at high risk of contracting the infection, as well as those who did not quarantine themselves or only did so at the request of the public health officers. Moreover, in India, it was found that a higher level of knowledge on COVID-19 was associated with the high-risk perception of contracting the infection during the consistent lockdown period [28] . abstract: This study investigated the perception and awareness of risk among adult participants in Bangladesh about Coronavirus Disease 2019 (COVID-19). During the lockdown era in Bangladesh at two different time points, from 26−31 March 2020 (early lockdown) and 11−16 May 2020 (late lockdown), two self-administered online surveys were conducted on 1005 respondents (322 and 683 participants, respectively) via social media. To examine risk perception and knowledge-related factors towards COVID-19, univariate and multiple linear regression models were employed. Scores of mean knowledge (8.4 vs. 8.1, p = 0.022) and perception of risk (11.2 vs. 10.6, p < 0.001) differed significantly between early and late lockdown. There was a significant decrease in perceived risk scores for contracting SARS-Cov-2 [β = −0.85, 95%CI: −1.31, −0.39], while knowledge about SARS-Cov-2 decreased insignificantly [β = −0.22, 95%CI: −0.46, 0.03] in late lockdown compared with early lockdown period. Self-quarantine was a common factor linked to increased perceived risks and knowledge of SARS-Cov-2 during the lockdown period. Any effort to increase public awareness and comprehension of SARS-Cov-2 in Bangladesh will then offer preference to males, who did not practice self-quarantine and are less worried about the propagation of this kind of virus. url: https://www.ncbi.nlm.nih.gov/pubmed/32708161/ doi: 10.3390/ijerph17145252 id: cord-297132-lhfa9fl5 author: Aghagoli, Ghazal title: Neurological Involvement in COVID-19 and Potential Mechanisms: A Review date: 2020-07-13 words: 5940.0 sentences: 280.0 pages: flesch: 36.0 cache: ./cache/cord-297132-lhfa9fl5.txt txt: ./txt/cord-297132-lhfa9fl5.txt summary: In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. The novel 2019 coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) results in a variety of symptoms including fever, cough, and fatigue [1] . The Kawasaki-like syndrome that is now described in young patients following COVID-19 infection and associated with a hyper-inflammatory state is further suggestive of a vascular inflammatory potential of SARS-CoV-2 [48, 49] . Once established in the CNS, SARS-CoV, the virus responsible for Severe Acute Respiratory Syndrome (SARS), has been shown to be capable of inducing rapid transneuronal spread and death of infected neurons in transgenic mice models expressing human ACE2 receptors [63] . abstract: As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury. url: https://www.ncbi.nlm.nih.gov/pubmed/32661794/ doi: 10.1007/s12028-020-01049-4 id: cord-343302-g9vcchrh author: Agrawal, Anurodh Shankar title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection date: 2016-08-19 words: 4795.0 sentences: 212.0 pages: flesch: 49.0 cache: ./cache/cord-343302-g9vcchrh.txt txt: ./txt/cord-343302-g9vcchrh.txt summary: title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Here, we further characterized this novel human mAb in our Tg mouse model of MERS-CoV infection and showed prophylactic and therapeutic protection of mice treated with m336 before and after a lethal challenge with the virus, respectively. In our studies, we noted that passively transferred with 1 mg and 0.1 mg of m336 monoclonal antibodies to individual mice 12 h prior to challenge with 1,000 LD 50 of MERS-CoV resulted in 100% and 75% protection against lethality, respectively (Fig. 1) , suggesting that using 0.1 mg m336/mouse as a prophylaxis is suboptimal to completely neutralize viral infection, thereby allowing residual viruses to replicate within lungs during the course of infection. abstract: Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection. url: https://doi.org/10.1038/srep31629 doi: 10.1038/srep31629 id: cord-272113-j82z4q8x author: Akaji, Kenichi title: Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease date: 2020-08-27 words: 6459.0 sentences: 281.0 pages: flesch: 45.0 cache: ./cache/cord-272113-j82z4q8x.txt txt: ./txt/cord-272113-j82z4q8x.txt summary: Instead of an exhaustive survey of the inhibitors [21] , we provide an overview of several typical inhibitors, and our recent efforts for the rational design of new scaffolds are discussed based on the inhibitory mechanism and structural interactions with SARS-CoV 3CL pro . Following the interaction with the active center of the SARS-CoV 3CL pro , the nucleophilic Cys145 thiolate generated by a proton-withdrawing effect caused by His41 at the catalytic dyad promotes a typical 1,4-addition to the α,β-unsaturated structure of the Michael acceptor ( Figure 3 ). These data also indicate that the corresponding S1 pocket of the SARS-CoV 3CL pro might accept a simple ring structure containing heteroatoms at this specific interaction site, which provides a clue to our design of a potent substrate-based inhibitor described later in this review. abstract: Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CL(pro)) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CL(pro) based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CL(pro) inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2. url: https://doi.org/10.3390/molecules25173920 doi: 10.3390/molecules25173920 id: cord-304617-5ozf18lg author: Al-Khafaji, Khattab title: Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2 date: 2020-05-15 words: 4367.0 sentences: 227.0 pages: flesch: 51.0 cache: ./cache/cord-304617-5ozf18lg.txt txt: ./txt/cord-304617-5ozf18lg.txt summary: The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The got protein-drug complex structures from covalent docking were submitted to MD simulations (saquinavir, ritonavir, and remdesivir with SARS-CoV-2 Mpro). The effect of drug-protein interactions upon dynamics of biological system is a fundamental in drug discovery thereby we used RMSD to investigate the influence of saquinavir, ritonavir, and remdesivir upon the stability of SARS-CoV-2 Mpro. One of the more noteworthy findings in this study is that MD simulation analysis that saquinavir, ritonavir, and remdesivir can form stable interaction inside the binding site of SARS-CoV-2 Mpro. abstract: SARS-CoV-2 is a new generation of coronavirus, which was first determined in Wuhan, China, in December 2019. So far, however, there no effective treatment has been found to stop this new generation of coronavirus but discovering of the crystal structure of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) may facilitate searching for new therapies for SARS-COV-2. The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. We conducted the covdock module MMGBSA module in the Schrodinger suite 2020-1, to examine the covalent bonding utilizing. Besides, we submitted the top three drugs to molecular dynamics simulations via Gromacs 2018.1. The covalent docking showed that saquinavir, ritonavir, remdesivir, delavirdine, cefuroxime axetil, oseltamivir and prevacid have the highest binding energies MMGBSA of –72.17, −72.02, −65.19, −57.65, −54.25, −51.8, and −51.14 kcal/mol, respectively. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The current study provides a powerful in silico results, means for rapid screening of drugs as anti-protease medications and recommend that the above-mentioned drugs can be used in the treatment of SARS-CoV-2 in combined or sole therapy. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1764392 doi: 10.1080/07391102.2020.1764392 id: cord-354398-f3cg8gi1 author: Al-Saud, Haya title: Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing date: 2020-09-20 words: 4018.0 sentences: 199.0 pages: flesch: 55.0 cache: ./cache/cord-354398-f3cg8gi1.txt txt: ./txt/cord-354398-f3cg8gi1.txt summary: The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. We validated the modified Invitrogen Forensic DNA Purification kit in extracting in-laboratory propagated SARS-COV-2 RNA by conducting manual and automated extractions on titrations from 15 000 copies to 60 copies of SARS-COV-2 followed by RT-qPCR methods: the commercially available TaqPath One-Step qRT-QP-CR kit (using the N, S, and ORF1b genes) and primers and probes from Metabion, Germany to establish an inhouse RT-qPCR assay based on E, RdRp2 and RdRp4 gene detection as per recommended SARS-COV-2 testing from CDC and WHO. abstract: BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has prompted a need for mass testing to identify patients with viral infection. The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. OBJECTIVES: Report on the use of a DNA extraction kit, after modifications, to extract viral RNA that could then be detected using an FDA-approved SARS-COV-2 RT-qPCR assay. MATERIALS AND METHODS: Initially, automated RNA extraction was performed using a modified DNA kit on samples from control subjects, a bacteriophage, and an RNA virus. We then verified the automated extraction using the modified kit to detect in-lab propagated SARSCOV-2 titrations using an FDA approved commercial kit (S, N, and ORF1b genes) and an in-house primer-probe based assay (E, RdRp2 and RdRp4 genes). RESULTS: Automated RNA extraction on serial dilutions SARS-COV-2 achieved successful one-step RT-qPCR detection down to 60 copies using the commercial kit assay and less than 30 copies using the in-house primer-probe assay. Moreover, RT-qPCR detection was successful after automated RNA extraction using this modified protocol on 12 patient samples of SARS-COV-2 collected by nasopharyngeal swabs and stored in viral transport media. CONCLUSIONS: We demonstrated the capacity of a modified DNA extraction kit for automated viral RNA extraction and detection using a platform that is suitable for mass testing. LIMITATIONS: Small patient sample size. CONFLICT OF INTEREST: None. url: https://doi.org/10.5144/0256-4947.2020.373 doi: 10.5144/0256-4947.2020.373 id: cord-324978-9qfhsj3n author: Alagaili, Abdulaziz N. title: Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia date: 2014-02-25 words: 3565.0 sentences: 165.0 pages: flesch: 53.0 cache: ./cache/cord-324978-9qfhsj3n.txt txt: ./txt/cord-324978-9qfhsj3n.txt summary: The presence of viral nucleic acids in rectal and nasal swabs and a subset of serum and whole blood samples was assayed by reverse transcriptionquantitative PCR (RT-qPCR) with primers targeting the upE and ORF1a genome regions of MERS-CoV (16, 17) . Rectal and nasal swabs collected in parallel with serum samples from the same animals were assayed for MERS-CoV nucleic acids by RT-qPCR. PCR analysis of a random selection of serum and whole blood samples collected from nasal or rectal swab PCR-positive, seropositive, and seronegative DC revealed no evidence of viremia (see Table S1 in the supplemental material). Definitive evidence that DC can be infected with MERS-CoV was obtained when viral sequences were detected in nasal swabs from DC sampled in close proximity to outbreaks of the disease among humans in Qatar (11) and Jeddah, KSA (10) . abstract: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats. url: https://doi.org/10.1128/mbio.00884-14 doi: 10.1128/mbio.00884-14 id: cord-337835-78i6j11i author: Alfaraj, Sarah H. title: The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus date: 2017-02-09 words: 1534.0 sentences: 115.0 pages: flesch: 62.0 cache: ./cache/cord-337835-78i6j11i.txt txt: ./txt/cord-337835-78i6j11i.txt summary: title: The impact of co-infection of influenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus 1 We present four cases of combined infection with influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A nasopharyngeal swab was positive for MERS-CoV with Ct value upE gene 37; ORF1A 36 and negative for Influenza. A repeat swab after 3 days was negative for MERS-CoV but positive for influenza A. The NLST worked with the FES teams in the North West (NW) and West Midlands (WMids) regions of England to audit the reporting of Legionella cases with onset dates during each calendar year between 2012 and 2014, inclusive. WHO guidelines for investigation of cases of human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0163445317300488 doi: 10.1016/j.jinf.2017.02.001 id: cord-305704-grzrkff9 author: Almutairi, Abdulelah title: Dermatological Manifestations in Patients With SARS-CoV-2: A Systematic Review date: 2020-07-28 words: 2289.0 sentences: 134.0 pages: flesch: 46.0 cache: ./cache/cord-305704-grzrkff9.txt txt: ./txt/cord-305704-grzrkff9.txt summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. The following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. The results were then filtered to include only original research studies examining the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. After searching the abstracts and reviewing the eligibility criteria in identified potential abstracts, a total of seven studies [14] [15] [16] [17] [18] [19] [20] were considered as eligible to be included in the present systematic review, covering a total of 555 patients with SARS-CoV-2 who had dermatological symptoms in the form of skin lesions. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. However, the identification and characteristics of these manifestations are still controversial. This review article aims to evaluate the medical literature and explore the dermatological clinical manifestations in patients with SARS-CoV-2. The literature was reviewed through MEDLINE®, Ovid, PubMed®, and Embase®. Searching terms included were a combination of "dermatological" OR "skin" AND "symptoms" OR "manifestations" AND "SARS-CoV-2". The following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. A total of 879 studies were retrieved. Following the exclusion of studies on animals and including only studies on humans, 32 studies emerged. Altogether, seven studies were identified as eligible, covering 555 patients with SARS-CoV-2 who had dermatological symptoms. Three studies were retrospective, two studies were prospective, and two studies were case series. Different types of dermatological lesions can occur in patients with SARS-CoV-2, most commonly erythema, urticaria, and varicella-like rash. Dermatological manifestations with SARS-CoV-2 can be misdiagnosed with other conditions. Further studies with robust design are needed. url: https://www.ncbi.nlm.nih.gov/pubmed/32775112/ doi: 10.7759/cureus.9446 id: cord-321851-ku4z34lu author: Alosaimi, Bandar title: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract date: 2020-02-29 words: 5619.0 sentences: 299.0 pages: flesch: 45.0 cache: ./cache/cord-321851-ku4z34lu.txt txt: ./txt/cord-321851-ku4z34lu.txt summary: Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. The lower respiratory tract samples from MERS-CoV infected patients and healthy non-infected controls were used to quantify expression levels of the main 12 human pro-inflammatory cytokines and chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, and GM-CSF). A side-by-side analysis of the data derived from the RT 2 -PCR profiling of pulmonary Th1/Th2 responses showed that genes encoding Th1 and Th2-related cytokines and chemokines were largely downregulated in the lower respiratory tract of MERS-CoV infected patients. Therefore, the high expression of inflammatory cytokines and downregulation of the Th1 and Th2 immune responses in the lower respiratory tracts of MERS-CoV infected patients may contribute to a more severe infection, higher case fatality, lung inflammation, and immunopathology. abstract: Abstract MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies. url: https://doi.org/10.1016/j.cyto.2019.154895 doi: 10.1016/j.cyto.2019.154895 id: cord-321855-7b1c2xdh author: Alshami, Alanoud title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia date: 2020-10-30 words: 3380.0 sentences: 190.0 pages: flesch: 56.0 cache: ./cache/cord-321855-7b1c2xdh.txt txt: ./txt/cord-321855-7b1c2xdh.txt summary: title: Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. have examined 24 asymptomatic infected individuals with a history of close contact with SARS-COV-2 confirmed cases and found that only 20% of them developed symptoms. Our findings are in light with a recent study that reported a 59% prevalence of loss of taste and smell in a cohort of COVID-19 patients [15] . Sudden onset of loss of smell and taste were prevalent in our study and were key symptoms of mild disease. abstract: OBJECTIVES: In this study, we aimed to study the clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals. DESIGN: Cross-sectional study. SETTING: Governmental- designated facility in the eastern province, Saudi Arabia. PARTICIPANTS: 128 laboratory-confirmed COVID-19 quarantined individuals who had a history of travel abroad in the last 14 days before the quarantine or were in direct contact with laboratory-confirmed cases. The study was from March 18th-till April 16th. PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. RESULTS: Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI, 12.4–21.6) from the first positive PCR vs. 11days (95% CI, 8.7–13.3) in the asymptomatic group (P = 0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%. CONCLUSION: The prevalence of asymptomatic carriers among quarantined travelers and those identified by contact tracing is high in our study. Therefore, testing, tracing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell were the most common presentations in our mild symptomatic residents and should be used as a screening tool for COVID-19. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control. url: https://doi.org/10.1371/journal.pone.0241258 doi: 10.1371/journal.pone.0241258 id: cord-294912-xl0wzi16 author: Alteri, Claudia title: Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients date: 2020-09-08 words: 3630.0 sentences: 216.0 pages: flesch: 49.0 cache: ./cache/cord-294912-xl0wzi16.txt txt: ./txt/cord-294912-xl0wzi16.txt summary: Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients. In this study, the presence of SARS-CoV-2 genome was evaluated in 55 SARS-CoV-2 rtPCR negative nasopharyngeal swabs from COVID-19 suspected patients thanks to a quantitative ad hoc designed assay based on ddPCR. This proof-of-concept study shows that an in-house ddPCR-based assay can allow an efficient detection of SARS-CoV-2 at low copy number in symptomatic cases resulted negative by standard rtPCR. abstract: Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32898153/ doi: 10.1371/journal.pone.0236311 id: cord-283956-zgrtux7i author: Amin, Sk. Abdul title: Fight against novel coronavirus: A perspective of medicinal chemists date: 2020-06-12 words: 5095.0 sentences: 356.0 pages: flesch: 52.0 cache: ./cache/cord-283956-zgrtux7i.txt txt: ./txt/cord-283956-zgrtux7i.txt summary: Like other RNA viruses, the functional significance of this Mpro or chymotrypsin-like protease (3CLpro) of SARS-CoV-2 emerges as an attractive drug target for the development of anti-viral agents. A group of scientists from the Cairo University, Egypt predicted COVID-19 spike binding site to a cell-surface receptor namely Glucose Regulated Protein 78 (GRP78) by employing structural bioinformatics in combination with protein-protein docking [55] . An early virtual screening (VS) study of FDA approved drugs (retrieved from Selleckchem Inc.) against the first resolved SARS-CoV-2 Mpro crystal structure (PDB: 6LU7) was performed. In another study, Elfiky [67] reported SARS-CoV-2 RdRp targeted molecular docking study of some anti-polymerase drugs which have been approved for use against various viruses. This study deals with the information currently available on potential targets for therapeutic invention and screening of new compounds or drug repurposing against SARS-CoV-2 (Figure 8 ). Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 abstract: The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents. url: https://www.ncbi.nlm.nih.gov/pubmed/32563814/ doi: 10.1016/j.ejmech.2020.112559 id: cord-272010-kc0gi3cj author: Anand, Sai Priya title: Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date: 2020-09-29 words: 3661.0 sentences: 216.0 pages: flesch: 56.0 cache: ./cache/cord-272010-kc0gi3cj.txt txt: ./txt/cord-272010-kc0gi3cj.txt summary: The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 abstract: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction. url: https://doi.org/10.3390/v12101104 doi: 10.3390/v12101104 id: cord-310239-mmvuij3k author: Arentz, Susan title: Clinical significance summary: Preliminary results of a rapid review of zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections date: 2020-08-01 words: 3941.0 sentences: 215.0 pages: flesch: 47.0 cache: ./cache/cord-310239-mmvuij3k.txt txt: ./txt/cord-310239-mmvuij3k.txt summary: Indirect evidence from systematic reviews have found zinc supplementation is effective for the prevention of acute respiratory infections in young children and zinc lozenges may reduce the duration of the common cold in adults. As of the 9 June 2020, the preliminary findings of a rapid review of zinc for the prevention or treatment Pending any definitive evidence, clinicians might consider assessing the zinc status of people with chronic disease co-morbidities and older adults as part of a SARS-CoV-2 clinical work-up, as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2. The primary objective of this rapid review was to assess the effects of zinc on the incidence, duration and severity of acute upper or lower respiratory tract infections caused by SARS-CoV-2 infection in people of any age and of any zinc status when used as a preventive supplement or as a therapy. abstract: nan url: https://doi.org/10.1016/j.aimed.2020.07.009 doi: 10.1016/j.aimed.2020.07.009 id: cord-347734-0z2kin6r author: Armann, J. P. title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates date: 2020-07-17 words: 2294.0 sentences: 138.0 pages: flesch: 51.0 cache: ./cache/cord-347734-0z2kin6r.txt txt: ./txt/cord-347734-0z2kin6r.txt summary: title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates However, there is reason to believe that children play a less significant role in SARS-CoV-2 transmission compared to influenza, making control measures focused on this age group less effective: Most countries-including Germany-report a much lower proportion of cases in children compared to their population size 4-6 . The findings from this unique study in older students and their teachers indicate that the prevalence of IgG antibodies against SARS-CoV-2 remains extremely low after the first wave of the corona pandemic in Germany. In fact, 5 of the 12 participants with antibodies against SARS-CoV-2 had a personal or household history of COVID-19, yielding a ratio of unidentified to identified cases of 2.4, which is much smaller than that previously assumed by some authors 9 . abstract: Background: School closures are part of the SARS-CoV-2 pandemic control measures in many countries, based on the assumption that children play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza. We therefore performed a SARS-CoV-2 seropraevalence-study in students and teachers to assess their role in the SARS-CoV-2 transmission. Methods: Students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests. Findings: 1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays we could exclude 16 participants with a positive or equivocal results after initial testing. Interpretation: Students and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group, making school closures not appear appropriate as a strategy in this low prevalence settings. Funding: This study was supported by a grant from the state of Saxony url: https://doi.org/10.1101/2020.07.16.20155143 doi: 10.1101/2020.07.16.20155143 id: cord-271648-m2c5bvuj author: Ashour, Hossam M. title: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks date: 2020-03-04 words: 7536.0 sentences: 401.0 pages: flesch: 56.0 cache: ./cache/cord-271648-m2c5bvuj.txt txt: ./txt/cord-271648-m2c5bvuj.txt summary: Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. However, unlike SARS-CoV, human-to-human transmission of MERS-CoV is not easy and has not been confirmed except in cases of very close contact with infected patients in health care settings [67] . Similar to the adaptation of SARS-CoV to human host, MERSr-CoVs that are circulating in bats had to undergo several amino acid changes in RBD of S protein to become capable of infecting camels and humans ( Figure 2 ) [74] . S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model abstract: Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat. url: https://doi.org/10.3390/pathogens9030186 doi: 10.3390/pathogens9030186 id: cord-255883-mz6nyisw author: Asif, Muhammad title: COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties date: 2020-08-14 words: 5273.0 sentences: 283.0 pages: flesch: 44.0 cache: ./cache/cord-255883-mz6nyisw.txt txt: ./txt/cord-255883-mz6nyisw.txt summary: Essential oils (EOs) have long been known to have anti-inflammatory, immunomodulatory, bronchodilatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2 virus. An in vitro study conducted by Hoffmann and colleagues revealed that SARC-CoV-2 depends on cellular serine protease (TMPRSS2) for S proteins priming which are known to interact with human ACE2 receptors in the lungs and facilitate entry into the cells. The authors opted the following keywords to find relevant studies: "essential oils", "antiviral", "COVID-19", "SARC-CoV-2", "bronchodilation", "immunomodulatory'''', "anti-inflammatory'''', "corona virus''''. Thus, on the basis of these docking and in vitro studies, it is proposed that garlic essential oils and their isolated constituents, especially DAS, have potential to prevent the entry of virus into host cells as well as to activate molecular antioxidant pathways that decrease the secretions of culprit pro-inflammatory cytokines. Essential oils have long been known to have anti-inflammatory, antioxidant, immunomodulatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2. abstract: Coronavirus disease of 2019 (COVID-19) has emerged as a global health threat. Unfortunately, there are very limited approved drugs available with established efficacy against the SARs-CoV-2 virus and its inflammatory complications. Vaccine development is actively being researched, but it may take over a year to become available to general public. Certain medications, for example, dexamethasone, antimalarials (chloroquine/hydroxychloroquine), antiviral (remdesivir), and IL-6 receptor blocking monoclonal antibodies (tocilizumab), are used in various combinations as off-label medications to treat COVID-19. Essential oils (EOs) have long been known to have anti-inflammatory, immunomodulatory, bronchodilatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2 virus. Owing to their lipophilic nature, EOs are advocated to penetrate viral membranes easily leading to membrane disruption. Moreover, EOs contain multiple active phytochemicals that can act synergistically on multiple stages of viral replication and also induce positive effects on host respiratory system including bronchodilation and mucus lysis. At present, only computer-aided docking and few in vitro studies are available which show anti-SARC-CoV-2 activities of EOs. In this review, role of EOs in the prevention and treatment of COVID-19 is discussed. A discussion on possible side effects associated with EOs as well as anti-corona virus claims made by EOs manufacturers are also highlighted. Based on the current knowledge a chemo-herbal (EOs) combination of the drugs could be a more feasible and effective approach to combat this viral pandemic. [Image: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/32803479/ doi: 10.1007/s10787-020-00744-0 id: cord-268468-036i1082 author: Asif, Muhammad title: The role of biosensors in COVID-19 outbreak date: 2020-09-18 words: 3204.0 sentences: 189.0 pages: flesch: 43.0 cache: ./cache/cord-268468-036i1082.txt txt: ./txt/cord-268468-036i1082.txt summary: In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor and surface plasmon resonance biosensors in the detection of SARS-CoV-2 has been underscored. In this outbreak, three different types of diagnosis tests are being used including (i) chest CT scan along with clinical indications, (ii) RNA detection using RT-PCR assay and (iii) lateral flow assays, full automatic chemiluminescence method, enzyme-linked immunosorbent assay (ELISA) for the determination of antibodies [5] . In this review, we have summarized the biosensor based technologies which are able to detect SARS-CoV-2 effectively. The peptide monolayer was successfully coated on SPR biosensor and further functionalized with virus nucleocapsid protein which was finally able to detect SARS-CoV-2 antibodies at nanomolar level. The sensing aptitude of the biosensor was evaluated employing antigen protein, self-cultured virus, and nasopharyngeal swab samples taken from people infected with COVID-19 pneumonia. abstract: Herein, we have summarized and argued about biomarkers and indicators used for the detection of SARS-CoV-2. Antibody detection methods are not considered suitable to screen individuals at early stages and asymptomatic cases. The diagnosis of COVID-19 using biomarkers and indicators at point of care level is much crucial. Therefore, it is urgently needed to develop rapid and sensitive detection methods which can target antigens. We have critically elaborated key role of biosensors to cope the outbreak situation. In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor and surface plasmon resonance biosensors in the detection of SARS-CoV-2 has been underscored. Finally, we have outlined pros and cons of diagnostic approaches as-well-as future directions. url: https://www.ncbi.nlm.nih.gov/pubmed/32984642/ doi: 10.1016/j.coelec.2020.08.011 id: cord-256508-ce59ovan author: Asselah, Tarik title: COVID-19: discovery, diagnostics and drug development date: 2020-10-08 words: 9214.0 sentences: 556.0 pages: flesch: 46.0 cache: ./cache/cord-256508-ce59ovan.txt txt: ./txt/cord-256508-ce59ovan.txt summary: To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The current diagnostic strategy to identify patients with COVID-19 is to test samples taken from the respiratory tract to assess for the presence of SARS-CoV-2 specific nucleic acid targets [47] . The neutralization assay is a laboratory-based test that uses live virus and cell culture methods to determine if patient antibodies can prevent viral infection in vitro [72] . A randomized, controlled, openlabel trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection and severe respiratory illness COVID-19 was performed [126] . Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals abstract: An epidemic of acute respiratory syndrome (Covid-19) started in humans in Wuhan in 2019, and became a pandemic. Groups from China Identified and sequenced the virus responsible for COVID-19, named SARS-CoV-2, and determined that it was a novel coronavirus (CoV) that shared high sequence identity with bat- and pangolin-derived SARS-like CoVs, suggesting a zoonotic origin. SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has allowed the development of diagnostic tools (e.g., RT-PCR). Additionally, serological tests can allow identification of persons who have been infected. In humans, CoVs tend to cause mild to moderate upper respiratory tract infections. The fatality rate is around 1-3% for infected persons. An acute respiratory distress syndrome (ARDS) likely due to an uncontrolled immune activation (“cytokine storm”) occurs in patients with severe disease and poor prognosis. Risk factors for mortality include: advanced age, obesity, diabetes, hypertension and other comorbidities. Drug repurposing has been used to rapidly identify potential treatment for COVID-19, which could move quickly to phase-3. Better knowledge of the virus, its enzymes, will be mandatory to develop more potent and specific direct-acting antiviral agents (DAA). In the long term, a vaccine to prevent infection would be crucial; however even if successful it might not be available before 2021-22. To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, the diagnostic tools, and the ongoing drug discovery effort. url: https://www.sciencedirect.com/science/article/pii/S0168827820336758?v=s5 doi: 10.1016/j.jhep.2020.09.031 id: cord-268034-7id7sfsu author: Auerswald, Heidi title: Assessment of Inactivation Procedures for SARS-CoV-2 date: 2020-05-28 words: 1620.0 sentences: 100.0 pages: flesch: 47.0 cache: ./cache/cord-268034-7id7sfsu.txt txt: ./txt/cord-268034-7id7sfsu.txt summary: This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. The buffers used in this lysis step yield varying results [11, 13, 15, 16] ; however, unlike 224 previous studies [11] , this study found that AVL buffer alone was successfully able to fully 225 inactivate up to 5 log10 of virus from three different primary isolates of SARS-CoV-2. Previous 234 studies have shown that GITC-lysis buffers are able to inactivate SARS-CoV-2 samples [11, 12] ; 235 however, the addition of Triton-X may be necessary for complete inactivation [11] . Therefore, formaldehyde treatment does not appear to be a 247 solution for increased molecular SARS-CoV-2 testing; however, it does remain a viable alternative 248 for sample inactivation or disinfection. abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety and biosecurity measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety and biosecurity for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability worldwide. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodian COVID-19 patients. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. url: https://doi.org/10.1101/2020.05.28.120444 doi: 10.1101/2020.05.28.120444 id: cord-342569-ja96xfns author: Azer, Samy A. title: COVID-19: Pathophysiology, diagnosis, complications and Investigational therapeutics date: 2020-08-05 words: 2669.0 sentences: 186.0 pages: flesch: 46.0 cache: ./cache/cord-342569-ja96xfns.txt txt: ./txt/cord-342569-ja96xfns.txt summary: On 31 December 2019, the Chinese authorities reported to the World Health Organisation (WHO) an emerging of a novice coronavirus, currently the virus is known as SARS-CoV-2 and the disease name is coronavirus-19 disease (COVID19) , that has emerged in patients from Wuhan city, Hubel Province [1] . Recently it was debated that targeting the Notch signalling to prevent SARS-CoV-2 infection and interfering with the progression of COVID-19associated heart and lungs disease pathogenesis [13] . It is not clear whether the observed SARS-CoV-2-associated liver injury is cause by direct viral injury or related to hepatoxic drugs, coexisting systemic inflammatory changes, sepsis, respiratory distress syndrome-induced hypoxia, and multiple organ failure [18] . In patients with type 2 diabetes mellitus who are infected with COVID-19, it is important to remember that two receptor proteins ACE-2 and dipeptidyl peptidase-4 (DPP-4) are test can detect IgM, and IgG antibodies against SARS-CoV-2 in the serum, plasma, and whole blood [23] . abstract: Abstract The novel coronavirus (COVID-19) outbreak started early in December 2019 in the Hubei province and its capital Wuhan of the People’s Republic of China and caused a global pandemic. The number of patients confined to this disease has exceeded nine million in more than 215 countries, and the number who died is over 480,600 (up to 25 June 2020). Coronaviruses were identified in the 1960s and recently identified to cause the Middle East Respiratory Syndrome (MERS-CoV) in 2012 and severe acute respiratory syndrome (SARS) in 2003. The current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the most recently identified. Patients with COVID-19 may be asymptomatic. Typical symptoms including fever, dry cough, and shortness of breath. Gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhea, have been reported—neurologically related symptoms, particularly anosmia, hyposmia, and dysgeusia, have also been reported. Physical examination may reveal a fever in over 44% of patients (and could be documented in over 88% of patients after admission), increased respiratory rate, acute respiratory disease, and maybe decreased consciousness, agitation, and confusion. This article aims at presenting an up-to-date review on the pathogenesis, diagnosis and complications of COVID-19 infection. Currently, no therapeutics have been found to be effective. Investigational therapeutics are briefly discussed. url: https://api.elsevier.com/content/article/pii/S2052297520300901 doi: 10.1016/j.nmni.2020.100738 id: cord-355567-60sfv60p author: Azuma, Kenichi title: Environmental factors involved in SARS-CoV-2 transmission: effect and role of indoor environmental quality in the strategy for COVID-19 infection control date: 2020-11-03 words: 9229.0 sentences: 436.0 pages: flesch: 42.0 cache: ./cache/cord-355567-60sfv60p.txt txt: ./txt/cord-355567-60sfv60p.txt summary: Recently, 36 researchers insisted on the potential risk of indoor airborne transmission of SARS-CoV-2 and the importance of sufficient and effective ventilation, particle filtration, and air sterilization as infection control measures inside buildings [43] . Therefore, the MHLW published a document titled "Prevention of the COVID-19 Clusters" Abbreviation: SARS-CoV severe acute respiratory syndrome coronavirus Fig. 1 Traditional Japanese office building HVAC systems: a a centralized HVAC system; and b a centralized ventilation system with an individual air-conditioning system on March 1, 2020 [94] , showing the need for adequate ventilation in buildings because a ventilation standard for infection control has not been established in general buildings in Japan and the characteristics of indoor spaces where the clusters occurred might include poor ventilation and crowding. abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new zoonotic agent that emerged in December 2019, causes coronavirus disease 2019 (COVID-19). This infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. SARS-CoV-2 spreads primarily via respiratory droplets during close person-to-person contact in a closed space, especially a building. This article summarizes the environmental factors involved in SARS-CoV-2 transmission, including a strategy to prevent SARS-CoV-2 transmission in a building environment. SARS-CoV-2 can persist on surfaces of fomites for at least 3 days depending on the conditions. If SARS-CoV-2 is aerosolized intentionally, it is stable for at least several hours. SARS-CoV-2 is inactivated rapidly on surfaces with sunlight. Close-contact aerosol transmission through smaller aerosolized particles is likely to be combined with respiratory droplets and contact transmission in a confined, crowded, and poorly ventilated indoor environment, as suggested by some cluster cases. Although evidence of the effect of aerosol transmission is limited and uncertainty remains, adequate preventive measures to control indoor environmental quality are required, based on a precautionary approach, because COVID-19 has caused serious global damages to public health, community, and the social economy. The expert panel for COVID-19 in Japan has focused on the “3 Cs,” namely, “closed spaces with poor ventilation,” “crowded spaces with many people,” and “close contact.” In addition, the Ministry of Health, Labour and Welfare of Japan has been recommending adequate ventilation in all closed spaces in accordance with the existing standards of the Law for Maintenance of Sanitation in Buildings as one of the initial political actions to prevent the spread of COVID-19. However, specific standards for indoor environmental quality control have not been recommended and many scientific uncertainties remain regarding the infection dynamics and mode of SARS-CoV-2 transmission in closed indoor spaces. Further research and evaluation are required regarding the effect and role of indoor environmental quality control, especially ventilation. url: https://doi.org/10.1186/s12199-020-00904-2 doi: 10.1186/s12199-020-00904-2 id: cord-030934-t7akdu6x author: Bahrami, Afsane title: Genetic and pathogenic characterization of SARS-CoV-2: a review date: 2020-08-26 words: 6472.0 sentences: 356.0 pages: flesch: 45.0 cache: ./cache/cord-030934-t7akdu6x.txt txt: ./txt/cord-030934-t7akdu6x.txt summary: The first case of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019. Bioinformatics analysis of the viral genome from one COVID-19 patient shared 89 and 82% sequence similarity with bat SARS-like-CoVZXC21 and human SARS-CoV, respectively [41] . In a recent report it was shown that SARS-CoV-2''s S-protein entry into 293/human ACE2 receptor cells is primarily mediated via endocytosis, and that PIKfyve, a TPC2 and cathepsin L are crucial for virus entry. Findings of an open-label nonrandomized clinical trial among 22 infected patients indicated that hydroxychloroquine treatment significantly reduced viral load in COVID-19 cases and its effectiveness is promoted by azithromycin [99] . The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response abstract: The first case of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in December 2019. This virus belongs to the beta-coronavirus group that contains a single stranded RNA with a nucleoprotein within a capsid. SARS-CoV-2 shares 80% nucleotide identity to SARS-CoV. The virus is disseminated by its binding to the ACE2 receptors on bronchial epithelial cells. The diagnosis of COVID-19 is based on a laboratory-based reverse transcription polymerase chain reaction (RT-PCR) test together with chest computed tomography imaging. To date, no antiviral therapy has been approved, and many aspects of the COVID-19 are unknown. In this review, we will focus on the recent information on genetics and pathogenesis of COVID-19 as well as its clinical presentation and potential treatments. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451412/ doi: 10.2217/fvl-2020-0129 id: cord-322811-6lebh7ca author: Baig, Mirza S. title: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells date: 2020-06-26 words: 4119.0 sentences: 245.0 pages: flesch: 53.0 cache: ./cache/cord-322811-6lebh7ca.txt txt: ./txt/cord-322811-6lebh7ca.txt summary: METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. Currently, the computational analysis of structural differences in human ACE2 impact its binding to the SARS-CoV-2 spike protein, which thereby lays a foundation for the design and development of ACE2-based peptide inhibitors of SARS-CoV-2 [47] [48] [49] . After a detailed analysis of interface residues, a small stretch of the ACE2 PD N-terminal region (23-amino acids: Glu23 to Leu45) was found to be interacting majorly with the SARS-CoV-2 spike protein ( Fig. 2 and Table 1 ). Computational alanine (A) scanning was performed to identify the critically important amino acids of the 23aa peptide inhibitor involved in binding to the SARS-CoV-2 spike protein. abstract: BACKGROUND AND OBJECTIVE: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. Hence, inhibition of this interaction could be a promising strategy to combat the SARS-CoV-2 infection. METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. CONCLUSION: Our findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40268-020-00312-5) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s40268-020-00312-5 doi: 10.1007/s40268-020-00312-5 id: cord-270550-if748w2n author: Bailey, Adam L. title: SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date: 2020-11-05 words: 5808.0 sentences: 440.0 pages: flesch: 49.0 cache: ./cache/cord-270550-if748w2n.txt txt: ./txt/cord-270550-if748w2n.txt summary: To ascertain whether human pluripotent stem cell-derived cardiomyocytes (hPSC-derived 150 CMs) can serve as an appropriate model to study cardiac SARS-CoV-2 infection, we measured 151 ACE2 mRNA expression in hPSC-derived CMs. Quantitative RT-PCR revealed that hPSC-152 derived CMs abundantly expressed ACE2 mRNA. We identified numerous host genes that were differentially 226 regulated upon SARS-CoV-2 infection in each of the examined cell types and two-dimensional 227 tissues (Fig. 3c) . 236 GO pathway analysis revealed that infected hPSC-derived CMs and two-dimensional co-237 culture tissues showed upregulation of genes associated with immune cell activation, stress-238 induced transcription, and responses to pathogens including viruses. Consistent with the 343 possibility that disrupted sarcomere gene expression might contribute to reduced EHT 344 contractility, immunostaining of hPSC-derived CMs infected with SARS-CoV-2 revealed evidence 345 of sarcomere loss 3 days following infection (Fig. 6c) , a time point that preceded cell death. abstract: Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19. url: https://doi.org/10.1101/2020.11.04.364315 doi: 10.1101/2020.11.04.364315 id: cord-257958-yehnlabq author: Barh, Debmalya title: Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19 date: 2020-10-10 words: 5431.0 sentences: 364.0 pages: flesch: 43.0 cache: ./cache/cord-257958-yehnlabq.txt txt: ./txt/cord-257958-yehnlabq.txt summary: In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. In this paper, we have used an integrative omics approach considering the SARS-CoV-2 infected host interactome, proteome, transcriptome, and bibliome datasets and analysed the COVID-19 associated host genetic information to identify common host pathways that are deregulated during SARS-CoV-2 infection and potential drugs targeting those pathways. In our analysis, we observed SARS-CoV-2 infection shares other viral pathways such as To identify pathway specific drugs, we used the genes involved in the five most important common pathways (viral processes including all the individual virus pathways, mRNA splicing, ubiquitin mediated proteolysis, cytokine signaling in immune system, and protein processing in endoplasmic reticulum). abstract: SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management. url: https://www.sciencedirect.com/science/article/pii/S0010482520303826?v=s5 doi: 10.1016/j.compbiomed.2020.104051 id: cord-328996-3sf2i45r author: Barthélémy, Romain title: Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome date: 2020-06-06 words: 1161.0 sentences: 100.0 pages: flesch: 59.0 cache: ./cache/cord-328996-3sf2i45r.txt txt: ./txt/cord-328996-3sf2i45r.txt summary: title: Efficacy of Almitrine in The Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome This monocenter retrospective study aimed to evaluate the association between almitrine 19 introduction and improvement of oxygenation in Sars-Cov-2 ARDS. Inclusion criteria in the study were: admission for respiratory failure, a diagnosis of ARDS 24 according to Berlin criteria 8 , laboratory confirmed Sars-Cov-2 infection, almitrine infusion in 25 ICU. In our 73 observational study, almitrine was associated with an increase in PaO 2 /FiO 2 ratio after 74 treatment. Furthermore, despite an associated improvement in PaO 2 /FiO 2 ratio, the majority 76 of patients receiving almitrine went on to needing additional rescue interventions or died. 77 This may be explained by the fact that, in our study, almitrine has been used as a rescue 78 therapy in severe patients with worsening hypoxemia and very low PaO 2 /FiO 2 ratio. abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0012369220316433?v=s5 doi: 10.1016/j.chest.2020.05.573 id: cord-274399-cd7cmpoj author: Barzin, Amir title: SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures date: 2020-09-29 words: 3304.0 sentences: 189.0 pages: flesch: 47.0 cache: ./cache/cord-274399-cd7cmpoj.txt txt: ./txt/cord-274399-cd7cmpoj.txt summary: This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This study identifies a very limited seroprevalence of SARS-CoV-2 among asymptomatic individuals accessing the UNC Health system. This study employed an EUA assay performed in a CLIA-certified laboratory on a venous blood sample, with demonstrated specificity to detect antibodies only to SARS-CoV-2, not to seasonal coronaviruses. Upon arrival for SARS-CoV-2 Seroprevalence in North Carolina ® routine care or scheduled visits for enrollment into the study, patients performed a consent procedure that included reviewing recent COVID-19 clinical history using UNC IRB-approved questionnaires. abstract: Characterizing the asymptomatic spread of SARS-CoV-2 is important for understanding the COVID-19 pandemic. This study was aimed at determining asymptomatic spread of SARS-CoV-2 in a suburban, Southern U.S. population during a period of state restrictions and physical distancing mandates. This is one of the first published seroprevalence studies from North Carolina and included multicenter, primary care, and emergency care facilities serving a low-density, suburban and rural population since description of the North Carolina state index case introducing the SARS-CoV-2 respiratory pathogen to this population. To estimate point seroprevalence of SARS-CoV-2 among asymptomatic individuals over time, two cohort studies were examined. The first cohort study, named ScreenNC, was comprised of outpatient clinics, and the second cohort study, named ScreenNC2, was comprised of inpatients unrelated to COVID-19. Asymptomatic infection by SARS-CoV-2 (with no clinical symptoms) was examined using an Emergency Use Authorization (EUA)-approved antibody test (Abbott) for the presence of SARS-CoV-2 IgG. This assay as performed under CLIA had a reported specificity/sensitivity of 100%/99.6%. ScreenNC identified 24 out of 2,973 (0.8%) positive individuals among asymptomatic participants accessing health care during 28 April to 19 June 2020, which was increasing over time. A separate cohort, ScreenNC2, sampled from 3 March to 4 June 2020, identified 10 out of 1,449 (0.7%) positive participants. url: https://doi.org/10.1128/mbio.02426-20 doi: 10.1128/mbio.02426-20 id: cord-331856-j0gedx43 author: Basile, K. title: Accuracy amidst ambiguity: false positive SARS-CoV-2 nucleic acid tests when COVID-19 prevalence is low date: 2020-09-30 words: 1238.0 sentences: 69.0 pages: flesch: 45.0 cache: ./cache/cord-331856-j0gedx43.txt txt: ./txt/cord-331856-j0gedx43.txt summary: In countries with a low prevalence of COVID-19 and a low pre-test probability, confirmation of positive nucleic acid test (NAT) results for SARS-CoV-2 is recommended given the potential for false positive results. [2] [3] [4] Initially, the Public Health Laboratory Network (PHLN) Australia recommended that confirmatory testing be performed on samples where SARS-CoV-2 RNA had been detected to ensure that the result was a true positive. In the context of Australia''s low prevalence of COVID-19 and thus low pre-test probability for infection, we recommend that all positive SARS-CoV-2 NAT results be confirmed by supplementary testing on the original nucleic acid extract and/or re-extraction of nucleic acid from the original sample (if available) and tested using another assay(s) with different gene targets and/or lower limits of detection 10 (Fig. 1) . abstract: nan url: https://doi.org/10.1016/j.pathol.2020.09.009 doi: 10.1016/j.pathol.2020.09.009 id: cord-296219-zzg9hds0 author: Battaglini, Denise title: Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings date: 2020-08-12 words: 7486.0 sentences: 369.0 pages: flesch: 33.0 cache: ./cache/cord-296219-zzg9hds0.txt txt: ./txt/cord-296219-zzg9hds0.txt summary: Within this Abbreviations: ACE2, angiotensin-converting enzyme-2; ANE, acute necrotizing encephalopathy; ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; BBB, blood brain-barrier; CA, Ammon''s horn; CD, cluster of differentiation; CI, confidence interval; CNS, central nervous system; CoV, coronavirus; COVID-19, coronavirus disease 2019; CT, computed tomography; CXCR, chemokine receptor; DIC, disseminated intravascular coagulation; DO 2 , oxygen delivery; DPP4, dipeptidyl dipeptidase-4; ECMO, extracorporeal membrane oxygenation; FiO 2 fraction of inspired oxygen; FOX, forkhead box; HLH, hemophagocytic lymphohistiocytosis; ICAM, intracellular adhesion molecule; ICH, intracerebral hemorrhage; ICP, intracranial pressure; IFN, interferon; MERS, Middle East respiratory syndrome; MHV, mouse hepatitis virus; MRI, magnetic resonance images; nCoV, novel coronavirus; OR, odds ratio; PaCO 2 , partial pressure of carbon dioxide; PaO 2 partial pressure of oxygen; PbtO 2 brain tissue oxygenation tension; PCR, polymerase chain reaction; PEEP, positive end-expiratory pressure; PRES posterior reversible encephalopathy syndrome; RM, recruitment maneuvers; RNA, ribonucleic acid; SARS, severe acute respiratory syndrome; TLRs, toll-like receptor; TMPRSS2 transmembrane serine protease 2; TNF, tumor necrosis factor; WHO, World Health Organization. abstract: In December 2019, an outbreak of illness caused by a novel coronavirus (2019-nCoV, subsequently renamed SARS-CoV-2) was reported in Wuhan, China. Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. Typical manifestations of COVID-19 include fever, dry cough, fatigue, and respiratory distress. In addition, both the central and peripheral nervous system can be affected by SARS-CoV-2 infection. These neurological changes may be caused by viral neurotropism, by a hyperinflammatory and hypercoagulative state, or even by mechanical ventilation-associated impairment. Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain. To date, no studies have taken into consideration the possible secondary effect of mechanical ventilation on brain recovery and outcomes. The aim of our review is to provide an updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiological issues related to brain-lung interactions, and propose strategies for optimization of respiratory support in critically ill patients with SARS-CoV-2 pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/32903391/ doi: 10.3389/fneur.2020.00845 id: cord-352230-8mazd3eu author: Beeraka, Narasimha M. title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 words: 9394.0 sentences: 543.0 pages: flesch: 40.0 cache: ./cache/cord-352230-8mazd3eu.txt txt: ./txt/cord-352230-8mazd3eu.txt summary: Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. COVID-19 is a devastating disease caused by a coronavirus related to the one that caused outbreaks of Severe Acute Respiratory Syndrome (SARS) in the year 2002 (1, 2) . abstract: Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. url: https://doi.org/10.3389/fimmu.2020.552925 doi: 10.3389/fimmu.2020.552925 id: cord-350451-lf27iuwk author: Benedetti, Francesca title: SARS‐CoV‐2: March toward adaptation date: 2020-07-11 words: 1212.0 sentences: 79.0 pages: flesch: 44.0 cache: ./cache/cord-350451-lf27iuwk.txt txt: ./txt/cord-350451-lf27iuwk.txt summary: A third factor still subject of debate is how and how much the mutations observed in SARS-CoV-2 provide an indication of viral fitness and adaptation, and their role first into the initial phases of transmission and now during the reduction of viral spreading. The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel human pathogen, first detected in China quickly became a global health emergency, culminating with the World Health Organization publicly proclaiming the SARS-CoV-2 outbreak as a pandemic (11 March 2020) . Several reports result show that SARS-CoV-2 is rapidly moving across countries, and new mutation hotspots are emerging in different parts of the genome. Although SARS-CoV-2 is less lethal than MERS-CoV, up to 20% of the infected people develop rapidly a severe disease characterized by interstitial pneumonia and acute respiratory distress syndrome that can ultimately lead to death. Davide Zella http://orcid.org/0000-0001-5576-5770 Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant abstract: After an initial period of rising numbers of infected subjected by SARS-CoV-2 and deaths by COVID-19, currently some areas of the World are experiencing a reduction of cases. Different degrees of lockdown and social distancing measures greatly helped in limiting the spread of the disease. The contribution of other external factors like weather conditions and population density, though not as significant, seemed nonetheless to have played an additional role in shaping the course of the epidemic. A third factor still subject of debate is how and how much the mutations observed in SARS-CoV-2 provide an indication of viral fitness and adaptation, and their role first into the initial phases of transmission and now during the reduction of viral spreading. Aim of this commentary is to provide an overview of the status of the pandemic situation linking together the different factors implicated in current situation, and to summarize some strategies that could help us to better manage either a second wave of this virus or a potential new threat of similar nature. This article is protected by copyright. All rights reserved. url: https://doi.org/10.1002/jmv.26233 doi: 10.1002/jmv.26233 id: cord-277076-yvsyo4l9 author: Berger, A. title: SARS date: 2019-09-12 words: 4349.0 sentences: 215.0 pages: flesch: 45.0 cache: ./cache/cord-277076-yvsyo4l9.txt txt: ./txt/cord-277076-yvsyo4l9.txt summary: Measures including source isolation of patientswho only became infectious after onset of clinical symptomsstrict infection control in health care facilities, timely identification and quarantining of exposed contacts, and perhaps also measures to increase social distance, such as travel warnings and screening of travelers, had led to this remarkable and remarkably rapid success. A further, small SARS outbreak occurred again in Guangdong in late 2003/early 2004; molecular analysis of virus isolates from human cases and animals sampled at the same place and time confirmed that this was zoonotically acquired from Paguma larvata. The laboratory diagnosis of SARS remains a challenge; in fact, despite the rapid identification of SARS-CoV as the etiological agent, testing contributed little to the successful control of the 2003 outbreak. A negative antibody test result later than 21 days after the onset of illness is likely to indicate that no infection with SARS-CoV has taken place. abstract: Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases. url: https://api.elsevier.com/content/article/pii/B9780444639516006240 doi: 10.1016/b978-0-444-63951-6.00624-0 id: cord-288484-qy619tfg author: Bernard‐Valnet, R. title: Two patients with acute meningoencephalitis concomitant with SARS‐CoV‐2 infection date: 2020-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In December 2019, a cluster of patients with pneumonia of unknown cause led to the identification of a new strain of pandemic coronavirus called Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS-CoV outbreak, human coronaviruses are known for their neurological tropism. If respiratory complications are at the forefront of clinical presentation of SARS-CoV-2, neurological involvement remains poorly described and understood. We report here two patients infected with SARS-CoV-2 who presented with neurological symptoms and signs. url: https://doi.org/10.1111/ene.14298 doi: 10.1111/ene.14298 id: cord-301974-4wn40ivq author: Berry, Jody D title: Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus date: 2004-09-01 words: 5877.0 sentences: 293.0 pages: flesch: 51.0 cache: ./cache/cord-301974-4wn40ivq.txt txt: ./txt/cord-301974-4wn40ivq.txt summary: A total of 15 l of SARS-CoV antigen (infected Vero cell lysate) or 5 g of highly purified virus is coated (per spot) for 1 h at 37 • C. c Protein specificity tests shown here were determined by Western immunoblot with purified virus and infected cell lysate under denaturing conditions (Fig. 1) . The four Western immunoblot negative, virus-neutralising mAbs were tested for their ability to bind native SARS-CoV in infected cells by immunofluorescence assay. While purified virus is clearly the optimal antigen tested in this series of experiments, the lower quality SARS-CoV-infected Vero cell lysates are, however, much easier to prepare for diagnostic assays. This paper describes the development of murine mAbs which recognise SARS-CoV antigens in ELISA, immuno-dotblot, Western immunoblot, on the surface of infected cells, and in neutralisation assays. abstract: There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development. url: https://www.ncbi.nlm.nih.gov/pubmed/15234813/ doi: 10.1016/j.jviromet.2004.04.009 id: cord-335289-m4u96x2v author: Bhattacharya, Manojit title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach date: 2020-03-05 words: 1017.0 sentences: 81.0 pages: flesch: 49.0 cache: ./cache/cord-335289-m4u96x2v.txt txt: ./txt/cord-335289-m4u96x2v.txt summary: authors: Bhattacharya, Manojit; Sharma, Ashish R.; Patra, Prasanta; Ghosh, Pratik; Sharma, Garima; Patra, Bidhan C.; Lee, Sang‐Soo; Chakraborty, Chiranjib title: Development of epitope‐based peptide vaccine against novel coronavirus 2019 (SARS‐COV‐2): Immunoinformatics approach Therefore, as the situation was getting worse and worse, the need for designing a suitable peptide vaccine component against the SARS-COV-2 was growing. The amino acid sequence of the targeted protein on SARS-COV-2 was collected from the National Centre for Biotechnological Information (NCBI) database. We obtained a total of 34 sequential linear B-cell epitopes of varying lengths from the IEDB server within spike glycoprotein of SARS-COV-2. In this study, we linked the 13 MHC-I and 3 MHC-II antigenic epitopes with (EAAAK) 3 linker peptide to construct a vaccine component. Moreover, the molecular docking of vaccine components with the TLR-5 proves the significance and effectiveness of these epitopes as an ideal vaccine candidate against SARS-COV-2. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach abstract: Recently, a novel coronavirus (SARS‐COV‐2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS‐CoV and MERS‐CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS‐COV‐2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex‐(MHC) I and 3 MHC‐II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll‐like receptor‐5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier. url: https://doi.org/10.1002/jmv.25736 doi: 10.1002/jmv.25736 id: cord-280662-gakayv6e author: Bian, Jingwei title: Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator date: 2020-10-13 words: 5251.0 sentences: 308.0 pages: flesch: 49.0 cache: ./cache/cord-280662-gakayv6e.txt txt: ./txt/cord-280662-gakayv6e.txt summary: Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. SARS-CoV-2 has been shown to share the same functional receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV) 4, 5 . SARS-CoV S-protein binding facilitates ADAM17-dependent ACE2 shedding and has been shown to induce viral entry into the cell 52 . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) abstract: The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies. url: https://doi.org/10.1016/j.apsb.2020.10.006 doi: 10.1016/j.apsb.2020.10.006 id: cord-314793-kb319t4c author: Borroni, Barbara title: Diaphragmatic myoclonus due to SARS-CoV-2 infection date: 2020-10-22 words: 1636.0 sentences: 101.0 pages: flesch: 47.0 cache: ./cache/cord-314793-kb319t4c.txt txt: ./txt/cord-314793-kb319t4c.txt summary: Neurological signs in patients with SARS-CoV-2 have been widely reported, suggesting a neuroinvasive nature of virus [2, 3] . With the present observation, we report two cases of diaphragmatic myoclonus as neurological subacute manifestation of SARS-CoV-2 infection. The Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-020-04766-y) contains supplementary material, which is available to authorized users. Electromyographic recording confirmed rhythmic and synchronous contractions of the diaphragm at 3-Hz frequency as the cause of her abdominal movements (see Fig. 1 ), thus making the diagnosis of diaphragmatic myoclonus or van Leeuwenhoek''s disease [5] . Here, we draw attention to two patients who developed focal diaphragmatic myoclonus after SARS-CoV-2 infection. Indeed, three cases of generalized myoclonus due to SARS-CoV-2 infection have been recently reported [10] . With the present report of two cases, we confirm and extend the neurotropic properties of SARS-CoV-2 virus and point out to a further neurological clinical manifestation of the infection. abstract: A wide range of neurological signs and symptoms have been associated with SARS-CoV-2 infection. In the present report, we described two Italian patients diagnosed with diaphragmatic myoclonus after COVID-19. In both cases, mild lymphocytosis at cerebrospinal fluid analysis and no structural brain changes were reported. The pathophysiological origin of the myoclonus in the two cases was different. In case 1, electroencephalogram did not reveal any cortical correlates and brain imaging of the spine was unremarkable, while in case 2, cortical origin of myoclonus was demonstrated. With the present two cases, we confirm and extend the neurological manifestations of SARS-CoV-2 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10072-020-04766-y) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s10072-020-04766-y doi: 10.1007/s10072-020-04766-y id: cord-317952-4oa9hfb4 author: Bourgonje, Arno R. title: Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19) date: 2020-05-17 words: 12082.0 sentences: 664.0 pages: flesch: 38.0 cache: ./cache/cord-317952-4oa9hfb4.txt txt: ./txt/cord-317952-4oa9hfb4.txt summary: ACE2 was highly expressed on lung alveolar epithelial cells and small intestinal epithelial cells, consistent with potential routes of viral transmission of SARS-CoV-2, as both respiratory and gastrointestinal systems share interfaces with the external environment. ACE2 expression in the lungs and SARS-CoV-2 viral load have been suggested to increase with age, which might provide an explanation to the higher disease severity observed in older patients with COVID-19 [35] . Both SARS-CoV-2 infection, directly mediated by ACE2 expression and activity, and superimposed disease triggers may be responsible for the observed pathological findings. Additionally, another study reported purpura and livedo racemosa in several severely affected COVID-19 patients with small vessel thrombosis with co-localization of complement and SARS-CoV-2 spike proteins on histopathology [148] .This indicates direct viral infection of the small skin vessels. Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone-inhibitors: Potential implications for coronavirus SARS-CoV-2 infected patients abstract: Angiotensin‐converting enzyme‐2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin‐angiotensin‐aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. This article is protected by copyright. All rights reserved. url: https://doi.org/10.1002/path.5471 doi: 10.1002/path.5471 id: cord-272654-hh29olk7 author: Bošnjak, Berislav title: Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods date: 2020-11-02 words: 6111.0 sentences: 414.0 pages: flesch: 54.0 cache: ./cache/cord-272654-hh29olk7.txt txt: ./txt/cord-272654-hh29olk7.txt summary: We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Similarly, anti-SARS-CoV-2 S IgA antibodies were present in 33/37 (89.2%) of the tested sera; two samples were diagnosed as borderline positive and two as negative Fig. 1 Qualitative analysis of serum total IgG (A) and IgA (B) antibodies against SARS-CoV-2 S1 in convalescent patients with mild or severe COVID-19 and healthy controls (HC) determined by ELISA. The median sVNT titer of the mildly affected convalescent cohort was 1:180, indicating that patients with mild COVID-19 produce relatively low amounts of SASRS-CoV-2 neutralizing antibodies (Fig. 2H ). This hypothesis is further supported by a positive correlation between the duration of symptoms and total anti-SARS-CoV-2 IgG, but not IgA, antibodies in convalescent patients with mild disease (Fig. 5A, B) . abstract: Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy. url: https://doi.org/10.1038/s41423-020-00573-9 doi: 10.1038/s41423-020-00573-9 id: cord-256888-tdx12ccj author: Bradley, Benjamin T title: Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series date: 2020-07-16 words: 5006.0 sentences: 300.0 pages: flesch: 45.0 cache: ./cache/cord-256888-tdx12ccj.txt txt: ./txt/cord-256888-tdx12ccj.txt summary: To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. 8 Post-mortem studies have shown pulmonary, renal, and small vessel injury, with particles resembling virus observed in the kidney by electron microscopy. By electron microscopy, aggregates of uniform, round enveloped particles ranging in size from around 70 nm to 100 nm with peripheral spike-like projections consistent with the morphology described for SARS-CoV-2 were observed in the lung, trachea, kidney, and large intestine of patient 8 and patient 13. [9] [10] [11] [12] We present a case series of autopsy findings in 14 patients who died after SARS-CoV-2 infection. The major histopathological observation in our series of patients who died with COVID-19 was diffuse alveolar damage-type lung injury in the acute or organising phases (12 [86%] of 14 patients). abstract: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None. url: https://doi.org/10.1016/s0140-6736(20)31305-2 doi: 10.1016/s0140-6736(20)31305-2 id: cord-300716-urmogf97 author: Briguglio, Matteo title: Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes date: 2020-06-05 words: 9889.0 sentences: 460.0 pages: flesch: 42.0 cache: ./cache/cord-300716-urmogf97.txt txt: ./txt/cord-300716-urmogf97.txt summary: The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. Keywords: smell, olfactory bulb, coronavirus, SARS-CoV-2, COVID-19, infections, virulence, host pathogen interactions THE SNIFFING OUT OF CORONAVIRUSES Named after their crown-like spikes, coronaviruses are large non-segmented single-stranded positive-sense enveloped RNA viruses that may spill out from animals to infect humans and cause respiratory diseases. It is urgent to discuss whether SARS-CoV-2 can gain access to the central nervous system through a nasal-nervous pathway or other routes and if the fatal respiratory failure may be associated with a neuronal injury in critical brain areas of the host. abstract: The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation- and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers. url: https://www.ncbi.nlm.nih.gov/pubmed/32581854/ doi: 10.3389/fphys.2020.00671 id: cord-325959-uqg2xkie author: Bundschuh, Christian title: Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma date: 2020-06-08 words: 2208.0 sentences: 125.0 pages: flesch: 57.0 cache: ./cache/cord-325959-uqg2xkie.txt txt: ./txt/cord-325959-uqg2xkie.txt summary: METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. low "false" positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes Coronavirus Disease 2019 (COVID-19), has recently emerged to cause a human pandemic. For the clinical evaluation we measured SARS-CoV-2 IgM and IgG antibodies in three different cohorts: First in a "positive cohort" of patients with SARS-CoV-2 RT-PCR confirmed 5 COVID-19 with serial blood samples at different time points from symptom onset. Furthermore, the clinical evaluation study demonstrated high "true" positivity rates in the SARS-CoV-2 RT-PCR confirmed COVID-19 patients with symptom onset after 15 days with 94.4% for IgM and 100% for IgG SARS-CoV-2 abstract: BACKGROUND: Besides SARS-CoV-2 RT-PCR testing, serological testing is emerging as additional option in COVID-19 diagnostics. Aim of this study was to evaluate novel immunoassays for detection of SARS-CoV-2 antibodies in human plasma. METHODS: Using EDI(TM) Novel Coronavirus COVID-19 Enzyme Linked Immunosorbent Assays (ELISAs), we measured SARS-CoV-2 IgM and IgG antibodies in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: The positivity rates in the COVID-19 patients were 5.9% for IgM and 2.9% for IgG ≤5 days after symptom onset; Between day 5 and day 10 the positivity rates were 37.1% for IgM and 37.1% for IgG and rose to 76.4% for IgM and 82.4% for IgG after >10-15 days. After 15-22 days the “true” positivity rates were 94.4% for IgM and 100% for IgG. The “false” positivity rates were 0.5% for IgM and 1.0% for IgG in the healthy blood donors, 1.6% for IgM and 1.2% for IgG in ICU patients. CONCLUSIONS: This study shows high “true” vs. low “false” positivity rates for the EDI(TM) SARS-CoV-2 IgM and IgG ELISAs. url: https://doi.org/10.1016/j.cca.2020.05.047 doi: 10.1016/j.cca.2020.05.047 id: cord-348384-8cvt1fo6 author: Butsashvili, M. title: Knowledge of novel coronavirus (SARS-COV-2) among a Georgian population date: 2020-05-19 words: 1988.0 sentences: 120.0 pages: flesch: 54.0 cache: ./cache/cord-348384-8cvt1fo6.txt txt: ./txt/cord-348384-8cvt1fo6.txt summary: This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus and perceptions of preventive measures among the Georgian population, including health care workers (HCWs). We collected information on demographic data (age, gender, marital status, education, employment status), knowledge of symptoms and transmission modes of coronavirus, perceived differences between coronavirus and influenza, availability of antiviral medication and vaccination. In response to the question "Are you afraid of getting infected with SARS-COV-2?" almost half of study participants (46.3%) said "no." The majority of survey respondents correctly identified the transmission route and symptoms of the new coronavirus (96.9% and 98.0%, respectively). abstract: Introduction Georgia confirmed its first case of SARS-COV-2 infection on February 26, 2020 and by March 31, a total of 110 cases have been reported. Limited understanding about epidemics can lead to panic and disrupt public health efforts to contain transmission. It is important to understand perceptions of the population regarding the disease. This study reports results of a survey designed to understand attitudes and knowledge regarding SARS-COV-2 virus among Georgian population, including health care workers (HCWs). Materials and methods The online survey was conducted using a Facebook advertisement. The target was the whole country and the language used was Georgian. We collected information on demographic data, knowledge of the disease, including perceived differences between coronavirus and influenza. We also included questions to capture the populations perceptions about government preparedness to combat the new coronavirus. Results The survey was open for three days (March 2-4, 2020). 5228 participants completed the survey. Of these, 40.3% were 25-45 years old, 58.2% were female, 20.7% had university degree and 10.3% were HCWs. For 25.8% of respondents, COVID-19 and influenza are the same diseases; 10.9% did not know if they are different. The majority correctly identified the transmission route and symptoms (96.9% and 98.0%, respectively). 19.1% think that Georgia is ready for COVID 19 epidemic, while according to 55% the county is not ready, but HCWs are trying hard to respond properly. For 18% response is inadequate. There was no difference in knowledge between HCWs, non-HCWs and unemployed. 20% of HCWs as well as other study subjects believe that SARS-COV-2 vaccine and medications do exist but are simply not available in Georgia. Conclusion Given that information regarding coronavirus is changing very rapidly, the need to reach people with time-sensitive educational messages as well as prevention strategies is vital. url: http://medrxiv.org/cgi/content/short/2020.05.14.20101642v1?rss=1 doi: 10.1101/2020.05.14.20101642 id: cord-304263-5kddk5fa author: C., Selvaa Kumar title: Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2 date: 2020-10-08 words: 3768.0 sentences: 252.0 pages: flesch: 56.0 cache: ./cache/cord-304263-5kddk5fa.txt txt: ./txt/cord-304263-5kddk5fa.txt summary: In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence. Research studies unveiled the interaction between the structural spike 1 (S1) protein of SARS-CoV-2 with the nicotinic acetylcholine receptors (nAChRs) that are likely to intervene with its biological function (20, 21) . Thus, the insilico study performed to unveil the nicotine''s urge for binding with the soluble ACE2 with or without SARS-CoV-2 in compliance with its interaction with the known human neuronal alpha4-beta2 nicotine-acetylcholine receptor (nN-AChR). We found the reported structural protein template of ACE2-SARS-CoV-2 complex with the enlisted PDB ID: 6VW1 (24) incomplete with numerous missing amino acid residues. Structural binding characteristics of nicotine with the soluble angiotensinconverting enzyme 2 (sACE2)-SARS-CoV-2 complex in the context of its interaction with the neuronal nicotinic acetylcholine receptor (nN-AChR). abstract: The study aimed to validate the proficiency of nicotine binding with the soluble angiotensin-converting enzyme II receptor (sACE2) with or without SARS-CoV-2 in the context of its binding affinity. Modelled human sACE2 and the spike (S1) protein of Indian SARS-CoV-2 (INS1) docked with each other. On the other hand, nicotine docked with sACE2 in the presence or absence of SARS-CoV-2. Nicotine established a stable interaction with negatively charged Asp368 of sACE2, which in turn binds with amino acids like Thr362, Lys363, Thr365, Thr371, and Ala372. In the presence of nicotine, INS1 and sACE2 showed a reduced binding affinity score of -12.6 kcal/mol (Vs -15.7 kcal/mol without nicotine), and a lowered interface area of 1933.6 Å(2) (Vs 2057.3Å(2) without nicotine). The neuronal nicotinic acetylcholine receptor and angiotensin-converting enzyme 2 (ACE2) receptor showed 19.85 % sequence identity among themselves. Following these receptors possessed conserved Trp302 and Cys344 amino acids between them for nicotine binding. However, nicotine showed a higher binding affinity score of -6.33 kcal/mol for the sACE2-INS1 complex than the sACE2 alone with -5.24 kcal/mol. A lowered inhibitory constant value of 22.95µM recorded while nicotine interacted with the sACE2-INS1 complex over the sACE2 alone with 151.69 µM. In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence. url: https://www.ncbi.nlm.nih.gov/pubmed/33052306/ doi: 10.1016/j.toxrep.2020.10.002 id: cord-303517-8971aq02 author: Cajamarca-Baron, Jairo title: SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression date: 2020-10-16 words: 9096.0 sentences: 459.0 pages: flesch: 45.0 cache: ./cache/cord-303517-8971aq02.txt txt: ./txt/cord-303517-8971aq02.txt summary: 27, 28 Among other comorbidities, chronic kidney disease is associated with in-hospital mortality, as are cancer and cerebrovascular disease, demonstrated through two meta-analyses that included over fifteen thousand patients ( Table 2) ; studies suggest that superficial fungal infections and psoriasis confer vulnerability to COVID-19; a body mass index (BMI) > 40 kg/m2 is an independent risk factor for complications from the infection; and there are discouraging results regarding underlying neurological disease and SARS-CoV-2. It is even possible that such disease-modifying therapies and their immunosuppressive effect may play a protective role during 19-COVID infection by preventing or dampening hyperimmune activity that, in some cases, could lead to clinical deterioration; there is even a report of a patient with primary progressive multiple sclerosis receiving treatment with ocrelizumab and becoming infected with SARS-CoV-2, in the context of lymphopenia and hypogammaglobulinema expected for this type of treatment, without generating major clinical complications, this hypothesis is obviously limited for now only to academic deductions and limited information. abstract: Background It is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people. Objective To carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies. Results Patients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis (MS), neuromyelitis optica (NMODS), myasthenia gravis (MG)), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes. Conclusion Given the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer. url: https://api.elsevier.com/content/article/pii/S2173574320301295 doi: 10.1016/j.reumae.2020.08.001 id: cord-293890-thfros7x author: Carbo, Ellen C. title: Coronavirus discovery by metagenomic sequencing: a tool for pandemic preparedness date: 2020-08-21 words: 2315.0 sentences: 129.0 pages: flesch: 49.0 cache: ./cache/cord-293890-thfros7x.txt txt: ./txt/cord-293890-thfros7x.txt summary: METHODS: The performance of a viral metagenomic protocol in a clinical setting for the identification of novel coronaviruses was tested using clinical samples containing SARS-CoV-2, SARS-CoV, and MERS-CoV, in combination with databases generated to contain only viruses of before the discovery dates of these coronaviruses, to mimic virus discovery. Additionally, the efficacy of detection of novel coronaviruses using capture probes targeting vertebrate viruses [10] [11] known before the current pandemic was analyzed using a SARS-CoV-2 clinical sample. After extraction of human reads, FASTQ files generated for SARS-CoV-2 samples (with and without viral enrichment) were uploaded for classification and de novo assembly by the commercial webbased tool Genome Detective v1.120 (www.genomedetective.com, accessed 2020-05-11) [9] , using a reference database (generated 2019-09-21). In this study, we evaluated the performance of a metagenomic sequencing protocol for the identification of emerging viruses using clinical samples in combination with a simulated reference database. abstract: INTRODUCTION: The SARS-CoV-2 pandemic of 2020 is a prime example of the omnipresent threat of emerging viruses that can infect humans. A protocol for the identification of novel coronaviruses by viral metagenomic sequencing in diagnostic laboratories may contribute to pandemic preparedness. AIM: The aim of this study is to validate a metagenomic virus discovery protocol as a tool for coronavirus pandemic preparedness. METHODS: The performance of a viral metagenomic protocol in a clinical setting for the identification of novel coronaviruses was tested using clinical samples containing SARS-CoV-2, SARS-CoV, and MERS-CoV, in combination with databases generated to contain only viruses of before the discovery dates of these coronaviruses, to mimic virus discovery. RESULTS: Classification of NGS reads using Centrifuge and Genome Detective resulted in assignment of the reads to the closest relatives of the emerging coronaviruses. Low nucleotide and amino acid identity (81% and 84%, respectively, for SARS-CoV-2) in combination with up to 98% genome coverage were indicative for a related, novel coronavirus. Capture probes targeting vertebrate viruses, designed in 2015, enhanced both sequencing depth and coverage of the SARS-CoV-2 genome, the latter increasing from 71 to 98%. CONCLUSION: The model used for simulation of virus discovery enabled validation of the metagenomic sequencing protocol. The metagenomic protocol with virus probes designed before the pandemic, can assist the detection and identification of novel coronaviruses directly in clinical samples. url: https://api.elsevier.com/content/article/pii/S138665322030336X doi: 10.1016/j.jcv.2020.104594 id: cord-308252-qwoo7b1l author: Cardinale, Vincenzo title: Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis date: 2020-09-16 words: 4596.0 sentences: 229.0 pages: flesch: 36.0 cache: ./cache/cord-308252-qwoo7b1l.txt txt: ./txt/cord-308252-qwoo7b1l.txt summary: During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Since inflammation seems to upregulate ACE2 expression [17] , it is important to understand whether patients with inflammatory bowel disease (IBD) are more susceptible to Covid-19 and the cytokine release syndrome (CRS) associated with lung injury and fatal outcome [21] . While the risk of SARS-CoV-2 infection in IBD patients depends on several universal risk factors, including social distancing [22] , older age and comorbidities have been associated with a negative outcome in IBD, whereas IBD treatments have not, highlighting that acute IBD flare prevention and inflammation reduction may avoid severe Covid-19 [23] . abstract: The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice. url: https://api.elsevier.com/content/article/pii/S1590865820304692 doi: 10.1016/j.dld.2020.09.009 id: cord-326013-5i35zdmv author: Carpinteiro, Alexander title: Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells date: 2020-10-29 words: 3113.0 sentences: 175.0 pages: flesch: 47.0 cache: ./cache/cord-326013-5i35zdmv.txt txt: ./txt/cord-326013-5i35zdmv.txt summary: The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection. Pretreatment of the cells with 5, 10, 20, or 25 µM amitriptyline prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike for 30 min (Fig. 3B, Fig. 4A ). Treating Vero cells with neutralizing antibodies to spike or with recombinant ACE2 protein prevented the activation of acid sphingomyelinase and the release of ceramide upon infection with pp-VSV-SARS-CoV-2 spike (Fig. 3B, Fig. 4A Amitriptyline and other drugs with similar structure and properties have been clinically used for many years (since 1962) to treat patients with depressive disorder. Best results were obtained with venlafaxin, fluoxetine, escitalopram and mirtazipine, drugs that were also shown in the present study to inhibit acid sphingomyelinase and ceramide release upon pp-VSV-SARS-CoV-2 spike infection. abstract: The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline, or genetic downregulation of the enzyme prevents infection of cultured cells or freshy isolated human nasal epithelial cells with SARS-CoV-2 or pseudoviral pp-VSV-SARS-CoV-2 particles expressing spike, a bona fide system mimicking SARS-CoV-2 infection. Infection activates acid sphingomyelinase and triggers a release of ceramide on the cell surface. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treating volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike. The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/33163980/ doi: 10.1016/j.xcrm.2020.100142 id: cord-354597-xubsodnk author: Carvalho, Alexandre title: SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease date: 2020-04-17 words: 2779.0 sentences: 159.0 pages: flesch: 47.0 cache: ./cache/cord-354597-xubsodnk.txt txt: ./txt/cord-354597-xubsodnk.txt summary: Recent reports from China have described concomitant digestive symptoms, such as nausea, vomiting, diarrhea, and abdominal pain, in patients with confirmed SARS-CoV-2 pulmonary infection (5) (6) (7) (8) and the presence of SARS-CoV-2 RNA in fecal samples (8, 9) . We present a case of SARS-CoV-2 gastrointestinal infection causing acute hemorrhagic colitis and signaling COVID-19 disease which endoscopy confirmed colonic injury and helped exclude other etiologies of disease. On hospital day 4, 9 days after the onset of her digestive symptoms, the patient developed a cough; nasopharyngeal swabs were sent for comprehensive viral detection, including SARS-CoV-2 RNA (Quest Diagnostics). Given the patient''s elevated C-reactive protein and persistent abdominal pain and bloody diarrhea, a flexible sigmoidoscopy was performed on hospital day 4 to evaluate for evidence of inflammatory bowel disease or ischemic colitis. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32496741/ doi: 10.14309/ajg.0000000000000667 id: cord-323666-t7cshj05 author: Cegolon, L. title: Nasal Disinfection for the Prevention and Control of COVID-19: A Scoping Review on Potential Chemo-preventive Agents. date: 2020-08-18 words: 6187.0 sentences: 339.0 pages: flesch: 46.0 cache: ./cache/cord-323666-t7cshj05.txt txt: ./txt/cord-323666-t7cshj05.txt summary: Figure 1 reports the corresponding changes as percentage or odds; the latter detects the improvement of the index score better than the former because it is able to overcome the ceiling effects J o u r n a l P r e -p r o o f Therefore, in addition to an effective treatment for symptomatic patients, there is an urgent need to abate the carriage of SARS-CoV-2 in the human nasal cavity of asymptomatic/pre-symptomatic individuals, in order to contain the transmission of the novel coronavirus within the community. The abstracts of the original articles were explored for the following terms: mechanism(s) of action, tolerability and any evidence of toxic effects or selection of resistant strains, whether the treatment was tested in vitro (in particular against SARS-CoV-2), or reached the clinical trials stage, or is currently marketed/promoted/sold. abstract: BACKGROUND: Neither pre-exposure nor post-exposure chemo-prophylaxis agents are currently available to prevent COVID-19. On the other hand, high loads of SARS-CoV-2 are shed from the nasal cavity before and after symptoms onset. OBJECTIVE: To conduct a scoping review on the available evidence on tolerable nasal disinfectants with encouraging health outcomes against SARS-CoV-2, i.e., agents effective against at least two different viruses beyond SARS-CoV-2. METHODS: Online databases were searched to identify papers published during 2010–2020. Publications were selected if they were relevant to the scoping review. The review was narrative, describing for each treatment the mechanism(s) of action, tolerability, in vitro and in vivo evidence of the effects against SARS-CoV-2 and whether the product had been marketed. RESULTS: Eight treatments were scrutinized: hypothiocyanite, lactoferrin, N-chlorotaurine, interferon-alpha, povidone-iodine, quaternary ammonium compounds, alcohol-based nasal antiseptics and hydroxychloroquine. In vitro viricidal effect against SARS-CoV-2 was reported for povidone-iodine. Inhibition of other coronaviruses was described for lactoferrin, hydroxychloroquine and quaternary ammonium compound. No treatment has been tested against SARS-CoV-2 in randomized controlled clinical trials thus far. However, interferon-alpha, lactoferrin and hydroxychloroquine were tested in one-arm open label uncontrolled clinical trials. Oxidant activity (hypothiocyanite, N-chlorotaurine and povidone-iodine), enhancement of endocytic and lysosomal pH (quaternary ammonium compounds and hydroxychloroquine) and destruction of the viral capsid (quaternary ammonium compounds, alcohol-based nasal antiseptics) were the main mechanisms of action. Lactoferrin and interferon-alpha had subtle biological mechanisms. With the exception of N-chlorotaurine, the others are products available on the market. CONCLUSIONS: Effective and safe chemo-prophylactic drugs against SARS-CoV-2 do not exist yet but most eligible candidates are already in the market. Whilst the human nasal cavity is the port of entry for SARS-CoV-2, the mouth is involved as exit site through emission of respiratory droplets. The well-known hand-to-nose-to-hand cycle of contamination requires appropriate additional strategies for infection control. To narrow down the subsequent laboratory and clinical investigations, a case-control approach could be employed to compare the use of candidate drugs among individuals testing positive and negative to COVID-19 swabs. url: https://api.elsevier.com/content/article/pii/S1438463920305514 doi: 10.1016/j.ijheh.2020.113605 id: cord-283709-y59h5bw8 author: Chan, Renee W Y title: Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study date: 2014-08-28 words: 4858.0 sentences: 225.0 pages: flesch: 53.0 cache: ./cache/cord-283709-y59h5bw8.txt txt: ./txt/cord-283709-y59h5bw8.txt summary: We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. INTERPRETATION: The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with the prototype human MERS-CoV EMC strain to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. To assess the infection potential of dromedary camel Middle East respiratory syndrome coronavirus (MERS-CoV) strains for humans, genetic analysis should be complemented with phenotypic characterisation in physiologically relevant invitro cell cultures. abstract: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the Arabian peninsula, and is a global concern for public health. Limited human-to-human transmission, leading to some case clusters, has been reported. MERS-CoV has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. METHODS: We characterised MERS-CoV viruses from dromedaries in Saudi Arabia and Egypt and compared them with a human MERS-CoV reference strain. We assessed viral replication kinetics and competence in Vero-E6 cells (rhesus monkey), tissue tropism in cultures of ex-vivo human bronchial and lung tissues, and cytokine and chemokine induction, gene expression, and quantification of viral RNA in Calu-3 cells (human respiratory tract). We used mock-infected tissue as negative controls for ex-vivo experiments and influenza A H5N1 as a positive control for cytokine and chemokine induction experiments in Calu-3 cells. FINDINGS: We isolated three dromedary strains, two from Saudi Arabia (Dromedary/Al-Hasa-KFU-HKU13/2013 [AH13] and Dromedary/Al-Hasa-KFU-HKU19D/2013 [AH19D]), and one from Egypt (Dromedary/Egypt-NRCE-HKU270/2013 [NRCE-HKU270]). The human and dromedary MERS-CoV strains had similar viral replication competence in Vero-E6 cells and respiratory tropism in ex-vivo cultures of the human respiratory tract, and had similar ability to evade interferon responses in the human-respiratory-tract-derived cell line Calu-3. INTERPRETATION: The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. Exposure to zoonotic MERS-CoV is probably occurring in a wider geographical region beyond the Arabian peninsula. FUNDING: King Faisal University, Egyptian National Research Centre, Hong Kong Food and Health Bureau, National Institute of Allergy and Infectious Diseases, and European Community Seventh Framework Program. url: https://www.sciencedirect.com/science/article/pii/S2213260014701584 doi: 10.1016/s2213-2600(14)70158-4 id: cord-320619-r466dc5t author: Chand Dakal, Tikam title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 date: 2020-11-05 words: 3843.0 sentences: 210.0 pages: flesch: 46.0 cache: ./cache/cord-320619-r466dc5t.txt txt: ./txt/cord-320619-r466dc5t.txt summary: title: SARS-CoV-2 Attachment to Host Cells is Possibly Mediated via RGD-Integrin Interaction in a Calcium-dependent Manner and Suggests Pulmonary EDTA Chelation Therapy as a Novel Treatment for COVID 19 The higher expression of integrins in lungs along with their previously known high binding affinity (∼K(D) = 4.0nM) for virus RGD motif could serve as a possible explanation for high infectivity of SARS-CoV-2. This study is the first study to present striking evidence (substantiated by existing facts in literature) favoring the role of calcium and other divalent ions (magnesium, manganese etc.) in RGD-integrins mediated virus attachment with the host cells for and that lowering the concentration of calcium and other divalent ions in lungs could be a possible mechanism to avert SARs-CoV-2 infection and invasion. A number of motifs were predicted in the spike protein sequence such as RGD (from 403-405 aa in receptor binding domain of SARS-CoV-2) ( Table 2 ). abstract: SARS-CoV-2 is a highly contagious virus that has caused serious health crisis world-wide resulting into a pandemic situation. As per the literature, the SARS-CoV-2 is known to exploit humanACE2 receptors (similar toprevious SARS-CoV-1) for gaining entry into the host cell for invasion, infection, multiplication and pathogenesis. However, considering the higher infectivity of SARS-CoV-2 along with the complex etiology and pathophysiological outcomes seen in COVID-19 patients, it seems that there may be an alternate receptor for SARS-CoV-2. I performed comparative protein sequence analysis, database based gene expression profiling, bioinformatics based molecular docking using authentic tools and techniques for unveiling the molecular basis of high infectivity of SARS-CoV-2 as compared to previous known coronaviruses. My study revealed that SARS-CoV-2 (previously known as 2019-nCoV) harbors a RGD motif in its receptor binding domain (RBD) and the motif is absent in all other previously known SARS-CoVs. The RGD motif is well known for its role in cell-attachment and cell-adhesion. My hypothesis is that the SARS-CoV-2 may be (via RGD) exploiting integrins, that have high expression in lungs and all other vital organs, for invading host cells. However, an experimental verification is required. The expression of ACE2, which is a known receptor for SARS-CoV-2, was found to be negligible in lungs. I assume that higher infectivity of SARS-CoV-2 could be due to this RGD-integrin mediated acquired cell-adhesive property. Gene expression profiling revealed that expression of integrins is significantly high in lung cells, in particular αvβ6, α5β1, αvβ8 and an ECM protein, ICAM1. The molecular docking experiment showed the RBD of spike protein binds with integrins precisely at RGD motif in a similar manner as a synthetic RGD peptide binds to integrins as found by other researchers. SARS-CoV-2 spike protein has a number of phosphorylation sites that can induce cAMP, PKC, Tyr signaling pathways. These pathways either activate calcium ion channels or get activated by calcium. In fact, integrins have calcium & metal binding sites that were predicted around and in vicinity of RGD-integrin docking site in our analysis which suggests that RGD-integrins interaction possibly occurs in calcium-dependent manner. The higher expression of integrins in lungs along with their previously known high binding affinity (∼K(D) = 4.0nM) for virus RGD motif could serve as a possible explanation for high infectivity of SARS-CoV-2. On the contrary, human ACE2 has lower expression in lungs and its high binding affinity (∼K(D)= 15nM) for spike RBD alone could not manifest significant virus-host attachment. This suggests that besides human ACE2, an additional or alternate receptor for SARS-CoV-2 is likely to exist. A highly relevant evidence never reported earlier which corroborate in favor of RGD-integrins mediated virus-host attachment is an unleashed cytokine storm which causes due to activation of TNF-α and IL-6 activation; and integrins role in their activation is also well established. Altogether, the current study has highlighted possible role of calcium and other divalent ions in RGD-integrins interaction for virus invasion into host cells and suggested that lowering divalent ion in lungs could avert virus-host cells attachment. url: https://api.elsevier.com/content/article/pii/S017129852030543X doi: 10.1016/j.imbio.2020.152021 id: cord-310221-car394ou author: Chandrashekar, Abishek title: SARS-CoV-2 infection protects against rechallenge in rhesus macaques date: 2020-05-20 words: 2540.0 sentences: 140.0 pages: flesch: 44.0 cache: ./cache/cord-310221-car394ou.txt txt: ./txt/cord-310221-car394ou.txt summary: We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. On day 2 following challenge, both necropsied animals demonstrated multifocal regions of inflammation and evidence of viral pneumonia, including expansion of alveolar septae with mononuclear cell infiltrates, consolidation, and edema (Fig. 3, A and B) . SARS-CoV-2 infection in rhesus macaques led to humoral and cellular immune responses (Fig. 2) and provided protection against rechallenge (Fig. 5) . In summary, SARS-CoV-2 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against SARS-CoV-2 rechallenge. abstract: An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates. url: https://www.ncbi.nlm.nih.gov/pubmed/32434946/ doi: 10.1126/science.abc4776 id: cord-347460-9vechh4x author: Chang, Feng-Yee title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 words: 8050.0 sentences: 384.0 pages: flesch: 43.0 cache: ./cache/cord-347460-9vechh4x.txt txt: ./txt/cord-347460-9vechh4x.txt summary: Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] . abstract: On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease. url: https://doi.org/10.1186/s12929-020-00663-w doi: 10.1186/s12929-020-00663-w id: cord-335137-5qt286kc author: Chatterjee, Swapan K. title: Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19 date: 2020-08-11 words: 7124.0 sentences: 369.0 pages: flesch: 47.0 cache: ./cache/cord-335137-5qt286kc.txt txt: ./txt/cord-335137-5qt286kc.txt summary: It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. The most significant surface protein is spike glycoprotein which interferes in establishing the association between the human respiratory epithelial cells to the virus via cell surface membrane receptor angiotensin-converting enzyme 2 (ACE2) and finally establishes the host tropism (Li et al., 2003) . A recent study suggests that prediction of SARS-CoV-2 spike glycoprotein structure, glycan shield pattern and pattern of glycosylation has great inference on understanding the viral camouflage as well as the outline of cell entry, and also facilitate the development of new small-molecule drugs, vaccines, antibodies, and screening of the human host targets (Song et al., 2018) . Various studies have proved that SARS-CoV-2 infection initiation and spread of disease into the host cells mainly depends upon S protein priming by TMPRSS2 (Transmembrane protease serine type 2), the serine protease. abstract: The coronavirus disease 2019 (COVID-19), is a highly contagious transmittable disease caused by a recently discovered coronavirus, pathogenic SARS-CoV-2. Followed by the emergence of highly pathogenic coronaviruses in 2003 SARS-CoV, in 2012 MERS-CoV, now in 2019 pathogenic SARS-CoV-2, is associated with a global “pandemic” situation. In humans, the effects of these viruses are correlated with viral pneumonia, severe respiratory tract infections. It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. ACE2 receptor is highly expressed in airway epithelial cells. Along with viral-receptor interaction, proteolytic cleavability of S protein has been considered as the determinant of disease severity. Several studies highlight the occurrence of impaired host immune response and expression of excessive inflammatory response especially cytokines against viral infection. The mechanisms of SARS-CoV-2 induced acute lung injury are still undefined; however, the term cytokine storm has now been recognized to be closely associated with COVID-19. The levels of inflammatory mediators from cytokine storm cause damage to the host cells. In particular, the proinflammatory cytokine IL-6 appears to be the key mediator in early phase of virus-receptor interaction; however, secreted IL-6 might not be representative of lung inflammation. Understanding the cellular, and molecular factors involved in immune dysregulation and the high virulence capacity of COVID-19 will help in potential targeted therapy against it. “Drug repurposing” and “molecular docking analysis” is considered as an attractive alternative approach in analyzing suitable drug candidates to combat SARS-CoV-2 infection. Globally, extensive research is in progress to discover a new vaccine for novel COVID-19. Moreover, our review mainly focuses on the most state-of-the-art therapeutic approach mediated by “Mannose-binding lectin (MBL).” One of the most significant molecules of innate immunity is MBL. It plays a major role in the activation of the complement system as an ante-antibody prior to the response of any particular antibody. Recombinant human MBL can be used as immunomodulators against SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32850977/ doi: 10.3389/fmolb.2020.00196 id: cord-340042-intxyu46 author: Chaudhry, Sundas Nasir title: New insight on possible vaccine development against SARS-CoV-2 date: 2020-09-11 words: 5457.0 sentences: 260.0 pages: flesch: 43.0 cache: ./cache/cord-340042-intxyu46.txt txt: ./txt/cord-340042-intxyu46.txt summary: In December 2019, a novel virus, namely COVID-19, caused by SARS-CoV-2, developed from Wuhan, Hubei territory of China, which used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Different subunits of spike proteins like the S1 and S2 subunits, and the receptor-binding domain (RBD) are the critical elements for the formation of a vaccine against the newly emerged virus that helped in producing T cell responses and protective immunity against SARS-CoV-2 [29] . The recombinant protein is known as one of the emerging fields for the development of a vaccine against viruses due to several properties including tight binding to specific ACE-2 receptor, provoke immune protection against viral infections, increase antibody-dependent viral entry, and promote antigenicity against virus like SARS-CoV [52] . abstract: In December 2019, a novel virus, namely COVID-19, caused by SARS-CoV-2, developed from Wuhan, Hubei territory of China, which used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32926920/ doi: 10.1016/j.lfs.2020.118421 id: cord-337825-ujq9mxk7 author: Chen, Bin title: Overview of lethal human coronaviruses date: 2020-06-10 words: 13423.0 sentences: 761.0 pages: flesch: 51.0 cache: ./cache/cord-337825-ujq9mxk7.txt txt: ./txt/cord-337825-ujq9mxk7.txt summary: Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine abstract: Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus–host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment. url: https://doi.org/10.1038/s41392-020-0190-2 doi: 10.1038/s41392-020-0190-2 id: cord-031079-9lxhvyyb author: Chen, Li title: The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review date: 2020-07-27 words: 5660.0 sentences: 354.0 pages: flesch: 47.0 cache: ./cache/cord-031079-9lxhvyyb.txt txt: ./txt/cord-031079-9lxhvyyb.txt summary: CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which is mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular system. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to be further elucidated. CQ and its more soluble and less toxic metabolite HCQ are primarily used for prophylaxis and treatment of malaria, but they have also been reported to effectively inhibit the effects of certain viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N. 40, 41 Several studies have reported that 3% to 29% of COVID-19 patients develop acute respiratory distress syndrome (ARDS) which is a common complication and cause of death as a result of SARS-CoV-2 infection. abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and there is currently no effective antiviral therapy. It has been suggested that Chloroquine (CQ) and hydroxychloroquine (HCQ), which were primarily employed as prophylaxis and treatment for malaria, could be used to treat COVID-19. CQ and HCQ may be potential inhibitors of SARS-CoV-2 entry into host cells, which is mediated via the angiotensin-converting enzyme 2 (ACE2), and may also inhibit subsequent intracellular processes which lead to COVID-19, including damage to the cardiovascular system. However, paradoxically, CQ and HCQ have also been reported to cause damage to the cardiovascular system. In this review, we provide a critical examination of the published evidence. CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ and HCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to be further elucidated. However, even if it were to turn out that CQ and HCQ are not useful drugs in practice, further studies of their mechanism of action could be helpful in improving our understanding of COVID-19 pathology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454642/ doi: 10.1093/function/zqaa012 id: cord-300041-1d9xu4ts author: Chen, Sharon C-A title: Focus on SARS-CoV-2 and COVID-19 date: 2020-10-08 words: 1024.0 sentences: 60.0 pages: flesch: 52.0 cache: ./cache/cord-300041-1d9xu4ts.txt txt: ./txt/cord-300041-1d9xu4ts.txt summary: In contrast, more recent pandemics have been dominated by viruses such as influenza H1N1 and H3N2, localised epidemics by Ebola virus, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), MERS-CoV, and now, SARS-CoV-2, the causative agent of COVID-19. However, by having a single edition, with broad focus on human pathology of SARS-CoV-2 infection, we aim to provide the readers of Pathology with insights from different areas of COVID-19 diagnosis. 2 Substantive progress continues to be made in the arena of diagnostic tests for SARS-CoV-2 infection with improvements in molecular diagnostics, rapid antigen detection tests and serological assays. We continue to be faced by the risk of pandemics and we must learn from our observations at present with SARS-CoV-2 infection, and resulting COVID-19 disease. Virus isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for diagnostic and research purposes Rapid deployment of pathology services to a remote Australian quarantine setting during the COVID-19 pandemic abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33121820/ doi: 10.1016/j.pathol.2020.09.010 id: cord-350737-nrtrhq1f author: Chen, Xinchun title: Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome date: 2004-04-01 words: 3474.0 sentences: 133.0 pages: flesch: 50.0 cache: ./cache/cord-350737-nrtrhq1f.txt txt: ./txt/cord-350737-nrtrhq1f.txt summary: A virus from the family Coronaviridae, termed "SARS coronavirus" (SARS CoV), has been identified as the cause [2] [3] [4] [5] [6] [7] , and criteria for laboratory confirmation of SARS CoV infection have been provided by WHO, on the basis of the following methods: (1) detection of SARS CoV RNA by reversetranscription polymerase chain reaction (RT-PCR); (2) serological detection of SARS CoV-related antibody; and (3) isolation of SARS CoV by cell culture [4] . Using an indirect immunofluorescence assay and parallel acute and convalescent serum samples obtained from patients with SARS, tested for IgG antibody to SARS CoV, Peiris et al. In addition, our results indicated that 9 (25.0%) of 36 patients with probable SARS CoV infection had not produced detectable anti-SARS CoV antibody by day 21 after the onset of fever; this implies that 25.0% of patients with SARS might be misdiagnosed by the laboratory confirmation guidelines that WHO currently recommends [5] . abstract: Background. Severe acute respiratory syndrome (SARS) is a novel infectious disease. No information is currently available on host-specific immunity against the SARS coronavirus (CoV), and detailed characteristics of the epidemiology of SARS CoV infection have not been identified. Methods. ELISA was used to detect antibody to SARS CoV. Reverse-transcriptase polymerase chain reaction was used to detect SARS CoV RNA. T cells in peripheral blood of patients were quantified by flow cytometry. Results. Of 36 patients with probable SARS CoV infection, 30 (83.3%) were positive for IgG antibody to SARS CoV; in contrast, only 3 of 48 patients with suspected SARS CoV infection, 0 of 112 patients with fever but without SARS, and 0 of 96 healthy control individuals were positive for it. IgG antibody to SARS CoV was first detected between day 5 and day 47 after onset of illness (mean ± SD, 18.7±10.4). Conclusion. Detection of antibody to SARS CoV is useful in the diagnosis of SARS; however, at the incubation and initial phases of the illness, serological assay is of little value, because of late seroconversion in most patients. url: https://www.ncbi.nlm.nih.gov/pubmed/15031782/ doi: 10.1086/380397 id: cord-350015-mg5wiihj author: Chen, Yiyin title: Aging in COVID-19: Vulnerability, immunity and intervention date: 2020-10-31 words: 7489.0 sentences: 407.0 pages: flesch: 47.0 cache: ./cache/cord-350015-mg5wiihj.txt txt: ./txt/cord-350015-mg5wiihj.txt summary: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and has caused a profound and yet still unfolding health and socioeconomic impacts. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Therefore, age-associated reduction in type 1 IFN response coupled with direct viral suppression could serve as a critical innate immune mechanism that leads to poor cell mediated immunity and increased vulnerability of older adults against SARS-CoV-2 infection with therapeutic implication (Sallard et al., 2020) . On the other hand, children with COVID-19 manifested lower levels of T cell activation than adult COVID-19 patients (Moratto et al., 2020) , suggesting better immune system control and regulation in response to SARS-CoV-2 infection in children. abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic was first reported in Wuhan, China in December 2019, moved across the globe at an unprecedented speed, and has caused a profound and yet still unfolding health and socioeconomic impacts. SARS-CoV-2, a β-coronavirus, is a highly contagious respiratory pathogen that causes a disease that has been termed the 2019 coronavirus disease (COVID-19). Clinical experience thus far indicates that COVID-19 is highly heterogeneous, ranging from being asymptomatic and mild to severe and causing death. Host factors including age, sex, and comorbid conditions are key determinants of disease severity and progression. Aging itself is a prominent risk factor for severe disease and death from COVID-19. We hypothesize that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults. Much remains to be learned about the immune responses to SARS-CoV-2 infection. We need to begin partitioning all immunological outcome data by age to better understand disease heterogeneity and aging. Such knowledge is critical not only for understanding of COVID-19 pathogenesis but also for COVID-19 vaccine development. url: https://doi.org/10.1016/j.arr.2020.101205 doi: 10.1016/j.arr.2020.101205 id: cord-311762-f6muhf3d author: Chen, Yu Wai title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates date: 2020-02-21 words: 2798.0 sentences: 183.0 pages: flesch: 60.0 cache: ./cache/cord-311762-f6muhf3d.txt txt: ./txt/cord-311762-f6muhf3d.txt summary: title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates Therefore, we are confident to prepare a structural model of the SARS-CoV-2 3CL pro by molecular modelling (Extended data 7 , Figure S1 ), which will be immediately useful for in silico development of targeted treatment. After we submitted the first draft of this study, the crystal structure of SARS-CoV-2 3CL pro was solved and released (PDB ID 6LU7), which confirms that the predicted model is good within experimental errors (Extended data 7 , Figure S2 ). By analogy, these compounds were speculated to act on SARS-CoV 3CL pro specifically, but there is as yet no crystal structure to support that, although docking studies were carried out to propose various binding modes 20-23 . • Tab S2.docx (The results of virtual screening of drugs on the active site of SARS-CoV-2 3CL pro crystal structure). abstract: We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL (pro)) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL (pro) molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes. url: https://doi.org/10.12688/f1000research.22457.1 doi: 10.12688/f1000research.22457.1 id: cord-275946-ofd2ipvs author: Cheng, Matthew P. title: Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review date: 2020-06-04 words: 5277.0 sentences: 282.0 pages: flesch: 38.0 cache: ./cache/cord-275946-ofd2ipvs.txt txt: ./txt/cord-275946-ofd2ipvs.txt summary: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. Appropriately designed seroepidemiologic studies will play an essential part in the public health response to the COVID-19 pandemic by characterizing transmission dynamics, refining disease burden estimates, and providing insight into the kinetics of humoral immunity to SARS-CoV-2. Serologic surveillance studies can also assess the accumulation of persons with antibody responses over time to estimate incidence of SARS-CoV-2 infection (57, 58) and can track age-and jurisdiction-specific disease susceptibility and identify at-risk populations (59) . abstract: Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. url: https://doi.org/10.7326/m20-2854 doi: 10.7326/m20-2854 id: cord-282338-u01qv3uc author: Cherry, James. D. title: The chronology of the 2002–2003 SARS mini pandemic date: 2004-11-05 words: 3528.0 sentences: 176.0 pages: flesch: 55.0 cache: ./cache/cord-282338-u01qv3uc.txt txt: ./txt/cord-282338-u01qv3uc.txt summary: SARS-CoV disease should be considered at a minimum in the differential diagnoses for persons requiring hospitalisation for pneumonia confirmed radiographically or acute respiratory distress syndrome without identifiable aetiology and who have one of the following risk factors in the 10 days before the onset of illness: (1) Travel to mainland China, Hong Kong, or Taiwan, or close contact with an ill person with a history of recent travel to one of these areas, or; (2) Employment in an occupation associated with a risk for SARS-CoV exposure (e.g. healthcare worker with direct patient contact or worker in a laboratory that contains live SARS-CoV) or; (3) Part of a cluster of cases of atypical pneumonia without an alternative diagnosis. abstract: Severe acute respiratory syndrome (SARS) was a new human disease in the autumn of 2002. It first occurred in Southern China in November 2002 and was transported to Hong Kong on February 21, 2003 by an infected and ill patient. Ten secondary cases spread the infection to two hospitals in Hong Kong and to Singapore, Toronto and Hanoi. In March 2003 a novel coronavirus (SARS-CoV) was found to be the causative agent. Within 11 weeks from the first SARS case in Hong Kong it had spread to an additional 27 countries or special administrative regions. The mini pandemic peaked during the last week of May 2003 and the last new probable case was on July 13, 2003. There were a total of 8096 probable cases and 774 deaths. Sixty-six per cent of the cases occurred in China, 22% in Hong Kong, 4% in Taiwan and 3% in both Singapore and Canada. Twenty-one per cent of all cases occurred in healthcare workers. url: https://www.sciencedirect.com/science/article/pii/S1526054204000788 doi: 10.1016/j.prrv.2004.07.009 id: cord-327654-9g8zcxaa author: Chi, Xiaojing title: Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain date: 2020-09-10 words: 4993.0 sentences: 302.0 pages: flesch: 51.0 cache: ./cache/cord-327654-9g8zcxaa.txt txt: ./txt/cord-327654-9g8zcxaa.txt summary: Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. To determine whether sdAbs targeted different antigenic regions on the SARS-CoV-2 RBD surface, we performed a competition-binding assay using a real-time biosensor (Fig. 3) . Fc fusion sdAbs in culture supernatants were affinity purified with HiTrap Protein A HP antibody purification columns ( Supplementary Fig. 2 ) and analyzed in both reducing and non-reducing conditions in Western blot using an anti-human IgG to detect Fc. As shown in Fig. 4c , the size of the constructed intact sdAb-Fc is around 80 KDa in the non-reducing condition, but a 40 KDa monomer was observed by prior treatment in reducing condition to break disulfide bonds. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant (K(D)) of 0.99–35.5 nM. The monomeric sdAbs show half maximal neutralization concentration (EC(50)) of 0.0009–0.07 µg/mL and 0.13–0.51 µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies. url: https://doi.org/10.1038/s41467-020-18387-8 doi: 10.1038/s41467-020-18387-8 id: cord-274141-vujx538o author: Chinsembu, Kazhila C. title: Coronaviruses and Nature’s Pharmacy for the Relief of Coronavirus Disease 2019 date: 2020-10-06 words: 11338.0 sentences: 676.0 pages: flesch: 53.0 cache: ./cache/cord-274141-vujx538o.txt txt: ./txt/cord-274141-vujx538o.txt summary: De Clercq (2005 suggested that it was feasible to develop SARS-CoV fusion inhibitors analogous to enfuvirtide, a linear 36-amino acid synthetic peptide marketed under the trade name Fuzeon, an approved anti-HIV drug that inhibits the entry of the virus into cells. It was hypothesized that specific flavonoids, such as quercetin, hesperetin, and myricetin (7) and their glycosylated derivatives, may play an effective role in inhibiting SARS-CoV entry into host cells, specifically by binding with high affinity to the spike protein, helicase, and protease sites on the ACE receptor (Ngwa et al. Although the ongoing SARS-CoV-2 global pandemic should remind scientists that current options for treating life-threatening zoonotic coronavirus infections are very limited , medicinal plants offer a strong pipeline for the discovery of novel lead compounds that can be converted into new drugs to treat COVID-19. abstract: [Image: see text] url: https://doi.org/10.1007/s43450-020-00104-7 doi: 10.1007/s43450-020-00104-7 id: cord-333498-d25qfq0f author: Chitranshi, Nitin title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates date: 2020-07-09 words: 5999.0 sentences: 378.0 pages: flesch: 51.0 cache: ./cache/cord-333498-d25qfq0f.txt txt: ./txt/cord-333498-d25qfq0f.txt summary: Recent release of the high-resolution crystal structure for the main proteinase 3CL pro (Protein Data Bank, PDB ID: 6Y2G), describing an additional amide bond with the α-ketoamide inhibitor pyridone ring to enhance the half-life of the compound in plasma [16] is suggested to accelerate the targeted drug discovery efforts. Since the initial stages of the SARS-CoV-2 outbreak, laboratories and hospitals around the world have sequenced viral genome data with unprecedented speed, enabling real-time understanding of this novel disease process, which will hopefully contribute to the development of novel candidate drugs. In contrast, our docking studies revealed that bilobetin, predicted almost comparable binding energy with that of amentaflavone (− 8.29 kcal/mol) suggesting that mutation in SARS-CoV-2 3CL pro could potentially disrupt hydrogen bonding or induce some conformational change that could result in alterations in the binding site thus affecting inhibitor interactions with the enzyme active site residues. abstract: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL(pro)) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL(pro) enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic. url: https://doi.org/10.1186/s12967-020-02448-z doi: 10.1186/s12967-020-02448-z id: cord-337812-arivkkj0 author: Chu, Ling-Hon Matthew title: Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry date: 2006-03-07 words: 6860.0 sentences: 286.0 pages: flesch: 52.0 cache: ./cache/cord-337812-arivkkj0.txt txt: ./txt/cord-337812-arivkkj0.txt summary: To screen the substrate specificity of SARS-CoV 3CL pro in a rapid and highthroughput manner in contrast to the traditional tedious procedures, we applied the matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOF MS) analysis in combination with the novel "cartridge replacement" solid-phase peptide synthesis approach to investigate the biological significance of amino acid residues in the P2, P3, P4, P1¢, P2¢, and P3¢ positions that are flanking the conserved Gln residue in the P1 position at the SARS-CoV 3CL pro cleavage site (Schechter and Berger 1967; Fan et al. In this study, we used MALDI-TOF MS analysis in combination with the solid-phase peptide synthesis approach to examine the biological significance of amino acid residues in a total of six target positions at the SARS-CoV 3CL pro cleavage sites, including the P2, P3, and P4 positions at the amino side of the P1 position; and the P1¢, P2¢, and P3¢ positions at the carboxyl side of the P1 position (Table 1) . abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CL(pro)) mediates extensive proteolytic processing of replicase polyproteins, and is considered a promising target for anti-SARS drug development. Here we present a rapid and high-throughput screening method to study the substrate specificity of SARS-CoV 3CL(pro). Six target amino acid positions flanking the SARS-CoV 3CL(pro) cleavage site were investigated. Each batch of mixed peptide substrates with defined amino acid substitutions at the target amino acid position was synthesized via the “cartridge replacement” approach and was subjected to enzymatic cleavage by recombinant SARS-CoV 3CL(pro). Susceptibility of each peptide substrate to SARS-CoV 3CL(pro) cleavage was monitored simultaneously by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The hydrophobic pocket in the P2 position at the protease cleavage site is crucial to SARS-CoV 3CL(pro)-specific binding, which is limited to substitution by hydrophobic residue. The binding interface of SARS-CoV 3CL(pro) that is facing the P1′ position is suggested to be occupied by acidic amino acids, thus the P1′ position is intolerant to acidic residue substitution, owing to electrostatic repulsion. Steric hindrance caused by some bulky or β-branching amino acids in P3 and P2′ positions may also hinder the binding of SARS-CoV 3CL(pro). This study generates a comprehensive overview of SARS-CoV 3CL(pro) substrate specificity, which serves as the design basis of synthetic peptide-based SARS-CoV 3CL(pro) inhibitors. Our experimental approach is believed to be widely applicable for investigating the substrate specificity of other proteases in a rapid and high-throughput manner that is compatible for future automated analysis. url: https://www.ncbi.nlm.nih.gov/pubmed/16600962/ doi: 10.1110/ps.052007306 id: cord-322913-sq9mq6f1 author: Ciabattini, Annalisa title: Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population date: 2020-11-06 words: 8068.0 sentences: 363.0 pages: flesch: 33.0 cache: ./cache/cord-322913-sq9mq6f1.txt txt: ./txt/cord-322913-sq9mq6f1.txt summary: The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of innate and adaptive immune responses, and the lack of a clear correlate of protection, make the design of vaccination strategies for older people extremely challenging (Fig. 3 ). abstract: The SARS-CoV-2 pandemic urgently calls for the development of effective preventive tools. COVID-19 hits greatly the elder and more fragile fraction of the population boosting the evergreen issue of the vaccination of older people. The development of a vaccine against SARS-CoV-2 tailored for the elderly population faces the challenge of the poor immune responsiveness of the older population due to immunosenescence, comorbidities, and pharmacological treatments. Moreover, it is likely that the inflammaging phenotype associated with age could both influence vaccination efficacy and exacerbate the risk of COVID-19-related “cytokine storm syndrome” with an overlap between the factors which impact vaccination effectiveness and those that boost virulence and worsen the prognosis of SARS-CoV-2 infection. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. In the ongoing effort in vaccine development, different SARS-CoV-2 vaccine candidates have been developed, tested in pre-clinical and clinical studies and are undergoing clinical testing, but only a small fraction of these are currently being tested in the older fraction of the population. Recent advances in systems biology integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly. url: https://doi.org/10.1007/s00281-020-00821-0 doi: 10.1007/s00281-020-00821-0 id: cord-340305-jtvn9tlm author: Cimolai, Nevio title: A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19 date: 2020-09-19 words: 5105.0 sentences: 294.0 pages: flesch: 40.0 cache: ./cache/cord-340305-jtvn9tlm.txt txt: ./txt/cord-340305-jtvn9tlm.txt summary: At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Others have found strong correlations between neutralizing antibodies and EIA-detected antibodies to various SARS-CoV-2 antigens [41, 42] .Some have found diversity in immune responses contingent on the nature of presenting disease [38, 43] . With the availability of viral antigen, most scientists in the know-how would be able to fashion a test for antibody determination in short order and most would likely choose an enzyme immunoassay (EIA) (or nearly equivalent non-enzymebased assay) for its potential of automation and widespread use. Sensitive and specific detection of low-level antibody responses in mild Middle East Respiratory Syndrome coronavirus infections A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients abstract: Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy. url: https://doi.org/10.1007/s42399-020-00533-4 doi: 10.1007/s42399-020-00533-4 id: cord-275454-an8xvow3 author: Clark, Andrew E title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Screening With Specimen Pools: Time to Swim, or Too Deep for Comfort? date: 2020-09-28 words: 1607.0 sentences: 87.0 pages: flesch: 48.0 cache: ./cache/cord-275454-an8xvow3.txt txt: ./txt/cord-275454-an8xvow3.txt summary: We read with interest the study appearing in this issue by Li et al, who utilized a pooled sample strategy and a point-of-care (POC) reverse transcriptase-polymerase chain reaction (RT-PCR) assay for screening asymptomatic airline passengers arriving from areas of high SARS-CoV-2 prevalence. At the time of this writing, 2 reference laboratories in the United States (Quest Diagnostics and LabCorp) have received emergency use authorizations from the US Food and Drug Administration to use pooled specimens for SARS-CoV-2 detection [2] . In this work, pooling was performed in a 10:1 ratio, meaning 10 patient specimens were combined and tested using a single SARS-CoV-2 assay. At our institution, we are aware of patients who underwent preprocedure SARS-CoV2 screening utilizing the same assay deployed in this work, only to be diagnosed with active, symptomatic COVID-19 within 5 days of testing. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32986122/ doi: 10.1093/cid/ciaa1145 id: cord-341453-9yrvjlpx author: Clay, Candice C title: Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses date: 2014-03-19 words: 8130.0 sentences: 395.0 pages: flesch: 48.0 cache: ./cache/cord-341453-9yrvjlpx.txt txt: ./txt/cord-341453-9yrvjlpx.txt summary: The aim of this study was to determine how the peripheral and mucosal immune responses to SARS-CoV infection compare in the aged and juvenile nonhuman primate host and to determine how this may impact viral replication levels. No virus was detected in any sample collected from either age group at 10 d.p.i. To determine if advanced age correlated with increased severity of lung pathology, a comprehensive histological analysis of the respiratory tract following SARS-CoV infection was conducted in aged and juvenile animals. To determine how mucosal cytokines in SARS-CoV infection compared to systemic responses and how age may impact mucosal cytokine expression; the inflammatory protein profile was evaluated by bead-based arrays in standardized-collected lung tissue from the proximal portion of the right caudal lobe. Although no age-dependent differences were observed in the frequency of naïve (CD45RA + CCR7+) CD8 T cells in peripheral blood, there were significantly lower levels of these cells in the lung and lymph node of aged animals during SARS-CoV infection ( Figure 6A -C; unpaired student T-tests). abstract: BACKGROUND: Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure. RESULTS: Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age. CONCLUSIONS: This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates. url: https://doi.org/10.1186/1742-4933-11-4 doi: 10.1186/1742-4933-11-4 id: cord-031289-uxoz0xhk author: Coccolini, Federico title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients date: 2020-05-18 words: 1326.0 sentences: 98.0 pages: flesch: 51.0 cache: ./cache/cord-031289-uxoz0xhk.txt txt: ./txt/cord-031289-uxoz0xhk.txt summary: title: SARS-CoV-2 Is Present in Peritoneal Fluid in COVID-19 Patients The present article represents the very first positive result describing the presence of the virus in peritoneal fluid during an emergency surgical procedure in a COVID-19 sick patient. Interestingly, the nasal swab contained less SARS-CoV-2 RNA virus compared to the viral fluid that scored positive in 2 targets out of 3. This indicates that the viral load in the peritoneal fluid was higher compared to the upper respiratory material and suggests that the surgical operation was indeed a procedure at risk of infection. As no information exist about the virus passage to peritoneal cavity and fluids, present data may suggest that potentially all people even those with mild to moderate respiratory symptoms by SARS-CoV-2 could present viral load in peritoneal fluid, thus increasing the exposure and contagion risks for the entire surgical staff.Peritoneal fluid contamination with blood of feces may interfere with the virus detection. abstract: BACKGROUND: The excretion pathomechanisms of SARS-CoV-2 are actually unknown. No certain data exist about viral load in the different body compartments and fluids during the different disease phases. MATERIAL AND METHODS: Specific real-time reverse transcriptase–polymerase chain reaction targeting 3 SARS-CoV-e genes were used to detect the presence of the virus. RESULTS: SARS-CoV-2 was detected in peritoneal fluid at a higher concentration than in respiratory tract. CONCLUSION: Detection of SARS-CoV-2 in peritoneal fluid has never been reported. The present article represents the very first positive result describing the presence of the virus in peritoneal fluid during an emergency surgical procedure in a COVID-19 sick patient. This article thus represents a warning for increasing the level of awareness and protection for surgeon especially in emergency surgical setting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467036/ doi: 10.1097/sla.0000000000004030 id: cord-328000-i9tzr13z author: Cockrell, Adam S. title: Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice date: 2018-07-24 words: 11004.0 sentences: 519.0 pages: flesch: 44.0 cache: ./cache/cord-328000-i9tzr13z.txt txt: ./txt/cord-328000-i9tzr13z.txt summary: Three different strategies were employed for development of SARS-CoV mouse models: (i) different mouse species (or subspecies) were challenged with wildtype human SARS-CoV isolates in order to find a model that allows for replication and reflects severe respiratory disease symptoms observed in infected human patients; (ii) mice were genetically engineered to modify the host receptor, which facilitated productive SARS-CoV replication and pathogenesis; and (iii) adaptive evolution of wild-type SARS-CoV to a chosen mouse species was done to enhance pathogenesis, and associated clinical phenotypes in vivo. To adapt SARS-CoV to cause severe acute respiratory disease in mouse lungs, 6-week-old female BALB/c mice were intra-nasally infected with the clinical Urbani isolate (Roberts et al. Virus infection studies in CC mouse lines, including SARS-CoV, have led to mapping of high and low host response alleles as they relate to development of clinical signs of disease following viral pathogenesis (Bottomly et al. abstract: The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV–host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV–host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus–host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV–host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions. url: https://doi.org/10.1007/s00335-018-9760-9 doi: 10.1007/s00335-018-9760-9 id: cord-279940-i2rgjpxf author: Comentale, Giuseppe title: Sars-Cov-2 interference in HEME production: is it the time for an early predictive biomarker? date: 2020-06-29 words: 1348.0 sentences: 65.0 pages: flesch: 43.0 cache: ./cache/cord-279940-i2rgjpxf.txt txt: ./txt/cord-279940-i2rgjpxf.txt summary: In particular, thrombosis seems to drive the entire disease course: Sars-Cov-2 infection triggers a large thrombophilic response that results in diffuse occlusion of the smaller vessels, especially in the lungs where the result is a wide thrombotic microangiopathy [5] explaining the radiologic "ground glass" pattern. Furthermore, as IL-1 was shown to be a major culprit in the development of many cardiovascular diseases [11] , its involvement in the Sars-Cov-2 infection could explain the high mortality and morbidity rate among cardiopathic patients. Identifying the mechanisms by which Sars-Cov-2 damages the human body, focusing on the structural proteins, could be a possible strategy to finding an effective solution. From this point of view, Sars-Cov-2 seems to be very similar to malaria: many clinical and scientific reports have shown that Covid-19, not only can be successfully treated with chloroquine but also, like malaria, appears to be diagnosed much more frequently in blood group A patients [14] . abstract: nan url: https://doi.org/10.1007/s00109-020-01945-4 doi: 10.1007/s00109-020-01945-4 id: cord-311125-v9ddes3c author: Cooper, Keiland W. title: COVID-19 and the chemical senses: supporting players take center stage date: 2020-07-01 words: 9480.0 sentences: 510.0 pages: flesch: 49.0 cache: ./cache/cord-311125-v9ddes3c.txt txt: ./txt/cord-311125-v9ddes3c.txt summary: Given data suggesting that ACE2 is necessary for SARS-CoV2 to infect host cells, researchers have used a variety of approaches to discern the pattern of expression of ACE2 and other viral entry proteins across the tissue landscape, with the goal of inferring possible target cells and disease mechanisms. It remains unclear whether SARS-CoV-2 (given that it likely does not directly infect OSNs, and thus cannot pass directly through the olfactory nerve, see However, scSeq and immunostaining of the mouse OB has revealed -as in the nose -that bulb neurons do not express detectable levels of ACE2 ( Figure 2 ) . This model suggests that neural function is altered indirectly due to sequelae of SARS-CoV-2 infection of peripheral support cells, including (but not limited to) local inflammation and changes in OSN gene expression and ciliary structure. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia abstract: Abstract The main neurological manifestation of COVID-19 is loss of smell or taste. The high incidence of smell loss without significant rhinorrhea or nasal congestion suggests that SARS-CoV-2 targets the chemical senses through mechanisms distinct from those used by endemic coronaviruses or other common cold-causing agents. Here we review recently developed hypotheses about how SARS-CoV-2 might alter the cells and circuits involved in chemosensory processing and thereby change perception. Given our limited understanding of SARS-CoV-2 pathogenesis, we propose future experiments to elucidate disease mechanisms and highlight the relevance of this ongoing work to understanding how the virus might alter brain function more broadly. url: https://doi.org/10.1016/j.neuron.2020.06.032 doi: 10.1016/j.neuron.2020.06.032 id: cord-312670-hi3fjne4 author: Corman, V. M. title: Coronaviren als Ursache respiratorischer Infektionen date: 2019-08-27 words: 2307.0 sentences: 257.0 pages: flesch: 49.0 cache: ./cache/cord-312670-hi3fjne4.txt txt: ./txt/cord-312670-hi3fjne4.txt summary: Zusätzlich zu diesen ständig im Menschen zirkulierenden Varianten wurden in den vergangenen Jahren zwei CoV im Menschen gefunden, nämlich SARS-CoV und MERS-CoV, die aus dem Tierreservoir auf den Menschen übergegangen sind und bei einem deutlich größeren Anteil der Infizierten schwere virale Pneumonien mit tödlichem Verlauf auslösen [25, 28] . Obwohl die Mehrzahl der Infektionen mit den vier endemischen CoV nur leichte Atemwegserkrankungen verursacht, können alle HCoV auch schwere Hier steht eine Anzeige. Inwiefern diese sekundären Infektionen auf die intensivmedizinische Behandlung und Beatmung zurückzuführen sind oder ein spezifisches grundsätzliches Risiko einer CoV-Infektion darstellen, ist noch nicht verstanden. Jedoch ist eine spezifische Labordiagnostik bei Verdacht auf eine Infektion mit endemi-schen CoV bei harmlosem Verlauf und Patienten ohne besonderes Risiko für die Entstehung von Komplikationen auch nicht indiziert. Bei der typischerweise unspezifischen Klinik von MERS-CoV-Infektionen sollte auch die Möglichkeit einer Infektion mit anderen Pathogenen in Betracht gezogen werden [26] . RKI (2015) Schwere respiratorische Erkrankungen in Verbindung mit Middle East Respiratory Syndrome Coronavirus (MERS-CoV). abstract: BACKGROUND: There are six human pathogenic coronaviruses (CoV), which mainly cause infections of the respiratory system. In everyday clinical practice, it is helpful to know the relevance and characteristics of these pathogens. OBJECTIVE: To present the epidemiology, clinical picture and differences of human pathogenic CoV and to provide information on the diagnostics and treatment of patients suspected of having CoV infections. MATERIAL AND METHODS: Selective literature search, presentation of results and discussion of fundamental works and expert recommendations, including publications by the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC) and the Robert Koch Institute. RESULTS: The four endemic human CoVs (HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1) mainly cause mild respiratory tract infections. In addition to these four endemic HCoV, the two epidemic CoV, severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV can cause severe pneumonia. The SARS-CoV has not been detected in humans in the last 15 years and MERS-CoV has been circulating mainly on the Arabian Peninsula since 2012; however, neither a specific treatment nor approved vaccines exist for any of the six human pathogenic CoVs. CONCLUSION: All six human CoVs can be diagnosed using RT-PCR on respiratory specimens but this is rarely necessary for the four endemic strains. In current clinical practice SARS-CoV has no importance as it has not been detected in humans for 15 years; however, a possible MERS-CoV infection should be taken into account in patients with typical symptoms and travel history to endemic regions. In this case, rapid diagnostic and general hygiene practices are important to prevent further transmission. url: https://doi.org/10.1007/s00108-019-00671-5 doi: 10.1007/s00108-019-00671-5 id: cord-332723-rz1iilsv author: Creager, Hannah M. title: Clinical evaluation of the BioFire® Respiratory Panel 2.1 and detection of SARS-CoV-2 date: 2020-07-06 words: 1474.0 sentences: 114.0 pages: flesch: 60.0 cache: ./cache/cord-332723-rz1iilsv.txt txt: ./txt/cord-332723-rz1iilsv.txt summary: Since 30% of nasopharyngeal swab specimens have a SARS CoV-2 Ct >30 and thus detection of virus in low titers is clinically relevant, a sample with a high titer was diluted and each 10 fold dilution was tested in triplicate and compared against 6 other EUA approved SARS CoV-2 assays. These data suggested that the BioFire® RP2.1 panel, along with four other SARS CoV-2 assays (Roche cobas, Cepheid Xpert Xpress, BioFire® Defense COVID19, and NECoV19), consistently detected viral RNA at the 10-7 dilution. Ten-fold serial dilutions of a natural nasopharyngeal swab specimen with known high positivity for SARS-CoV-2 RNA (E gene detected at a cycle threshold (Ct) of 16.6 by the cobas SARS-CoV-2 assay) were prepared with a diluent of pooled NPS. Comparison of SARS-CoV-2 Detection from Nasopharyngeal Swab Samples by the Roche cobas(R) 6800 SARS-CoV-2 Test and a Laboratory-Developed Real-Time RT-PCR test abstract: We evaluated the performance of the BioFire® Respiratory Panel 2.1 (RP2.1) in the detection of SARS CoV-2 in comparison against three other SARS CoV-2 EUA assays. In these studies, the RP2.1 panel had 98% positive percent agreement (48/49) and 100% negative percent agreement (49/49). Since 30% of nasopharyngeal swab specimens have a SARS CoV-2 Ct >30 and thus detection of virus in low titers is clinically relevant, a sample with a high titer was diluted and each 10 fold dilution was tested in triplicate and compared against 6 other EUA approved SARS CoV-2 assays. These data suggested that the BioFire® RP2.1 panel, along with four other SARS CoV-2 assays (Roche cobas, Cepheid Xpert Xpress, BioFire® Defense COVID19, and NECoV19), consistently detected viral RNA at the 10-7 dilution. Overall, these studies suggest that the BioFire® RP2.1 assay can be used to detect acute cases of SARS CoV2 in addition to patients with low viral titer later in disease presentation. url: https://doi.org/10.1016/j.jcv.2020.104538 doi: 10.1016/j.jcv.2020.104538 id: cord-344266-ug2uew71 author: Crema, E. title: The SARS-COV-2 outbreak around the Amazon rainforest: the relevance of the airborne transmission date: 2020-08-07 words: 3951.0 sentences: 215.0 pages: flesch: 54.0 cache: ./cache/cord-344266-ug2uew71.txt txt: ./txt/cord-344266-ug2uew71.txt summary: Currently, this phenomenon has gained tragic relevance due to the uncontrolled dispersion of the Covid-19 throughout the planet, since airborne transmission is one of the forms of viral contamination, as well as the direct reception of drops exhaled by a contaminated person and the contact with infected surfaces. A relevant study issued in the journal Nature revealed the existence of the RNA of the SARS-COV-2 in aerosols collected from the air of several closed environments and open places of two hospitals in Wuhan dedicated only to patients infected with Covid-19 (12) . This indication is based only on old studies about the direct transmission by larger drops, dangerously ignoring the contamination by the virus airborne in droplets that remain suspended in the air for several hours, and even days after the environment has been visited by an infected person. abstract: Background This paper presents a global analysis of the SARS-COV-2 outbreak in Brazil. Amazonian States have a much higher contamination rate than the southern and southeastern States. So far, no explanation has been provided for this striking difference that can shed light on the airborne transmission of the virus. Minimizing airborne transmission, health authorities recommend two meters as a safe distance. However, recent experiments reveal that this can be the main form of contagion. There is a lack of theoretical explanation on how airborne transmission works. Methods To investigate the spread of SARS-COV-2 in different macro environments, we analyzed the daily official data on the evolution of COVID-19 in Brazil. We compared our epidemiologic results obtained in States with very different climatic characteristics, and that had adopted, almost simultaneously, similar social isolation measures. To understand the virus spread, it was necessary to calculate theoretically the movement and behavior in the air of saliva droplets. Findings The transmission of SARS-COV-2 is much faster in the Amazon rainforest region. Our theoretical calculations explain and support the empirical results observed in recent experiments that demonstrate the relevance of aerial transmission of the coronavirus. Interpretation An onset of collective immunity may have been achieved with a contamination rate of about 15% of the Amazonian population. If confirmed, this result will have an essential impact on the management of the pandemic across the planet. The airborne transmission played a decisive role in the striking difference in the evolution of the pandemic among Brazilian regions. Air humidity is the most important climatic factor in viral spreading, while usual ambient temperatures do not have strong influence. There is no safe indoor distance for the coronavirus transmission. So, mask and eye protection are essential. url: http://medrxiv.org/cgi/content/short/2020.08.06.20169433v1?rss=1 doi: 10.1101/2020.08.06.20169433 id: cord-322957-clf8f90t author: Crespo, Javier title: Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG date: 2020-04-28 words: 5297.0 sentences: 364.0 pages: flesch: 51.0 cache: ./cache/cord-322957-clf8f90t.txt txt: ./txt/cord-322957-clf8f90t.txt summary: The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. abstract: Abstract The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. • To protect all healthcare professionals against the risks of infection with SARS-CoV-2. • To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2. url: https://api.elsevier.com/content/article/pii/S2444382420300717 doi: 10.1016/j.gastre.2020.04.001 id: cord-352123-0bflqj1c author: Csiszar, Anna title: Companion animals likely do not spread COVID-19 but may get infected themselves date: 2020-08-07 words: 4752.0 sentences: 225.0 pages: flesch: 51.0 cache: ./cache/cord-352123-0bflqj1c.txt txt: ./txt/cord-352123-0bflqj1c.txt summary: Recent evidence suggests that SARS-CoV-2, similar to other coronaviruses, can infect several species of animals, including companion animals such as dogs, cats, and ferrets although their viral loads remain low. In late March 2020, the Federal Agency for the Safety of the Food Chain (FASFC) in Belgium reported that a pet cat was diagnosed to be infected with SARS-CoV-2 [21, 22] , showing that felines living in the household of people with COVID-19 are at risk of contracting the disease and may potentially spread the virus. On April 23, it was reported that two pet cats in New York state have tested positive for the SARS-CoV-2, which are the first confirmed COVID-19 cases in companion animals in the USA [22] . In the current SARS-CoV-2 pandemic, the situation is rapidly evolving and in the light of the recent evidence, we should be aware of the possibility that humans can be potentially infected with COVID-19 by animals, including by pet cats, dogs, or other domesticated species. abstract: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From the epidemiological data, the picture emerges that the more severe etiopathologies among COVID-19 patients are found in elderly people. The risk of death due to COVID-19 increases exponentially with age. Eight out of 10 COVID-19 related deaths occur in people older than 65 years of age. Older patients with comorbid conditions such as hypertension, heart failure, diabetes mellitus, asthma, chronic obstructive pulmonary disease, and cancer have a much higher case fatality rate. Governments and public health authorities all over the world have realized that protections of vulnerable older adults should be a priority during the COVID-19 pandemic. COVID-19 is a zoonotic disease. The SARS-CoV-2 virus was originally transmitted likely from a bat or a pangolin to humans. Recent evidence suggests that SARS-CoV-2, similar to other coronaviruses, can infect several species of animals, including companion animals such as dogs, cats, and ferrets although their viral loads remain low. While the main source of infection transmission therefore is human to human, there are a few rare cases of pets contracting the infection from a SARS-CoV-2-infected human. Although there is no evidence that pets actively transmit SARS-CoV-2 via animal-to-human transmission, senior pet ownership potentially may pose a small risk to older adults by (1) potentially enabling animal-to-human transmission of SARS-CoV-2 in the most vulnerable population and (2) by increasing the exposition risk for the elderly due to the necessity to care for the pet and, in the case of dogs, to take them outside the house several times per day. In this overview, the available evidence on SARS-CoV-2 infection in pets is considered and the potential for spread of COVID-19 from companion animals to older individuals and the importance of prevention are discussed. url: https://doi.org/10.1007/s11357-020-00248-3 doi: 10.1007/s11357-020-00248-3 id: cord-314171-431buxxr author: Dariya, Begum title: Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients date: 2020-05-06 words: 6892.0 sentences: 421.0 pages: flesch: 51.0 cache: ./cache/cord-314171-431buxxr.txt txt: ./txt/cord-314171-431buxxr.txt summary: In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. The mRNA and protein ACE2 expression levels are higher in these patients with cardiac disease, creating an increased risk for severe COVID-19 complications, including heart failure. After SARS-CoV-2 binds with ACE2, the virus degrades it, and thus the free angiotensin II induces acute lung injury [58] . Thus, targeting the binding site of the ACE2 receptor and SARS-CoV-2 with antibodies or therapeutic drugs might provide a successful treatment strategy. Moreover, this also increases the level of soluble ACE2 that competitively binds with SARS-CoV-2, causing delayed entry of the virus into cells and protecting against lung injury. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2 abstract: The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future. url: https://doi.org/10.1016/j.cytogfr.2020.05.001 doi: 10.1016/j.cytogfr.2020.05.001 id: cord-303216-1pbuywz6 author: Das, Gaurav title: Neurological Insights of COVID-19 Pandemic date: 2020-04-22 words: 2872.0 sentences: 155.0 pages: flesch: 54.0 cache: ./cache/cord-303216-1pbuywz6.txt txt: ./txt/cord-303216-1pbuywz6.txt summary: If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. The intriguing part though is that recently reported studies have noted altered mental health in some COVID-19 patients showing symptoms like anosmia and ageusia thereby indicating a neuroinvasive nature of the virus. The neurological manifestations of SARS-CoV-2 have been recently recognized from CT scan images and MRI scan of the brain of a patient who contracted COVID-19 and showed symptoms of necrotizing hemorrhagic encephalopathy. The brain reportedly, like most other organs, expresses the hACE2 considered to be the entry point of the SARS-CoV-2 viruses in humans and is therefore not immune to viral infection. abstract: The novel coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The virus is unlike its previous counterparts, SARS-CoV and MERS-CoV, or anything the world has encountered before both in terms of virulence and severity of the infection. If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. Recent reports suggest that it is not just the lung that the virus may be targeting; the human brain may soon emerge as the new abode of the virus. Already instances of patients with COVID-19 have been reported with mild (anosmia and ageusia) to severe (encephalopathy) neurological manifestations, and if that is so, then it gives us more reasons to be frightened of this killer virus. Keeping in mind that the situation does not worsen from here, immediate awareness and more thorough research regarding the neuroinvasive nature of the virus is the immediate need of the hour. Scientists globally also need to up their game to design more specific therapeutic strategies with the available information to counteract the pandemic. In this Viewpoint, we provide a brief outline of the currently known neurological manifestations of COVID-19 and discuss some probable ways to design therapeutic strategies to overcome the present global crisis. url: https://doi.org/10.1021/acschemneuro.0c00201 doi: 10.1021/acschemneuro.0c00201 id: cord-257105-vrwuaknf author: Davies, Julie title: Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19 date: 2020-09-15 words: 2642.0 sentences: 141.0 pages: flesch: 47.0 cache: ./cache/cord-257105-vrwuaknf.txt txt: ./txt/cord-257105-vrwuaknf.txt summary: Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. This study presents a detailed in silico analysis of the expression of nrP1 in the human brain, highlighting the potential role of nrP1 as an additional SarS-coV-2 infection mediator in the CNS via NRP1-expressing cells. Given this newly identified role of nrP1 in enhancing SarS-coV-2 entry into the cnS, characterizing the precise expression of nrP1 in the human brain becomes important in the context of the neurologic involvement of coVid-19. Finally, the parolfactory gyri which receive inputs from the olfactory bulb and provide input to the limbic system, also exhibit nrP1 expression, and so their potential involvement in the SarS-coV-2 infection of the cnS merits further research. abstract: Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the cause of the new viral infectious disease (coronavirus disease 2019; COVID-19). Emerging evidence indicates that COVID-19 may be associated with a wide spectrum of neurological symptoms and complications with central nervous system (CNS) involvement. It is now well-established that entry of SARS-CoV-2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensin-converting enzyme 2 (ACE-2). Preclinical studies have suggested that neuropilin-1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID-19 by enhancing the entry of SARS-CoV-2 into the brain through the olfactory epithelium. In the present study, we expand on these findings and demonstrate that the NRP1 is also expressed in the CNS, including olfactory-related regions such as the olfactory tubercles and paraolfactory gyri. This furthers supports the potential role of NRP1 as an additional SARS-CoV-2 infection mediator implicated in the neurologic manifestations of COVID-19. Accordingly, the neurotropism of SARS-CoV-2 via NRP1-expressing cells in the CNS merits further investigation. url: https://www.ncbi.nlm.nih.gov/pubmed/33000221/ doi: 10.3892/mmr.2020.11510 id: cord-342220-lrqt2gcw author: Dearlove, Bethany title: A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants date: 2020-09-22 words: 7874.0 sentences: 415.0 pages: flesch: 49.0 cache: ./cache/cord-342220-lrqt2gcw.txt txt: ./txt/cord-342220-lrqt2gcw.txt summary: Although the closest currently available bat sequences are fairly divergent from SARS-CoV-2, their characteristics (insertion at S1/S2 cleavage site, high diversity, and similarity between specific gene fragments and particular strains) together with their known adaptive properties (high recombination and host-switching rates and evidence of positive selection) support that these bat viruses constitute While the evolutionary rate is likely to decrease over time (18) , it is important to monitor the introduction of any mutation that may compromise the potential efficacy of vaccine candidates derived from the first available SARS-CoV-2 sequences. In S, only site 614 was estimated to be under diversifying selection in a majority of subsampled alignments (58%); evidence of diversifying selection indicates that genetic diversity increases in the viral population (i.e., there was a higher proportion of mutations causing an amino acid change than not at site 614, or, the nonsynonymous/synonymous substitution rates ratio, dN/dS, was over 1, P < 0.1) (SI Appendix, Fig. S4 ). abstract: The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages. url: https://doi.org/10.1073/pnas.2008281117 doi: 10.1073/pnas.2008281117 id: cord-285168-qkadqohe author: Delatorre, Edson title: Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries date: 2020-04-23 words: 2551.0 sentences: 149.0 pages: flesch: 55.0 cache: ./cache/cord-285168-qkadqohe.txt txt: ./txt/cord-285168-qkadqohe.txt summary: Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented. In some countries (Italy and Netherlands) community transmission was traced long before (2-4 weeks) the first confirmed SARS-CoV-2 infection case; while in others (Spain, France, United Kingdom, Germany, and Belgium) the onset date roughly coincides with the time of detection of the first imported cases (Figure 1 ). That quite long period of cryptic community transmission (> 4 weeks) in all analyzed countries draws attention to the great challenge of tracking the early global spread of SARS-CoV-2 and supports that control measures should be adopted at least as soon as first imported cases are detected in a new geographic region. abstract: The SARS-CoV-2 rapidly spread around the world during 2020, but the precise time in which the virus began to spread locally is currently unknown for most countries. Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented. url: https://doi.org/10.1101/2020.04.20.20073007 doi: 10.1101/2020.04.20.20073007 id: cord-290056-x74cq2k5 author: Delgado-Roche, Livan title: Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection date: 2020-04-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV), the pathogenic agent of Covid-19, represent a serious health problem worldwide. Respiratory viral infections are, in general, associated with cytokine production, inflammation, cell death, and other pathophysiological processes, which could be link with a redox imbalance or oxidative stress. These phenomena are substantially increased during aging. Actually, severity and mortality risk of SARS-CoV-2 infection or Covid-19 disease have been associated with the age. The aim of the present work was to contribute with the understanding of the possible link between oxidative stress and the pathogenesis, severity and mortality risk in patients affected by SARS-CoV infection. url: https://api.elsevier.com/content/article/pii/S0188440920305403 doi: 10.1016/j.arcmed.2020.04.019 id: cord-266511-g5h4tazp author: Deslandes, A title: SARS-COV-2 was already spreading in France in late December 2019 date: 2020-05-03 words: 1369.0 sentences: 93.0 pages: flesch: 58.0 cache: ./cache/cord-266511-g5h4tazp.txt txt: ./txt/cord-266511-g5h4tazp.txt summary: We report here a case of a patient hospitalized in December 2019 in our intensive care, of our hospital in the north of Paris, for hemoptysis with no etiological diagnosis and for which RT-PCR was performed retrospectively on the stored respiratory sample which confirmed the diagnosis of COVID-19 infection. After its onset in December 2019 in China, the new coronavirus (SARS-COV-2) spreads widely in several countries, causing COVID-19 illness. 8 Clinical symptomatology between COVID-19 and ILIis similar,we therefore decided retrospectively to look for SARS-COV2 in respiratory samples collected in the intensive care units (ICUs) of our hospital near Paris. We reviewed medical record of ICUs patients admitted for ILI between December 2, 2019 and January 16, 2020, with a negative RT-PCR performed at admission. Samples taken from patients with both ILI symptoms (fever higher than 38.5°C, cough, rhinitis, sore throat or myalgia) and ground glass opacity according to their medical record underwent SARS-COV-2 RT-PCR. abstract: Abstract The COVID-19 epidemic is believed to have started in late January 2020 in France. We report here a case of a patient hospitalized in December 2019 in our intensive care, of our hospital in the north of Paris, for hemoptysis with no etiological diagnosis and for which RT-PCR was performed retrospectively on the stored respiratory sample which confirmed the diagnosis of COVID-19 infection. Based on this result, it appears that the COVID-19 epidemic started much earlier. url: https://www.sciencedirect.com/science/article/pii/S0924857920301643?v=s5 doi: 10.1016/j.ijantimicag.2020.106006 id: cord-279255-v861kk0i author: Dhama, Kuldeep title: Coronavirus Disease 2019–COVID-19 date: 2020-06-24 words: 23862.0 sentences: 1164.0 pages: flesch: 44.0 cache: ./cache/cord-279255-v861kk0i.txt txt: ./txt/cord-279255-v861kk0i.txt summary: Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID19) , emerged in late 2019, and it has posed a global health threat, causing an ongoing pandemic in many countries and territories (1) . Health workers worldwide are currently making efforts to control further disease outbreaks caused by the novel CoV (originally named 2019-nCoV), which was first identified in Wuhan City, Hubei Province, China, on 12 December 2019. abstract: In recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus. url: https://www.ncbi.nlm.nih.gov/pubmed/32580969/ doi: 10.1128/cmr.00028-20 id: cord-327063-ea7a1xfl author: Dhama, Kuldeep title: SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus date: 2020-08-02 words: 11048.0 sentences: 600.0 pages: flesch: 48.0 cache: ./cache/cord-327063-ea7a1xfl.txt txt: ./txt/cord-327063-ea7a1xfl.txt summary: The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARSand MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease. Further research exploring the SARS-CoV-2 associated zoonosis and mechanisms accounting for its initial transmission from animals to humans, will lead to sort out the spread of this virus as well as design and develop appropriate prevention and control strategies to counter COVID-19. The present comprehensive manuscript presents an overview on COVID-19, an emerging SARS-CoV-2 infectious disease while focusing mainly on the events and circumstantial evidences with regards to this virus jumping the species barriers, sharing a few lessons learned from SARS-and MERS-CoVs, zoonotic spillover events (zoonosis), acquiring transmission ability to infect humans, and adopting appropriate preventive and control measures [42] . abstract: Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in China in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11). COVID-19 has presently spread to more than 215 countries/territories while killing nearly 0.62 million humans out of cumulative confirmed infected asymptomatic or symptomatic cases accounting to almost 15 million as of July 22, 2020, within a short period of just a few months. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of the animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter the COVID-19. The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease. url: https://api.elsevier.com/content/article/pii/S1477893920303264 doi: 10.1016/j.tmaid.2020.101830 id: cord-266885-a5fdeuvv author: Dlotko, P. title: Covid-19 clinical data analysis using Ball Mapper date: 2020-04-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In this note we provide a result of analysis of blood test data from patients with SARS-Cov-2 using Ball Mapper Algorithm. We observe that patients with the virus and in particularly patients who end up in Intensive Care Unit have quite narrow values of those parameters. Please note that this is a preliminary work and it need to be validated on much larger dataset which we are trying to acquire at the moment. url: http://medrxiv.org/cgi/content/short/2020.04.10.20061374v1?rss=1 doi: 10.1101/2020.04.10.20061374 id: cord-266444-rw94yls8 author: Dominguez Andres, Ana title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summary SARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection. url: https://doi.org/10.1101/2020.08.18.256776 doi: 10.1101/2020.08.18.256776 id: cord-333682-ktbnrkwh author: Dong, Yunzhu title: Antibodies in the breast milk of a maternal woman with COVID-19 date: 2020-07-03 words: 1332.0 sentences: 82.0 pages: flesch: 58.0 cache: ./cache/cord-333682-ktbnrkwh.txt txt: ./txt/cord-333682-ktbnrkwh.txt summary: A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Although clinical and laboratory characteristics, and outcomes of pregnant women with COVID-19 have been reported [4], there are no continuously monitored data about the viral loads in several body fluids of the maternal women that would bring potential risks of SARS-CoV-2 infection to neonates [8] . The titers of IgG antibody in breast milk were 2.34, 3.02, 2.84, 2.79, and 3.35, respectively, when three SARS-CoV-2 negative maternal woman''s breast milk were tested as control (mean titer 0.98) (Figure 1, panel D) . (D) Titers of IgG antibody to SARS-CoV-2 in maternal woman''s breast milk determined using ELISA. abstract: A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Her infant negative for SARS-CoV-2 at birth had elevated IgG in serum but quickly decayed. These findings suggest that breastfeeding might have the potential benefit to the neonates. url: https://www.ncbi.nlm.nih.gov/pubmed/32552365/ doi: 10.1080/22221751.2020.1780952 id: cord-350959-bsbz3a1l author: Dovey, Zachary title: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists date: 2020-06-16 words: 5079.0 sentences: 241.0 pages: flesch: 47.0 cache: ./cache/cord-350959-bsbz3a1l.txt txt: ./txt/cord-350959-bsbz3a1l.txt summary: There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes. As shown in Table 2 , PCa patients with either diabetes or hypertension should seek advice from their physicians to optimize their treatment, especially if this includes ACE inhibitors or ARBs [32] , to reduce their risk of SARS-CoV-2 infection and morbidity. Tewari Prostate cancer (PCa) patients may have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality. abstract: Abstract Context The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Objective To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. Evidence acquisition A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. Evidence synthesis A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. Conclusions PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes. url: https://www.sciencedirect.com/science/article/pii/S2666168320351120?v=s5 doi: 10.1016/j.euros.2020.05.005 id: cord-308583-vtmwv8zl author: Du, Qishi title: Molecular modeling and chemical modification for finding peptide inhibitor against severe acute respiratory syndrome coronavirus main proteinase date: 2005-02-15 words: 3856.0 sentences: 225.0 pages: flesch: 63.0 cache: ./cache/cord-308583-vtmwv8zl.txt txt: ./txt/cord-308583-vtmwv8zl.txt summary: In this research we study the cleavage mechanism, the properties of the relevant chemical bonds, and the catalytic interactions between the octapeptides and the SARS CoV M pro using molecular mechanical and quantum chemical simulations to provide useful insights for the chemical modification. The docking calculation between SARS CoV M pro and the octapeptide AVLQSGFR was performed using the molecular although still bound to the active site, the peptide has lost its cleavability after its scissile bond was modified from a hybrid peptide bond to a strong bond. Fig. 5B is the contour map of differential electronic density of the peptide bond Gln-Ser in the octapeptide AVLQSGFR, obtained by subtracting the electron density in the gaseous phase from the electron density in the background [23] of SARS CoV M pro and solvent water molecules. For the peptide inhibitor of proteinase, the chemical modification to cleavable octapeptide should focus on the scissile peptide bond between R 1 and R 1 0 to be cleaved by SARS CoV M pro . abstract: Abstract Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a newly found virus, called SARS coronavirus. In this study, the cleavage mechanism of the SARS coronavirus main proteinase (Mpro or 3CLpro) on the octapeptide NH2-AVLQ↓SGFR-COOH was investigated using molecular mechanics and quantum mechanics simulations based on the experimental structure of the proteinase. It has been observed that the catalytic dyad (His-41/Cys-145) site between domains I and II attracts the π electron density from the peptide bond Gln–Ser, increasing the positive charge on C(CO) of Gln and the negative charge on N(NH) of Ser, so as to weaken the Gln–Ser peptide bond. The catalytic functional group is the imidazole group of His-41 and the S in Cys-145. Nδ1 on the imidazole ring plays the acid–base catalytic role. Based on the “distorted key theory” [K.C. Chou, Anal. Biochem. 233 (1996) 1–14], the possibility to convert the octapeptide to a competent inhibitor has been studied. It has been found that the chemical bond between Gln and Ser will become much stronger and no longer cleavable by the SARS enzyme after either changing the carbonyl group CO of Gln to CH2 or CF2 or changing the NH of Ser to CH2 or CF2. The octapeptide thus modified might become an effective inhibitor or a potential drug candidate against SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/15691506/ doi: 10.1016/j.ab.2004.10.003 id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 words: 7346.0 sentences: 386.0 pages: flesch: 46.0 cache: ./cache/cord-328003-yovp8squ.txt txt: ./txt/cord-328003-yovp8squ.txt summary: Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/33117378/ doi: 10.3389/fimmu.2020.576622 id: cord-343317-97n1j0jj author: Duan, Xiaohua title: Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date: 2020-05-02 words: 3776.0 sentences: 222.0 pages: flesch: 56.0 cache: ./cache/cord-343317-97n1j0jj.txt txt: ./txt/cord-343317-97n1j0jj.txt summary: Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. The organoids infected with SARS-CoV-2 pseudo-entry virus at MOI=0.01 showed a strong signal at 24 hpi (Fig. 2a) . The mRNAs of SARS-CoV-2 pseudo-entry virus, including VSV-NS, VSV-N, and VSV-M, were detected in all five cell populations (Fig. 2f) , but not in the uninfected COs (Extended Data Fig. 2f) . Immunohistochemistry detected luciferase in ACE2 + and Villin + cells, suggesting these are permissive to SARS-CoV-2 pseudo-entry virus infection in vivo (Fig. 2k) . Next, we adapted hPSC-COs to a high throughput screening platform and probed the Prestwick FDA-approved drug library to identify drug candidates capable of blocking SARS-CoV-2 pseudo-virus infection. abstract: The current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing. url: https://doi.org/10.1101/2020.05.02.073320 doi: 10.1101/2020.05.02.073320 id: cord-294108-uvnh0s9r author: Dube, Taru title: Repurposed Drugs, Molecular Vaccines, Immune‐Modulators, and Nanotherapeutics to Treat and Prevent COVID‐19 Associated with SARS‐CoV‐2, a Deadly Nanovector date: 2020-10-25 words: 13885.0 sentences: 845.0 pages: flesch: 44.0 cache: ./cache/cord-294108-uvnh0s9r.txt txt: ./txt/cord-294108-uvnh0s9r.txt summary: [2, [8] [9] [10] This article discusses SARS-CoV-2 nanostructure, the virus biology in connection to its epidemiology, clinical manifestations, and potential and future therapeutic options including repurposed drugs, vaccine/protein therapies, immune therapies, and nanotherapeutics. Mechanisms such as inhibition of viral enzymes (DNA and RNA polymerases, 3CL pro, TMPRSS2, reverse transcriptase, neuraminidase, endonucleases, and other proteases) or processes such as ACE2 cellular receptor inhibitors and endosomal acidification mediators prohibiting viral fusion; molecules interfering with glycosylation of the viral protein, viral assembly, new viral particle transport, and release, and immunomodulation of cytokine release can be potential targets in developing various antiviral drugs for the SARS-CoV-2. [85] A randomized, placebo-controlled, Phase IV clinical trial assessing the safety and efficacy of umifenovir as an adjuvant therapy to the combined therapeutic regimen of IFN 1a, lopinavir/ritonavir and hydroxychloroquine in moderate to severe COVID-19 patients (NCT04350684) is underway. abstract: The deadly pandemic, coronavirus disease 2019 (COVID‐19), caused due to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has paralyzed the world. Although significant methodological advances have been made in the field of viral detection/diagnosis with 251 in vitro diagnostic tests receiving emergency use approval by the US‐FDA, little progress has been made in identifying curative or preventive therapies. This review discusses the current trends and potential future approaches for developing COVID‐19 therapeutics, including repurposed drugs, vaccine candidates, immune‐modulators, convalescent plasma therapy, and antiviral nanoparticles/nanovaccines/combinatorial nanotherapeutics to surmount the pandemic viral strain. Many potent therapeutic candidates emerging via drug‐repurposing could significantly reduce the cost and duration of anti‐COVID‐19 drug development. Gene/protein‐based vaccine candidates that could elicit both humoral and cell‐based immunity would be on the frontlines to prevent the disease. Many emerging nanotechnology‐based interventions will be critical in the fight against the deadly virus by facilitating early detection and enabling target oriented multidrug therapeutics. The therapeutic candidates discussed in this article include remdesivir, dexamethasone, hydroxychloroquine, favilavir, lopinavir/ritonavir, antibody therapeutics like gimsilumab and TJM2, anti‐viral nanoparticles, and nanoparticle‐based DNA and mRNA vaccines. url: https://doi.org/10.1002/adtp.202000172 doi: 10.1002/adtp.202000172 id: cord-317355-z5tk3v3b author: Dunker, Susanne title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread date: 2020-10-13 words: 1954.0 sentences: 139.0 pages: flesch: 62.0 cache: ./cache/cord-317355-z5tk3v3b.txt txt: ./txt/cord-317355-z5tk3v3b.txt summary: title: No SARS-CoV-2 detected in air samples (pollen and particulate matter) in Leipzig during the first spread Air samples collected at our measuring station in Leipzig and purified pollen were analyzed for SARS-CoV-2 typical signals or for virus-induced cytopathic effects, to test if the virus could bind to bioaerosols and if so, whether these complexes are infectious. We therefore aimed at investigating whether SARS-CoV-2 can bind to pollen or other kind of particulate matter within bioaerosols sampled at our station in Leipzig and if so, whether these complexes are infectious. In none of these samples SARS-CoV-2 typical For a detailed analysis of a possible correlation between concentrations of the most abundant pollen, particulate matter and registered Covid-19 cases, a correlation matrix was created with R (package "PerformanceAnalytics") (Fig. 2) . abstract: The SARS-CoV-2 pandemic co-occurred with pollen season in Europe 2020 and recent studies suggest a potential link between both. Air samples collected at our measuring station in Leipzig and purified pollen were analyzed for SARS-CoV-2 typical signals or for virus-induced cytopathic effects, to test if the virus could bind to bioaerosols and if so, whether these complexes are infectious. The results show that neither air samples nor purified pollen were infectious or could act as carrier for virus particles. url: https://api.elsevier.com/content/article/pii/S0048969720364111 doi: 10.1016/j.scitotenv.2020.142881 id: cord-273182-djb0ozrt author: Díez, José María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-09-09 words: 4326.0 sentences: 260.0 pages: flesch: 50.0 cache: ./cache/cord-273182-djb0ozrt.txt txt: ./txt/cord-273182-djb0ozrt.txt summary: Recently, we reported cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2 and MERS-CoV with Flebogamma R DIF 5 and 10% and Gamunex R -C, two currently available intravenous IGs (IVIG) [23] . Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2 and MERS-CoV by: ELISA techniques; and well-established neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT 50 titers ranging from 4.5 to >5 (Figure 2 ). This neutralizing activity correlates with the cross-reactivity to different coronavirus antigens observed in ELISA-binding assays with IVIG, as shown in a previous study [23] . • Intravenous immunoglobulin products were tested against severe acute respiratory syndrome coronavirus 2 in cell culture neutralization assays. abstract: Background: Cross-reactivity against human coronaviruses with Flebogamma(®) DIF and Gamunex(®)-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32900263/ doi: 10.2217/imt-2020-0220 id: cord-296237-i9cti2ok author: Díez, José-María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 words: 3741.0 sentences: 220.0 pages: flesch: 51.0 cache: ./cache/cord-296237-i9cti2ok.txt txt: ./txt/cord-296237-i9cti2ok.txt summary: Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ). abstract: Background There is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy. Methods The neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%). Results All IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management. url: https://doi.org/10.1101/2020.06.19.160879 doi: 10.1101/2020.06.19.160879 id: cord-353524-3w970ycx author: Dömling, Alexander title: Chemistry and Biology of SARS-CoV-2 date: 2020-05-22 words: 3942.0 sentences: 237.0 pages: flesch: 52.0 cache: ./cache/cord-353524-3w970ycx.txt txt: ./txt/cord-353524-3w970ycx.txt summary: Given that SARS-CoV-2 and SARS-CoV share very high identical sequence in their 3CLpro, these HIV protease inhibitors are currently again repurposed for the treatment of COVID-19 (Chinese Clinical Trial Registry: ChiCTR2000029539). 30, 31 The interplay of the ACE receptor in cardiovascular diseases (with the well-known drug class of ACE inhibitors) and as the docking point for SARS-CoV-2 cellular infection is a current point of intense debate and research. For example, the crystal structure of SARS-CoV-2 N protein RNA-binding domain was just published and will give structural insight as a potential drug target. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites abstract: SARS-CoV-2 (previously 2019-nCoV or Wuhan coronavirus) caused an unprecedented fast-spreading worldwide pandemic. Although currently with a rather low mortality rate, the virus spread rapidly over the world using the modern world’s traffic highways. The coronavirus (CoV) family members were responsible for several deadly outbreaks and epidemics during the last decade. Not only governments but also the scientific community reacted promptly to the outbreak, and information is shared quickly. For example, the genetic fingerprint was shared, and the 3D structure of key proteins was rapidly solved, which can be used for the discovery of potential treatments. An overview is given on the current knowledge of the spread, disease course, and molecular biology of SARS-CoV-2. We discuss potential treatment developments in the context of recent outbreaks, drug repurposing, and development timelines. url: https://www.sciencedirect.com/science/article/pii/S2451929420301959 doi: 10.1016/j.chempr.2020.04.023 id: cord-315685-ute3dxwu author: Ehaideb, Salleh N. title: Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review date: 2020-10-06 words: 5542.0 sentences: 352.0 pages: flesch: 48.0 cache: ./cache/cord-315685-ute3dxwu.txt txt: ./txt/cord-315685-ute3dxwu.txt summary: The systematic search identified 101 studies and 326 preprints, of which 400 articles were excluded because they were reviews, non-original articles, unrelated to the COVID-19 infection, or experimental animals that do not support SARS-CoV-2 replication such as pigs, ducks, and chickens ( Fig. 1 and Additional file 2). The aims were to investigate the pathogenesis of COVID-19 (n = 15), testing drugs and vaccines (n = 14), the host Table 1 Search strategy and selection criteria We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research describing or using an animal model of SARS-CoV-2 induced COVID published in English from January 1, 2020, to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). abstract: BACKGROUND: Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19. METHODS: We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. RESULT: Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy. CONCLUSIONS: Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/33023604/ doi: 10.1186/s13054-020-03304-8 id: cord-307489-2liu4anc author: Elavia, Nasha title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia date: 2020-05-23 words: 1321.0 sentences: 72.0 pages: flesch: 43.0 cache: ./cache/cord-307489-2liu4anc.txt txt: ./txt/cord-307489-2liu4anc.txt summary: title: An Atypical Presentation of Acute Pulmonary Embolism With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia Clinical presentation and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies greatly amongst patients, as supported by recent literature. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) presenting with atypical gastrointestinal symptoms in a patient with SARS-CoV-2 infection. This atypical presentation of PE is unique to our case and highlights the significance of a high index of clinical suspicion for SARS-CoV-2 and its associated thrombogenic effect, even in patients with atypical symptoms. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) in a patient with SARS-CoV-2 pneumonia who mainly presented with gastrointestinal symptoms. Our patient however presented mainly with gastrointestinal symptoms, which have been reported with SARS-CoV-2; however, with significant hypoxia in the absence of a respiratory viral syndrome although with a low pretest probability for PE, we decided to further evaluate the patient for hypoxia. abstract: Clinical presentation and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies greatly amongst patients, as supported by recent literature. This poses an ongoing challenge in the diagnostic and therapeutic approach for managing these patients. Here, we would like to describe a case of acute bilateral pulmonary embolism (PE) presenting with atypical gastrointestinal symptoms in a patient with SARS-CoV-2 infection. This atypical presentation of PE is unique to our case and highlights the significance of a high index of clinical suspicion for SARS-CoV-2 and its associated thrombogenic effect, even in patients with atypical symptoms. url: https://www.ncbi.nlm.nih.gov/pubmed/32596069/ doi: 10.7759/cureus.8249 id: cord-315064-2mgv9j6n author: Escher, Felicitas title: Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies date: 2020-06-12 words: 3813.0 sentences: 241.0 pages: flesch: 48.0 cache: ./cache/cord-315064-2mgv9j6n.txt txt: ./txt/cord-315064-2mgv9j6n.txt summary: Accordingly, we prospectively analysed endomyocardial biopsies (EMBs) from a cohort of 104 samples of patients with suspected myocarditis or unexplained heart disease for the presence of SARS-CoV-2 RNA by RT-qPCR and hints for histopathological injury. Up to 8 EMBs each of 104 patients [mean age: 57.90 ± 16.37 years; left ventricular ejection fraction (LVEF): 33.7 ± 14.6%, sex: n = 79 male/25 female] with suspected myocarditis or unexplained heart failure were analysed between 3 February and 26 March 2020 in German clinical centres in accordance with SARS-CoV2 spread in Germany. In this study, we established for the first time the evidence of SARS-CoV-2 genome detection in 5 of 104 EMBs of patients with suspected myocarditis or unexplained heart failure. Our finding of SARS-CoV-2 genome detection in EMBs of patients suffering from myocarditis/inflammatory cardiomyopathy cannot rule out or confirm the infection of cardiac cells but revealed incremental insights into organ-specific infection of SARS-CoV-2 using possibly macrophage migration as a shuttle from the lung to the heart. abstract: AIMS: Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported. SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. METHODS AND RESULTS: Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. CONCLUSIONS: This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies. url: https://www.ncbi.nlm.nih.gov/pubmed/32529795/ doi: 10.1002/ehf2.12805 id: cord-277399-0w8is9xm author: Esteves, Sandro C. title: SARS‐CoV‐2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services date: 2020-05-22 words: 4160.0 sentences: 216.0 pages: flesch: 38.0 cache: ./cache/cord-277399-0w8is9xm.txt txt: ./txt/cord-277399-0w8is9xm.txt summary: The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation—as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto‐immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. Sperm banking should be considered in men with HH who respond to therapy, that is, have viable spermatozoa in the ejaculate, in particular, when the continuation of gonadotropin therapy during the SARS-CoV-2 pandemic is neither possible (eg, due to economic or logistic reasons), nor desired. We propose remedies to mitigate the consequences of a prolonged cessation of andrological services due to the SARS-CoV-2 pandemic to vulnerable subgroups of male infertility patients. abstract: The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation—as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto‐immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the “fertility window” may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries. url: https://www.ncbi.nlm.nih.gov/pubmed/32357288/ doi: 10.1111/andr.12809 id: cord-256020-wrui3i2l author: Fadaka, Adewale Oluwaseun title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 words: 7097.0 sentences: 465.0 pages: flesch: 49.0 cache: ./cache/cord-256020-wrui3i2l.txt txt: ./txt/cord-256020-wrui3i2l.txt summary: The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations abstract: The emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease. url: https://doi.org/10.1177/0300060520949077 doi: 10.1177/0300060520949077 id: cord-281684-m3m4mhye author: Fagre, Anna C. title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 words: 3707.0 sentences: 212.0 pages: flesch: 47.0 cache: ./cache/cord-281684-m3m4mhye.txt txt: ./txt/cord-281684-m3m4mhye.txt summary: title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. However, to date, there has been only a gross histological analysis of the lung pathological changes following infection and the impact of SARS-CoV-2 neutralizing antibody clones on lung immune infiltrates has yet to be fully assessed. Those antibody clones that blocked the interaction of the RBD with ACE2 and bound to native spike protein were then tested for neutralization of SARS-CoV-2 in a cytopathic effect (CPE) assay with Vero E6 cells. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity abstract: The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients. url: https://doi.org/10.1101/2020.09.25.313601 doi: 10.1101/2020.09.25.313601 id: cord-318204-t024w7h6 author: Fang, Ferric C title: The Laboratory Diagnosis of COVID-19-- Frequently-Asked Questions date: 2020-06-08 words: 2976.0 sentences: 218.0 pages: flesch: 51.0 cache: ./cache/cord-318204-t024w7h6.txt txt: ./txt/cord-318204-t024w7h6.txt summary: As communities attempt to re-open following periods of shutdown, the detection of both SARS-CoV-2 and specific antibodies recognizing the virus will become increasingly important as a means to assess infection and immunity in individuals and communities. In view of the less than ideal sensitivity of an NP swab to detect SARS-CoV-2 infection, it may be useful to repeat testing in a patient in whom the clinical suspicion is high (32) . Although the primary use of serologic tests is to determine prior exposure to SARS-CoV-2, the detection of specific antibodies may support the diagnosis of COVID-19 in a patient with a high clinical suspicion but negative PCR tests (57-59). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection abstract: Diagnostic testing has played and will continue to play a major role in the COVID-19 pandemic. The ability to detect the SARS-CoV-2 coronavirus in respiratory secretions is essential to determine when an individual is infected and potentially infectious to others. Viral detection is used for the identification, management and isolation of individual patients. Viral detection is also used to determine when the virus has entered a community and how rapidly it is spreading. As communities attempt to re-open following periods of shutdown, the detection of both SARS-CoV-2 and specific antibodies recognizing the virus will become increasingly important as a means to assess infection and immunity in individuals and communities. Here we discuss questions commonly asked by clinicians about COVID-19 diagnostic testing. url: https://www.ncbi.nlm.nih.gov/pubmed/32511679/ doi: 10.1093/cid/ciaa742 id: cord-313344-rqvi2ksc author: Farcas, Gabriella A. title: Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus date: 2005-01-15 words: 2427.0 sentences: 104.0 pages: flesch: 46.0 cache: ./cache/cord-313344-rqvi2ksc.txt txt: ./txt/cord-313344-rqvi2ksc.txt summary: Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). The purpose of the present study was to investigate the presence of SARS-CoV, the degree of viral dissemination, and the viral loads in multiple organ samples from all patients who died of SARS during the Toronto outbreak (March to September 2003) and underwent a postmortem examination and compare the results with those found in patients who died of other causes during the outbreak. A total of 212 discrete postmortem organ samples, including lung, liver, spleen, kidney, small bowel, large bowel, lymph nodes, heart, and skeletal muscle, were prospectively collected from the 21 patients who died of SARS and underwent autopsies. abstract: Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). We report on the distribution and viral load of SARS-CoV in multiple organ samples from patients who died of SARS during the Toronto outbreak. SARS-CoV was detected in lung (100%), bowel (73%), liver (41%), and kidney (38%) in 19 patients who died of SARS, with the highest viral loads observed in lung (1.0 × 10(10) copies/g) and bowel (2.7 × 10(9) copies/g). Fatal SARS was associated with multiorgan viral dissemination in a distribution that has implications for disease manifestation, viral shedding, and transmission. url: https://www.ncbi.nlm.nih.gov/pubmed/15609228/ doi: 10.1086/426870 id: cord-298850-tgxfki7n author: Figuero-Pérez, Luis title: Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab date: 2020-10-15 words: 1027.0 sentences: 84.0 pages: flesch: 49.0 cache: ./cache/cord-298850-tgxfki7n.txt txt: ./txt/cord-298850-tgxfki7n.txt summary: title: Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra). We present the case of a 51-year-old patient with bilateral pneumonia secondary to SARS-CoV-2 infection refractory to treatment with tocilizumab who showed improvement after treatment with anakinra. The "cytokine storm" secondary to SARS-CoV-2 infection determines severe COVID-19 disease. 3 The use of anti-IL-6 antibodies in the treatment of SARS-CoV-2 infection is currently under study, being one of the current pillars of COVID-19 disease treatment. abstract: SARS-CoV-2 is a new RNA virus which causes coronavirus disease 2019 (COVID-19), declared a pandemic by the World Health Organization (WHO). It triggers an atypical pneumonia that can progress to multiorgan failure. COVID-19 can cause dysregulation of the immune system, triggering an inflammatory response, and simulate haemophagocytic lymphohistiocytosis. Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. However, the role of anti-IL-1 receptor antibodies, such as anakinra, in the treatment of COVID-19 has not been established. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra). url: https://api.elsevier.com/content/article/pii/S2173574320301313 doi: 10.1016/j.reumae.2020.06.008 id: cord-339009-wcoch07b author: File, Thomas M. title: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy date: 2012-08-23 words: 6023.0 sentences: 324.0 pages: flesch: 50.0 cache: ./cache/cord-339009-wcoch07b.txt txt: ./txt/cord-339009-wcoch07b.txt summary: Because the causative agent of SARS is • one or more clinical findings of respiratory illness (e.g. cough, contagious, preventative measures focus on avoidance of exposhortness of breath, difficulty in breathing, or hypoxia) sure, and infection control strategies for suspected patients and • travel within 10 days of onset of symptoms to an area with contacts. [12] Of the reported cases was updated to include laboratory criteria for evidence of infection 64% were from China, 19% from Hong Kong, 8% from Taiwan, with the SARS-associated coronavirus (SARS-CoV). Algorithm for evaluating and managing patients requiring hospitalization for radiographically confirmed pneumonia, in the absence of person-toperson transmission of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) anywhere in the world. abstract: Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/15813661/ doi: 10.2165/00151829-200504020-00003 id: cord-252767-as841xo0 author: Fischer, Bastian title: SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020 date: 2020-07-16 words: 2028.0 sentences: 110.0 pages: flesch: 49.0 cache: ./cache/cord-252767-as841xo0.txt txt: ./txt/cord-252767-as841xo0.txt summary: We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. To determine an approximation of the actual rate of people who have recovered from COVID-19, representative of the German population, we determined the anti-SARS-CoV-2 IgG seroprevalence of regular blood donors resident in three different German federal states between March and June 2020. The Figure shows the anti-SARS-CoV-2 IgG distribution in blood donors with equivocal (ratio: ≥ 0.8 to < 1.1) and clearly seropositive (ratio: ≥ 1.1) test results. Distribution of anti-SARS-CoV-2 IgG ratios of blood donors with seropositive and equivocal test results, Germany, March-June 2020, (n = 3,186) abstract: Most cases of coronavirus disease 2019 are mild or asymptomatic. Therefore, many cases remain unrecorded. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. The IgG seroprevalence was 0.91% (95% confidence interval (CI): 0.58–1.24) overall, ranging from 0.66% (95% CI: 0.13–1.19) in Hesse to 1.22% (95% CI: 0.33–2.10) in Lower-Saxony. url: https://www.ncbi.nlm.nih.gov/pubmed/32700672/ doi: 10.2807/1560-7917.es.2020.25.28.2001285 id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 words: 15130.0 sentences: 700.0 pages: flesch: 44.0 cache: ./cache/cord-264814-v4wnmg03.txt txt: ./txt/cord-264814-v4wnmg03.txt summary: Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. abstract: There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery. url: https://doi.org/10.3389/fimmu.2020.579250 doi: 10.3389/fimmu.2020.579250 id: cord-310624-3kojrkz7 author: Flores-Alanis, Alejandro title: The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789 date: 2020-08-27 words: 3064.0 sentences: 181.0 pages: flesch: 56.0 cache: ./cache/cord-310624-3kojrkz7.txt txt: ./txt/cord-310624-3kojrkz7.txt summary: In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans. RESULTS: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved. abstract: OBJECTIVE: In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans. RESULTS: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved. url: https://doi.org/10.1186/s13104-020-05242-8 doi: 10.1186/s13104-020-05242-8 id: cord-275926-rj23z7po author: Fontanella, Marco M. title: Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey date: 2020-05-05 words: 4013.0 sentences: 234.0 pages: flesch: 52.0 cache: ./cache/cord-275926-rj23z7po.txt txt: ./txt/cord-275926-rj23z7po.txt summary: 3. Institutional plans for the SARS-CoV-2 outbreak: any special measures adopted for SARS-CoV-2 positive neurosurgical patients were investigated, i.e. their screening rate and method, any changes in surgical indications, planning and activity for oncologic procedures, non-emergency surgeries, and subarachnoid hemorrhages (SAHs). The same correlation was found with regards to the medical perception of disease activity (Q2) in different countries, and only few respondents (3%) claimed their country was not facing the outbreak during the time period studied: among them, neurosurgeons from Germany were probably the most "wrong", since their country had between 10 4 to 10 5 SARS-CoV2 patients during the study period (Fig. 4A) . 5 India and Pakistan have been reported to be the world''s best respondents to the SARS-COV-2 pandemic, 22-24 thus reflecting high rates of neurosurgical activity reorganizations. abstract: Abstract Background and Objective The SARS-CoV-2 pandemic has consistently changed medical practice throughout specialties, regardless of their contribution in facing the disease itself. We surveyed neurosurgeons worldwide to investigate the situation they are experiencing. Design and participants A 17-question, web-based survey was administered to neurosurgeons worldwide through the WFNS and the Neurosurgery Cocktail from March 28 to April 5, 2020 by web link or e-mail invitation. Questions were divided into three subgroups: general information, health system organization, and institutional plans for the SARS-CoV-2 outbreak. Collected data was initially elaborated using Survey Monkey® software. Country specific data were extracted from the WHO website. Statistical analysis was performed using R version 3.6.3. Results Of the 446 respondents, most were from Italy (20%), India (19%), and Pakistan (5%). Surgical activity was significantly reduced in most centers (79%) and dedicated in-hospital routes were created for SARS-CoV-2 patients (58%). Patient screening was performed only when there were symptoms (57%) and not routinely before surgery (18%). The preferred methods included a nasopharyngeal swab and chest x-ray. Health professionals were rarely screened (20%) and sometimes, even if SARS-CoV-2 positive, were asked to work if asymptomatic (26%). Surgical planning was changed in most institutions (92%), while indications were modified for non-urgent procedures (59%) and remained unchanged for subarachnoid hemorrhages (85%). Conclusions Most neurosurgeons worldwide reported work reorganization and practices that respond to current international guidelines. Differences in practice might be related to the perception of the pandemic and significant differences in the health systems. Sharing data and experiences will be of paramount importance to address the present moment and challenges in the near future. url: https://www.sciencedirect.com/science/article/pii/S1878875020309141?v=s5 doi: 10.1016/j.wneu.2020.04.204 id: cord-019048-29wzpwvr author: Franks, Teri J. title: Coronavirus date: 2013-08-26 words: 2805.0 sentences: 135.0 pages: flesch: 47.0 cache: ./cache/cord-019048-29wzpwvr.txt txt: ./txt/cord-019048-29wzpwvr.txt summary: From discovery to mid-September 2013, HCoV-EMC, renamed MERS-CoV, (de Groot 2013 ) caused 132 laboratory-confi rmed cases of severe acute pneumonia including 58 deaths. Certain structural proteins are common to all coronaviruses: the spike glycoprotein S, an envelope glycoprotein that mediates receptor-binding and membrane fusion; the envelope spanning glycoprotein M, which contributes to the thickness of the envelop; the envelope protein E, which has been identifi ed as a virulence factor SARS-CoV ; and the nucleocapsid protein N, with its function in genome encapsidation, RNA synthesis and translation, and as a type I interferon antagonist ( Fig. 13 .2 ). Initial signs and symptoms of SARS are nonspecifi c and common, which generates a wide differential diagnosis of respiratory pathogens including infl uenza virus, parainfl uenza Fig. 13.4 Acute-phase DAD in SARS patient. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection abstract: Name of Virus: Coronavirus url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124098/ doi: 10.1007/978-3-642-40605-8_13 id: cord-254395-tu4aqczj author: Froggatt, Heather M. title: Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CL(pro) Reporter Assay date: 2020-10-27 words: 4200.0 sentences: 254.0 pages: flesch: 50.0 cache: ./cache/cord-254395-tu4aqczj.txt txt: ./txt/cord-254395-tu4aqczj.txt summary: This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. With the aim of generating a protease reporter compatible with SARS-CoV-2 and other present and future coronaviruses to support viral inhibitor screening, we selected CoV 3CL pro as our protease target. (C) Quantification of fluorescence from 293T cells 48 h after transfection with each FlipGFP reporter and either the SARS-CoV-2 3CL pro or an influenza virus protein (A/PR8/1834 NP). To observe whether these FlipGFP constructs background fluoresced without CoV 3CL pro activity, we transfected cells with each reporter or a superfolder GFP (sfGFP) expression plasmid. Development of a FlipGFP CoV 3CL pro reporter-based assay for protease inhibitor screening in human cells. abstract: In late 2019, a human coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, likely from a zoonotic reservoir. This virus causes COVID-19, has infected millions of people, and has led to hundreds of thousands of deaths across the globe. While the best interventions to control and ultimately stop the pandemic are prophylactic vaccines, antiviral therapeutics are important to limit morbidity and mortality in those already infected. At this time, only one FDA-approved anti-SARS-CoV-2 antiviral drug, remdesivir, is available, and unfortunately, its efficacy appears to be limited. Thus, the identification of new and efficacious antivirals is of the highest importance. In order to facilitate rapid drug discovery, flexible, sensitive, and high-throughput screening methods are required. With respect to drug targets, most attention is focused on either the viral RNA-dependent RNA polymerase or the main viral protease, 3CL(pro). 3CL(pro) is an attractive target for antiviral therapeutics, as it is essential for processing newly translated viral proteins and the viral life cycle cannot be completed without protease activity. In this work, we report a new assay to identify inhibitors of 3CL(pro). Our reporter is based on a green fluorescent protein (GFP)-derived protein that fluoresces only after cleavage by 3CL(pro). This experimentally optimized reporter assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible protocols. Using this screening approach in combination with existing drug libraries may lead to the rapid identification of novel antivirals to suppress SARS-CoV-2 replication and spread. IMPORTANCE The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes to daily life worldwide. Along with development of a vaccine, identification of effective antivirals to treat infected patients is of the highest importance. However, rapid drug discovery requires efficient methods to identify novel compounds that can inhibit the virus. In this work, we present a method for identifying inhibitors of the SARS-CoV-2 main protease, 3CL(pro). This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level 2 (BSL2) with high-throughput compatible sample processing and analysis. This assay may help identify novel antivirals to control the COVID-19 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32843534/ doi: 10.1128/jvi.01265-20 id: cord-313517-5ipj2z86 author: Fung, Joshua title: Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans date: 2019-09-14 words: 2710.0 sentences: 149.0 pages: flesch: 51.0 cache: ./cache/cord-313517-5ipj2z86.txt txt: ./txt/cord-313517-5ipj2z86.txt summary: Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus. Nucleic acid amplification test (NAAT, e.g., real-time reverse transcription quantitative polymerase chain reaction [real-time RT-qPCR]), virus isolation, transmission electron microscopy, immunohistochemistry, and serological methods (e.g., antigen capture enzyme-linked immunosorbent assay [ELISA] and immunofluorescence assay [IFA] ) have been developed and used for MERS-CoV diagnosis [2] [3] [4] [5] [6] [7] . abstract: The Middle East respiratory syndrome (MERS) is the second novel zoonotic disease infecting humans caused by coronavirus (CoV) in this century. To date, more than 2200 laboratory-confirmed human cases have been identified in 27 countries, and more than 800 MERS-CoV associated deaths have been reported since its outbreak in 2012. Rapid laboratory diagnosis of MERS-CoV is the key to successful containment and prevention of the spread of infection. Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus. url: https://doi.org/10.1007/978-1-0716-0211-9_7 doi: 10.1007/978-1-0716-0211-9_7 id: cord-322837-tqgwgvo0 author: Gable, Lance title: Legal and Ethical Implications of Wastewater SARS-CoV-2 Monitoring for COVID-19 Surveillance date: 2020-06-24 words: 1909.0 sentences: 104.0 pages: flesch: 47.0 cache: ./cache/cord-322837-tqgwgvo0.txt txt: ./txt/cord-322837-tqgwgvo0.txt summary: Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing, must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations. The proposed use of wastewater screening to detect SARS-CoV-2 viral RNA has the potential to greatly enhance our technical capabilities to identify, track, pinpoint, and quantify 32 Second, public health authorities could use this information to justify increased testing among people living in homes or working at sites close to where the virus has been found in wastewater, or to implement neighborhood-wide screening programs in these areas. Wastewater screening for SARS-CoV-2 could provide an important tool to detect new outbreaks of COVID-19 and to target resources to intervene to stop the spread of the disease; however, scientific research must establish the efficacy of such testing in identifying communitybased COVID-19 infections before its use can be considered as the basis for public policy. abstract: Scientists have observed that molecular markers for COVID-19 can be detected in wastewater of infected communities both during an outbreak and, in some cases, before the first case is confirmed. The CDC and other government entities are considering whether to add community surveillance through wastewater monitoring to assist in tracking disease prevalence and guiding public health responses to the COVID-19 pandemic. This scientific breakthrough may lead to many useful potential applications for tracking disease, intensifying testing, initiating social distancing or quarantines, and even lifting restrictions once a cessation of infection is detected and confirmed. Yet, new technologies developed in response to a public health crisis may raise difficult legal and ethical questions about how such technologies may impact both the public health and civil liberties of the population. This Article describes recent scientific evidence regarding COVID-19 detection in wastewater, identifying public health benefits that may result from this breakthrough, as well as the limitations of existing data. The Article then assesses the legal and ethical implications of implementing policy based on positive sewage signals. It concludes that the first step to implementing legal and ethical wastewater monitoring is to develop scientific understanding. Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing, must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations. url: https://doi.org/10.1093/jlb/lsaa039 doi: 10.1093/jlb/lsaa039 id: cord-252600-bvh1o64r author: Galasiti Kankanamalage, Anushka C. title: Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element date: 2018-04-25 words: 4752.0 sentences: 254.0 pages: flesch: 54.0 cache: ./cache/cord-252600-bvh1o64r.txt txt: ./txt/cord-252600-bvh1o64r.txt summary: We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ). abstract: Abstract There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography. url: https://www.ncbi.nlm.nih.gov/pubmed/29544147/ doi: 10.1016/j.ejmech.2018.03.004 id: cord-280774-r2xm164s author: Gallizzi, Romina title: Management of pernio‐like cutaneous manifestations in children during the outbreak of covid‐19. date: 2020-09-19 words: 2083.0 sentences: 128.0 pages: flesch: 47.0 cache: ./cache/cord-280774-r2xm164s.txt txt: ./txt/cord-280774-r2xm164s.txt summary: The increased number of cases of pernio-like lesions compared to the cases per year we usually observe, the mild temperatures of those months in Southern Italy and the concomitant lockdown, led us to hypothesize a possible correlation with SARS-CoV-2 infection. This is useful to highlight, as in our case, the D-dimer of our patients was weakly increased, a condition perfectly correlated with the mild symptoms of SARS-CoV-2 putative infection presented. In a report of 19 adolescent patients with a clinical diagnosis of pernio-like lesions nasopharyngeal swab and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Why some children who come into contact with the SARS-CoV-2 do not develop striking respiratory symptoms but present pernio-like lesions with negativity on diagnostic tests? This pathogenic mechanism could explain the appearance of pernio-like lesions due to SARS-CoV-2 infection. In conclusion, we think there is a correlation between pernio-like lesions and SARS-CoV-2 infection, but further studies are needed to prove it. abstract: BACKGROUND: During the outbreak of COVID‐19 many pernio‐like lesions have been increasingly reported. The aim of the study is to describe our management of these skin manifestations and to evaluate a possible correlation to SARS‐CoV‐2 infection. METHODS: All patients underwent clinical and laboratory tests to detect a possible underlying connective disease and also to specific SARS‐CoV‐2 investigations such as oropharyngeal swab and IgG‐IgM serology. RESULTS: Nine patients aged between five and fifteen years old were evaluated. Skin lesions observed were purplish, erythematous and oedematous, in some cases painful and itchy. Six out of nine had respiratory and systemic symptoms (cough, nasal congestion, chills, fever, asthenia) that preceded cutaneous findings of approximately two weeks. Concerning blood exams, three out of nine had D‐dimer weakly increased, four had ANA positivity: two with a title 1:160, one with 1:320 and one with 1:5120 and a speckled pattern. The latter patient had also ENA SS‐A positive and RF positivity, confirmed at a second check, so as to allow us to make a diagnosis of connective tissue disease. Four out of nine had aPL positivity (IgM). Reactants acute phase were all negative. Oropharyngeal swabs and serology tests for SARS‐CoV‐2 was negative (borderline in one patient for IgM). No treatment was needed. CONCLUSIONS: Even if we do not have enough data to prove it, we hypothesize a correlation between pernio‐like lesions and SARS‐CoV‐2 infection for an increased number of these lesions described during the pandemic and also because such manifestations appeared when temperatures were mild and patients were at home in isolation for the lockdown. Many questions remain open about interaction host‐virus. This article is protected by copyright. All rights reserved. url: https://www.ncbi.nlm.nih.gov/pubmed/32949449/ doi: 10.1111/dth.14312 id: cord-324102-75v4ebag author: Garcia Rodriguez, Alejandro title: SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report date: 2020-10-06 words: 1728.0 sentences: 110.0 pages: flesch: 49.0 cache: ./cache/cord-324102-75v4ebag.txt txt: ./txt/cord-324102-75v4ebag.txt summary: title: SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy. That is the reason why we present a case report of a pregnant woman infected with SARS-COV-2 who showed seizures and sudden blindness. Therefore, we consider that SARS-COV-2 infection during pregnancy could increase the risk of suffering posterior reversible leukoencephalopathy or preeclampsia/eclampsia syndrome. To our knowledge, this is the first report of a patient with COVID-19 presenting preeclampsia associated with eclampsia versus posterior reversible leukoencephalopathy without alarm signs or symptoms. We consider further studies are needed to confirm that SARS-COV-2 infection is a risk factor to develop neurological complications of pregnant woman during pregnancy. abstract: BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. We do not just face new and unknown manifestations, but also how different patient groups are affected by SARS-COV-2 infection, such as pregnant women. Coronavirus Disease 2019 (COVID-19), preeclampsia, eclampsia and posterior reversible leukoencephalopathy share endothelium damage and similar pathophysiology. CASE PRESENTATION: A 35-year-old pregnant woman was admitted for tonic-clonic seizures and SARS-COV-2 infection. She had a normal pregnancy control and no other symptoms before tonic-clonic seizures development. After a Caesarean section (C-section) she developed high blood pressure, and we initiated antihypertensive treatment with labetalol, amlodipine and captopril. Few hours later she developed symptoms of cortical blindness that resolved in 72 h with normal brain computed tomography (CT) angiography. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy. url: https://www.ncbi.nlm.nih.gov/pubmed/33023500/ doi: 10.1186/s12884-020-03275-2 id: cord-255552-k1retwa4 author: Gassen, Nils C. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 words: 1208.0 sentences: 73.0 pages: flesch: 39.0 cache: ./cache/cord-255552-k1retwa4.txt txt: ./txt/cord-255552-k1retwa4.txt summary: Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health and the world economy, especially because no approved specific drugs or vaccines are available. Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 propagation in vitro. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In sum, SARS-CoV-2 infection causally diminishes autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential for evaluation as a treatment against SARS-CoV-2. url: https://doi.org/10.1101/2020.04.15.997254 doi: 10.1101/2020.04.15.997254 id: cord-307701-fujejfwb author: Gaurav, Shubham title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 words: 2069.0 sentences: 111.0 pages: flesch: 54.0 cache: ./cache/cord-307701-fujejfwb.txt txt: ./txt/cord-307701-fujejfwb.txt summary: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the novel human Corona Virus Disease COVID-19, first reported on November 17 th , 2019 in Wuhan, China [12] . In addition to structural and NSPs, SARS-CoV-2 genome also codes for at least two other viroporin candidates (other than the E protein), namely ORF3a and ORF8 [3] . Moreover, the 29-nucleotide deleted SARS CoV-1 strain had a 23-fold less viral replication as compared to its wild type, suggesting that this mutation effectively attenuated the virus. abstract: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development. url: https://doi.org/10.1101/2020.06.06.137604 doi: 10.1101/2020.06.06.137604 id: cord-314135-udce22id author: Geisslinger, Franz title: Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa? date: 2020-07-06 words: 6414.0 sentences: 379.0 pages: flesch: 46.0 cache: ./cache/cord-314135-udce22id.txt txt: ./txt/cord-314135-udce22id.txt summary: The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. The main symptoms of COVID-19, the lung disease following SARS-CoV-2 infection are fever, cough, shortness of breath and respiratory distress syndrome with risk for septic shock. Preliminary evidence suggests that such a cytokine storm in response to infection with SARS-CoV-2 is a major factor, promoting severe COVID-19 progress and subsequently disease fatality [8, 12] . Chemotherapy-and radiation therapy-induced immunosuppression is a major risk factor for cancer patients to acquire a severe and probably fatal SARS-CoV-2 infection. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS † abstract: The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date. The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient. The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer. A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19. However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected. In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection. url: https://doi.org/10.3390/ph13070143 doi: 10.3390/ph13070143 id: cord-257399-p6of5fno author: Gentry, Chris A title: Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study date: 2020-09-21 words: 4529.0 sentences: 196.0 pages: flesch: 42.0 cache: ./cache/cord-257399-p6of5fno.txt txt: ./txt/cord-257399-p6of5fno.txt summary: METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. We aimed to examine whether patients with rheuma tological conditions receiving chronic hydroxy chloroquine therapy are at less risk of developing SARS-CoV-2 infection compared with a propensity-matched group of patients not receiving hydroxychloroquine. Our study takes advantage of a setting in which a specific group of patients has been receiving chronic hydroxy chloroquine over several months to years as a novel virus emerges among the population, setting up an ideal premise to test the hypothesis that hydroxychloroquine might be effective in preventing SARS-CoV-2 infection. abstract: BACKGROUND: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. FINDINGS: Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52–1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55–0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51–1·42). INTERPRETATION: Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. FUNDING: None. url: https://api.elsevier.com/content/article/pii/S2665991320303052 doi: 10.1016/s2665-9913(20)30305-2 id: cord-311848-8n9ee57a author: Giesen, Nicola title: Evidence-based Management of COVID-19 in Cancer Patients – Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) date: 2020-09-21 words: 7678.0 sentences: 516.0 pages: flesch: 48.0 cache: ./cache/cord-311848-8n9ee57a.txt txt: ./txt/cord-311848-8n9ee57a.txt summary: It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria. We do not 285 recommend to delay/discontinue radiotherapy, targeted therapy, endocrine therapy or surgery in 286 cancer patients without suspected/confirmed SARS-CoV-2 infection (DII u ) as no impact on mortality 287 of such prior treatments was seen in several large cohort studies of 20, 31, 40, 94 288 In patients with COVID-19, it is strongly recommended to delay/discontinue chemotherapy, if 289 possible, as chemotherapy within two weeks of admission was a major risk factor for severe COVID-290 19 in a large Chinese cohort study (AII u ). Clinical characteristics and risk factors 38 associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, 39 retrospective, cohort study abstract: Since its first detection in China in late 2019 the novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 continue to have a major impact on global health care and clinical practice. Cancer patients, in particular those with haematological malignancies, seem to be at an increased risk for a severe course of infection. Deliberations to avoid or defer potentially immunosuppressive therapies in these patients need to be balanced against the overarching goal of providing optimal antineoplastic treatment. This poses a unique challenge to treating physicians. This guideline provides evidence-based recommendations regarding prevention, diagnostics and treatment of SARS-CoV-2 infection and COVID-19 as well as strategies towards safe antineoplastic care during the COVID-19 pandemic. It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria. url: https://www.sciencedirect.com/science/article/pii/S0959804920304937?v=s5 doi: 10.1016/j.ejca.2020.09.009 id: cord-267115-6jqdi417 author: Giobbe, Giovanni Giuseppe title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date: 2020-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2. url: https://doi.org/10.1101/2020.06.24.167049 doi: 10.1101/2020.06.24.167049 id: cord-345356-gn1iwis0 author: Glebov, Oleg O. title: Understanding SARS‐CoV‐2 endocytosis for COVID‐19 drug repurposing date: 2020-06-02 words: 3502.0 sentences: 175.0 pages: flesch: 35.0 cache: ./cache/cord-345356-gn1iwis0.txt txt: ./txt/cord-345356-gn1iwis0.txt summary: Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS‐CoV‐2 infection needs to consider the diversity of endocytic pathways available for SARS‐CoV‐2 entry in the human lung epithelium. Taken together, the above evidence suggests that SARS-CoV-2 may employ distinct endocytic pathways for cell entry in the upper and lower respiratory tract (Fig. 1) . This approach would allow tracking of the virus in relation to other endocytic pathways and also to investigate the effect of viral infection on the general membrane trafficking network of the host cell. Taken together, the combination of adequate cell models with the newly developed SARS-CoV-2 toolkit and established tools of membrane trafficking research is well-poised to deliver a key insight into the mechanisms underlying COVID-19 infection. Furthermore, considering that various viruses may use the same endocytic pathways of the host cell [15] , targeting viral entry at the point of endocytosis holds a more general promise for the development of broad-spectrum antiviral drugs [51] . abstract: The quest for the effective treatment against coronavirus disease 2019 pneumonia caused by the severe acute respiratory syndrome (SARS)‐coronavirus 2(CoV‐2) coronavirus is hampered by the lack of knowledge concerning the basic cell biology of the infection. Given that most viruses use endocytosis to enter the host cell, mechanistic investigation of SARS‐CoV‐2 infection needs to consider the diversity of endocytic pathways available for SARS‐CoV‐2 entry in the human lung epithelium. Taking advantage of the well‐established methodology of membrane trafficking studies, this research direction allows for the rapid characterisation of the key cell biological mechanism(s) responsible for SARS‐CoV‐2 infection. Furthermore, 11 clinically approved generic drugs are identified as potential candidates for repurposing as blockers of several potential routes for SARS‐CoV‐2 endocytosis. More broadly, the paradigm of targeting a fundamental aspect of human cell biology to protect against infection may be advantageous in the context of future pandemic outbreaks. url: https://www.ncbi.nlm.nih.gov/pubmed/32428379/ doi: 10.1111/febs.15369 id: cord-308857-otsrexqu author: Goel, Saurav title: Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic date: 2020-05-28 words: 10608.0 sentences: 526.0 pages: flesch: 47.0 cache: ./cache/cord-308857-otsrexqu.txt txt: ./txt/cord-308857-otsrexqu.txt summary: This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. However, the coronavirus isolated from pangolins is 99% similar in a specific region of the Spike protein, which corresponds to the 74 amino acids involved in the Angiotensin-Converting Enzyme 2 (ACE 2) receptor binding domain, which allows the virus to enter human cells to infect them as shown in Figure 2 (b). (figures reprinted with permission) Our nasal lining tissue contains a rich number of cell receptors called angiotensinconverting enzyme 2 (ACE2), which are favourable sites for the SARS CoV-2 to attach its spiked protein to, thus paving way for the entrance of the virus inside the body. abstract: The world is witnessing tumultuous times as major economic powers including the US, UK, Russia, India, and most of Europe continue to be in a state of lockdown. The worst-hit sectors due to this lockdown are sales, production (manufacturing), transport (aerospace and automotive) and tourism. Lockdowns became necessary as a preventive measure to avoid the spread of the contagious and infectious “Coronavirus Disease 2019” (COVID-19). This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. We also offer perspectives on future considerations on climate change, outsourced versus indigenous manufacturing, automation, and antimicrobial resistance. Overall, this paper attempts to identify key areas where manufacturing can be employed to address societal challenges such as COVID-19. url: https://www.sciencedirect.com/science/article/pii/S2468519420300604?v=s5 doi: 10.1016/j.mtchem.2020.100300 id: cord-351011-v4zmksio author: Golden, Joseph W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 words: 4650.0 sentences: 268.0 pages: flesch: 52.0 cache: ./cache/cord-351011-v4zmksio.txt txt: ./txt/cord-351011-v4zmksio.txt summary: In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. In comparison with the normal lung architecture in uninfected control animals, infected mice necropsied on day 3, and those succumbing to disease on days 5-11, had varying levels of lung injury including area of lung consolidation characterized by inflammation/expansion of 145 alveolar septa with fibrin, edema and mononuclear leukocytes and infiltration of vessel walls by numerous mononuclear leukocytes (Fig 3A, Fig S4, and Table S1 ). Importantly, in our study some animals at the lower dose survived infection despite significant Infection of K18-hACE2 mice by SARS-CoV-2 produces a disease similar to that observed in acute human cases, with development of an acute lung injury associated with edema, production 285 of inflammatory cytokines and the accumulation of mononuclear cells in the lung. abstract: The emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs. url: https://doi.org/10.1101/2020.07.09.195230 doi: 10.1101/2020.07.09.195230 id: cord-304479-uxp1kg86 author: Goodarzi, Pedram title: Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments date: 2020-08-08 words: 8098.0 sentences: 434.0 pages: flesch: 41.0 cache: ./cache/cord-304479-uxp1kg86.txt txt: ./txt/cord-304479-uxp1kg86.txt summary: Finally, recently, a case report study from Japan shows that orally inhaled ciclesonide alleviates the local inflammation in the lung of patients with COVID-19 pneumonia and inhibits the propagation of the virus by antiviral activity [60] . In the same way, a recent case-report study showed that the adoptive transfer therapy of human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) to a Chinese female patient afflicted with acute COVID19 syndromes improved her laboratory tests and CT images [69] . In vitro evidence of activity against SARS-CoV-2 in infected Vero E6 cells reported with high concentrations of the drug [104, 105, 142] FPV significantly improved the latency to relief for pyrexia and cough [99] FPV in patients with COVID-19 led to decrease of viral load and significant improvement in chest imaging compared with the control arm [98] abstract: The SARS-CoV-2 virus is an etiological agent of pandemic COVID-19, which spreads rapidly worldwide. No proven effective therapies currently exist for this virus, and efforts to develop antiviral strategies for the treatment of COVID-19 are underway. The rapidly increasing understanding of SARS-CoV-2 virology provides a notable number of possible immunological procedures and drug targets. However, gaps remain in our understanding of the pathogenesis of COVID-19. In this review, we describe the latest information in the context of immunological approaches and emerging current antiviral strategies for COVID-19 treatment. url: https://api.elsevier.com/content/article/pii/S1567576920323092 doi: 10.1016/j.intimp.2020.106885 id: cord-263532-q044i7ym author: Goyal, Bhupesh title: Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy date: 2020-05-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: [Image: see text] A new coronavirus (CoV) caused a pandemic named COVID-19, which has become a global health care emergency in the present time. The virus is referred to as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) and has a genome similar (∼82%) to that of the previously known SARS-CoV (SARS coronavirus). An attractive therapeutic target for CoVs is the main protease (M(pro)) or 3-chymotrypsin-like cysteine protease (3CL(pro)), as this enzyme plays a key role in polyprotein processing and is active in a dimeric form. Further, M(pro) is highly conserved among various CoVs, and a mutation in M(pro) is often lethal to the virus. Thus, drugs targeting the M(pro) enzyme significantly reduce the risk of mutation-mediated drug resistance and display broad-spectrum antiviral activity. The combinatorial design of peptide-based inhibitors targeting the dimerization of SARS-CoV M(pro) represents a potential therapeutic strategy. In this regard, we have compiled the literature reports highlighting the effect of mutations and N-terminal deletion of residues of SARS-CoV M(pro) on its dimerization and, thus, catalytic activity. We believe that the present review will stimulate research in this less explored yet quite significant area. The effect of the COVID-19 epidemic and the possibility of future CoV outbreaks strongly emphasize the urgent need for the design and development of potent antiviral agents against CoV infections. url: https://www.ncbi.nlm.nih.gov/pubmed/32402186/ doi: 10.1021/acscombsci.0c00058 id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 words: 5057.0 sentences: 242.0 pages: flesch: 53.0 cache: ./cache/cord-277487-jgbjxgh1.txt txt: ./txt/cord-277487-jgbjxgh1.txt summary: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. abstract: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. url: https://doi.org/10.1101/2020.06.20.159715 doi: 10.1101/2020.06.20.159715 id: cord-353826-owoec2ud author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 words: 5496.0 sentences: 269.0 pages: flesch: 53.0 cache: ./cache/cord-353826-owoec2ud.txt txt: ./txt/cord-353826-owoec2ud.txt summary: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Analysis of SARS-CoV-2 S proteinspecific murine splenocyte responses by IFN-γ ELISpot assay showed no statistically significant difference between the primeonly and prime-boost vaccination regimens, in either strain of mouse (Fig. 1a) . SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 prime-only and prime-boost vaccination regimens in mice and pigs SARS-CoV-2 S protein-specific antibody titres in serum were determined by ELISA using recombinant soluble trimeric S (FL-S) and receptor binding domain (RBD) proteins. Small animal models have variable success in predicting vaccine efficacy in larger animals but are an important To analyse SARS-CoV-2 S-specific T cell responses, all mice were sacrificed on day 49 for isolation of splenocytes and pigs were blood sampled longitudinally to isolate PBMC. abstract: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. url: https://doi.org/10.1038/s41541-020-00221-3 doi: 10.1038/s41541-020-00221-3 id: cord-349659-6drnriun author: Grant, Benjamin D. title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents date: 2020-07-01 words: 3203.0 sentences: 207.0 pages: flesch: 57.0 cache: ./cache/cord-349659-6drnriun.txt txt: ./txt/cord-349659-6drnriun.txt summary: title: SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Toward the Development of Point of Care Tests Using Commercially Available Reagents In this work, we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. 10 Antigen detecting ELISAs were previously developed in 2004 for SARS-CoV-1, with limits of detection of approximately 50 pg/mL and clinical sensitivity as a function of days since onset that was significantly better than the useful time window for the current generation of SARS-CoV-2 serology assays. A dose response curve was generated for the half-strip LFA using two commercially available SARS-CoV-2 nucleocapsid (N) proteins, from Genemedi and Genscript. Analytical Chemistry pubs.acs.org/ac Article and determination of realistic limits of detection for a full strip LFA in multiple sample matrices will help point the way toward the best approach for an antigen detecting LFA for SARS-CoV-2. In this paper, we present a half-strip LFA for the detection of nucleocapsid protein of SARS-CoV-2. abstract: [Image: see text] The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, on the basis of previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only a very small number of antigen-detecting LFAs have been developed. Development of a half-strip LFA is a useful first step in the development of any LFA format. In this work, we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. We have tested this LFA in buffer and measured an LOD of 0.65 ng/mL (95% CI of 0.53 to 0.77 ng/mL) ng/mL with recombinant antigen using an optical reader with sensitivity equivalent to a visual read. Further development, including evaluating the appropriate sample matrix, will be required for this assay approach to be made useful in a point of care setting, though this half-strip LFA may serve as a useful starting point for others developing similar tests. url: https://doi.org/10.1021/acs.analchem.0c01975 doi: 10.1021/acs.analchem.0c01975 id: cord-293852-r72c6584 author: Greco, S. title: Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era date: 2020-10-31 words: 8163.0 sentences: 468.0 pages: flesch: 40.0 cache: ./cache/cord-293852-r72c6584.txt txt: ./txt/cord-293852-r72c6584.txt summary: Different studies found that the values of cardiac Troponins were increased in COVID-19 patients with more severe disease [4, 5, [68] [69] [70] , indicating an association of SARS-CoV-2 with myocardial damage. Moreover, the single-cell RNA-sequencing (scRNAseq) approach has been used to profile the SARS-CoV-2 host-response in the PBMCs of COVID-19 patients, and to comprehensively characterize the immunological changes [124] [125] [126] [127] [128] [129] [130] . However, SARS-CoV-2 infection of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) induced cytotoxic effects and RNA-seq findings highlighted significant transcriptional changes in gene pathways related to cellular metabolism and immune response [131] [132] [133] . This analysis also revealed several host-derived lncRNAs differentially expressed in COVID-19 patient-derived lung tissue, and in SARS-CoV-2 infected epithelial cells, including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and NEAT1 (nuclear-enriched autosomal transcript 1) [151] (Fig. 5) . abstract: COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use. url: https://www.ncbi.nlm.nih.gov/pubmed/33129318/ doi: 10.1186/s12967-020-02582-8 id: cord-294527-fct2y5vn author: Guadarrama-Ortiz, Parménides title: Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations date: 2020-09-04 words: 8820.0 sentences: 441.0 pages: flesch: 37.0 cache: ./cache/cord-294527-fct2y5vn.txt txt: ./txt/cord-294527-fct2y5vn.txt summary: The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this context, SARS-CoV-2 can also cause viral meningitis and encephalitis, as demonstrated by a recent report of a 64-yearold patient with laboratory-confirmed COVID-19 who presented neurologic manifestations during the infection, including lethargy, clonus, and pyramidal signs in the lower limbs as well as stiff neck and Brudzinski sign (76) . Future studies are required to evaluate the serologic features of anti-glycolipid antibodies in patients with COVID-19 to elucidate possible mechanisms underlying the association between SARS-CoV-2 infection and Guillain-Barré syndrome. abstract: The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002–2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host- and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field. url: https://doi.org/10.3389/fneur.2020.01039 doi: 10.3389/fneur.2020.01039 id: cord-325014-n7mnhk2v author: Gujski, Mariusz title: Prevalence of Current and Past SARS-CoV-2 Infections among Police Employees in Poland, June–July 2020 date: 2020-10-11 words: 4892.0 sentences: 254.0 pages: flesch: 49.0 cache: ./cache/cord-325014-n7mnhk2v.txt txt: ./txt/cord-325014-n7mnhk2v.txt summary: As the time window for a positive RT-PCR result is short, serological testing, which provides information about whether a person has been exposed to SARS-CoV-2, may be useful for epidemiological purposes to detect the overall burden of previous infection in a given community. The aim of this study was to determine the prevalence of current and past SARS-CoV-2 infections among police employees, a high-risk population due to their professional duties, during the COVID-19 epidemic. Neither sex (p =0.155) nor other variables listed in Figure 2 were significantly associated with the IgG results ( Figure 2 A logistic regression model predicting a positive anti-SARS-CoV-2 IgM+IgA index was developed (Cox and Snell R Square at 0.015 andNagelkerke R Square at 0.033). After including all variables listed in Figures 1 and 2 along with the number of registered cases and deaths due to COVID-19 (per 10,000 inhabitants), only 4 variables showed a correlation with a positive anti-SARS-CoV-2 IgM+IgA index. abstract: Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine the prevalence of current and past SARS-CoV-2 infections among police employees. Methods: This cross-sectional survey was undertaken among 5082 police employees from Mazowieckie Province, Poland. RT-PCR testing for current SARS-CoV-2 infection and serological tests (ELISA) for the presence of anti-SARS-CoV-2 IgM+IgA and IgG antibodies were performed. Results: All RT-PCR tests were negative. The anti-SARS-CoV-2 IgM+IgA index was positive (>8) in 8.9% of participants, including 11.2% women and 7.7% men (p < 0.001). Equivocal IgM+IgA index (6–8) was found in 9.8% of participants, including 11.9% women and 8.7% men (p < 0.001). The IgG index was positive (>6) in 4.3% and equivocal (4–6) in 13.2% of participants. A higher odds of positive IgM+IgA index was found in women vs. men (OR: 1.742) and police officers vs. civilian employees (OR: 1.411). Participants aged ≥60 years had a higher odds of positive IgG index vs. those aged 20–29 years (OR: 3.309). Daily vaping also increased the odds of positive IgG index (OR: 2.058). Conclusions: The majority of Polish police employees are seronegative for SARS-CoV-2 infection. Vaping and older age (≥60 years) were associated with a higher risk of SARS-CoV-2 infection. url: https://doi.org/10.3390/jcm9103245 doi: 10.3390/jcm9103245 id: cord-338775-gh3a0wuf author: Gulersen, Moti title: Histopathological evaluation of placentas after diagnosis of maternal SARS-CoV-2 infection date: 2020-08-15 words: 2512.0 sentences: 152.0 pages: flesch: 44.0 cache: ./cache/cord-338775-gh3a0wuf.txt txt: ./txt/cord-338775-gh3a0wuf.txt summary: Study Design Retrospective cohort study of women diagnosed with SARS-CoV-2 infection who delivered at a single center from April 9th to April 27th, 2020, and had placental specimens reviewed by pathology. Histopathological characteristics were evaluated in each placenta and the incidence of these findings were compared between placentas after diagnosis of maternal SARS-CoV-2 infection and historical controls, as well as between placentas from patients with or without typical symptoms related to infection. Conclusions Based on our data, there are no significant placental histopathological changes that occur after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared to a gestational age-matched historical control group. The results of our study did not demonstrate significant placental histopathological changes 229 occurring after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared 230 to a gestational-age-matched historical control group with a similar incidence of antepartum or Pathology for examination or due to history of melanoma. abstract: Abstract Background The impact of maternal SARS-CoV-2 infection on placental histopathology is not well known. Objectives To determine if significant placental histopathological changes occur after diagnosis of SARS-CoV-2 infection in pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with infection. Study Design Retrospective cohort study of women diagnosed with SARS-CoV-2 infection who delivered at a single center from April 9th to April 27th, 2020, and had placental specimens reviewed by pathology. Women with singleton gestations and laboratory-confirmed SARS-CoV-2 infection were eligible for inclusion. Historical controls selected from a cohort of women who delivered 6 months prior to the study period were matched in a 1:1 fashion by week of gestation at delivery. Histopathological characteristics were evaluated in each placenta and the incidence of these findings were compared between placentas after diagnosis of maternal SARS-CoV-2 infection and historical controls, as well as between placentas from patients with or without typical symptoms related to infection. Statistical analysis included use of Wilcoxon rank sum test and Fisher’s exact test for comparison of categorical and continuous variables. Statistical significance was defined as P value < 0.05. Results A total of 50 placentas after diagnosis of maternal SARS-CoV-2 infection and 50 historical controls were analyzed. Among placentas from patients diagnosed with SARS-CoV-2 infection, 3 (6%) were preterm (33 3/7, 34 6/7 and 36 6/7 weeks of gestation), 16 (32%) were from patients with typical symptoms related to infection and 34 (68%) were from patients without typical symptoms related to the infection. All patients had diagnosis of SARS-CoV-2 infection in the third trimester. Decidual vasculopathy was not visualized in any of the placentas from patients diagnosed with SARS-CoV-2 infection. There was no statistically significant difference in placental histopathological characteristics between the groups. SARS-CoV-2 testing for all neonates at 24 hours of life was negative. Conclusions Based on our data, there are no significant placental histopathological changes that occur after diagnosis of SARS-CoV-2 infection in the third trimester of pregnancy compared to a gestational age-matched historical control group. Similar incidences of histopathological findings were also discovered when comparing placentas from patients with SARS-CoV-2 infection with or without the presence of symptoms typically related to infection. url: https://www.sciencedirect.com/science/article/pii/S2589933320301798?v=s5 doi: 10.1016/j.ajogmf.2020.100211 id: cord-346987-fbqqf00i author: Guo, Yongwen title: Controls of SARS-CoV-2 transmission in orthodontic practice date: 2020-06-05 words: 4660.0 sentences: 244.0 pages: flesch: 47.0 cache: ./cache/cord-346987-fbqqf00i.txt txt: ./txt/cord-346987-fbqqf00i.txt summary: ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. What''s more, the close contact between dental staffs and patients as well as the droplets and aerosols generated during treatment containing saliva and blood further increase the risk of SARS-CoV-2 transmission in dental practice 5 . We must constantly bear in mind that the threat of infection is not visible which poses a challenge on the orthodontic practice thus effective control measures should be taken to prevent the transmission of SARS-CoV-2 and protect both practitioners and patients from the COVID-19. abstract: ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. The SARS-CoV-2 is mainly transmitted through respiratory droplets and close contact. There are also evidences of transmission through aerosols and digestive tracts. Since orthodontic treatment involves large population who need routine return-visits, it was significantly affected and suspended because of the COVID-19 pandemic and the shutdown of the dental clinics and hospitals. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. This is due to the asymptomatic carriers of SARS-CoV-2 or patients in the incubation period may cause the cross infection between orthodontic practitioners and patients. The close proximity between the practitioners and the patients, and the generation of droplets and aerosols that contain saliva and blood during treatment further increase the risks of transmission. In this review, we summarized the preventive strategies for controls of SARS-CoV-2 transmission to protect both staffs and patients during the orthodontic practice. url: https://doi.org/10.1016/j.ajodo.2020.05.006 doi: 10.1016/j.ajodo.2020.05.006 id: cord-265128-i0d4lxko author: Gurung, Arun Bahadur title: Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach date: 2020-05-22 words: 2234.0 sentences: 168.0 pages: flesch: 57.0 cache: ./cache/cord-265128-i0d4lxko.txt txt: ./txt/cord-265128-i0d4lxko.txt summary: Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Structure-based drug design primarily relies on molecular docking to identify lead molecules against the target proteins from chemical libraries [12, 13] . The natural products such as traditional medicines and plant-derived compounds (phytochemicals) are the rich sources of promising antiviral drugs [14] . The binding energies and inhibition constants of the phytochemicals with the SARS-CoV-2 M pro enzyme were compared with that of a set of twelve FDA approved antiviral drugs-a) Viral abstract: A new SARS coronavirus (SARS-CoV-2) belonging to the genus Betacoronavirus has caused a pandemic known as COVID-19. Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. There are no human proteases with similar cleavage specificity and therefore, inhibitors are highly likely to be nontoxic. Therefore, targeting the SARS-CoV-2 M(pro) enzyme with small molecules can block viral replication. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Bonducellpin D was identified as the best lead molecule which shows higher binding affinity (−9.28 kcal/mol) as compared to the control (−8.24 kcal/mol). The molecular binding was stabilized through four hydrogen bonds with Glu166 and Thr190 as well as hydrophobic interactions via eight residues. The SARS-CoV-2 M(pro) shows identities of 96.08% and 50.65% to that of SARS-CoV M(pro) and MERS-CoV M(pro) respectively at the sequence level. At the structural level, the root mean square deviation (RMSD) between SARS-CoV-2 M(pro) and SARS-CoV M(pro) was found to be 0.517 Å and 0.817 Å between SARS-CoV-2 M(pro) and MERS-CoV M(pro). Bonducellpin D exhibited broad-spectrum inhibition potential against SARS-CoV M(pro) and MERS-CoV M(pro) and therefore is a promising drug candidate, which needs further validations through in vitro and in vivo studies. url: https://doi.org/10.1016/j.lfs.2020.117831 doi: 10.1016/j.lfs.2020.117831 id: cord-348696-86nbwon2 author: Güemes-Villahoz, Noemi title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review date: 2020-08-18 words: 4199.0 sentences: 216.0 pages: flesch: 43.0 cache: ./cache/cord-348696-86nbwon2.txt txt: ./txt/cord-348696-86nbwon2.txt summary: title: Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review A multicenter study which documented potential risk factors for SARS-CoV-2 transmission in patients requiring intubation [7] reported that unprotected eye contact with secretions from infected patients was the most predictive variable for transmission to healthcare workers. A recent study evaluated the ocular tropism of SARS-CoV-2 in patients with confirmed COVID-19. Of the 56 subjects investigated there was only one patient who gave a history of prior pterygium surgery, with conjunctivitis and a positive PCR result from the conjunctival swab highlighting the importance of an intact ocular surface in resisting virus invasion [25] . Despite ocular complications not being a common clinically detectable manifestation of SARS-CoV-2 infection, recent evidence suggests that ocular exposure may represent a major transmission route for the virus. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection SARS-CoV-2 RNA detection in tears and conjunctival secretions of COVID-19 patients with conjunctivitis abstract: SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread. url: https://doi.org/10.1007/s12325-020-01442-7 doi: 10.1007/s12325-020-01442-7 id: cord-281529-2rec51xg author: Haagmans, Bart L title: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation date: 2013-12-17 words: 4032.0 sentences: 205.0 pages: flesch: 57.0 cache: ./cache/cord-281529-2rec51xg.txt txt: ./txt/cord-281529-2rec51xg.txt summary: We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. 13 Both MERS-CoV spike protein binding antibodies and virus neutralising antibodies were reported in dromedary camels from diff erent regions, including Oman and Egypt, but no virus shedding could be detected and, therefore, the signifi cance of these observations remained an issue of debate. The camel MERS-CoV clustered with viral sequences obtained from the two human cases related to the farm and with a sequence from Hafr-Al-Batin as the next closest relative (fi gure 1). However, virological testing was unable to detect MERS-CoV viral sequences in camels, probably because only faecal and serum samples were analysed. Our report describes the fi rst detection of MERS-CoV in dromedary camels on a farm in Qatar that had been linked to human cases of the disease. abstract: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. METHODS: We took nose swabs, rectal swabs, and blood samples from all camels on the Qatari farm. We tested swabs with RT-PCR, with amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific PCRs and obtained sequences were used for phylogentic analysis together with sequences from the linked human cases and other human cases. We tested serum samples from the camels for IgG immunofluorescence assay, protein microarray, and virus neutralisation assay. FINDINGS: We obtained samples from 14 camels on Oct 17, 2013. We detected MERS-CoV in nose swabs from three camels by three independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment (940 nucleotides) and a 4·2 kb concatenated fragment were very similar to the MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr-Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs, but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding antibodies that correlated well with the presence of neutralising antibodies to MERS-CoV. INTERPRETATION: Our study provides virological confirmation of MERS-CoV in camels and suggests a recent outbreak affecting both human beings and camels. We cannot conclude whether the people on the farm were infected by the camels or vice versa, or if a third source was responsible. FUNDING: European Union projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and the VIRGO consortium. url: https://www.ncbi.nlm.nih.gov/pubmed/24355866/ doi: 10.1016/s1473-3099(13)70690-x id: cord-351649-87g7g5au author: Haagmans, Bart L. title: SARS date: 2009-01-30 words: 6736.0 sentences: 298.0 pages: flesch: 40.0 cache: ./cache/cord-351649-87g7g5au.txt txt: ./txt/cord-351649-87g7g5au.txt summary: Because the disease in macaques caused by SARS-CoV infection was pathologically similar to that seen in human patients with SARS, and since the virus should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. African green monkeys immunized via the respiratory tract with two doses of a recombinant Newcastle disease virus encoding the S protein developed a relatively high titer of SARS-CoV neutralizing antibodies and upon challenge demonstrated a 1000-fold zoonotic coronaviruses. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies abstract: Abstract Five years after the first severe acute respiratory syndrome (SARS) outbreak, several candidate SARS-coronavirus (CoV) vaccines are at various stages of preclinical and clinical development. Based on the observation that SARSCoV infection is efficiently controlled upon passive transfer of antibodies directed against the spike (S) protein of SARS-CoV, vaccines containing the S protein have been formulated. Animals immunized with inactivated whole virus vaccines or live-recombinant vaccines expressing the SARS-CoV S protein (e.g., using rabies virus, vesicular stomatitis virus, bovine parainfluenza virus type 3, adenovirus, or attenuated vaccinia virus MVA as a vector), as well as mice immunized with DNA vaccines expressing the S protein gene all developed neutralizing antibodies to SARS-CoV and were protected against SARS-CoV challenge. Although much effort has been focused on developing a SARS vaccine, the commercial viability of such a vaccine for SARS-CoV will ultimately depend on whether the virus re-emerges in the near future. This vaccine should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. Given the fact that in the previous outbreak mainly the elderly succumbed to the infection, special attention should be given to vaccines that are able to efficiently protect aged individuals. url: https://api.elsevier.com/content/article/pii/B9780123694089000366 doi: 10.1016/b978-0-12-369408-9.00036-6 id: cord-341234-2zgfcrwc author: Hallak, Jorge title: Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil date: 2020-09-02 words: 3614.0 sentences: 178.0 pages: flesch: 41.0 cache: ./cache/cord-341234-2zgfcrwc.txt txt: ./txt/cord-341234-2zgfcrwc.txt summary: title: Concise practice recommendations for the provision of andrological services and assisted reproductive technology for male infertility patients during the SARS-CoV-2 in Brazil Recently, a group of 27 experts from 15 countries and five continents has argued that postponing andrological services and male infertility care during the COVID-19 pandemic could permanently compromise the prospects of biological parenthood for ''time-sensitive'' patients, thus resulting in a devastating psychological impact on men undergoing fertility-related treatment (1) . A recent probabilistic pilot study conducted in seven districts of the city of São Paulo to estimate the prevalence of herd immunity showed that about 5.2% individuals had SARS-CoV-2 IgG antibodies, corresponding to an overall infection rate We reiterate that andrological services and male infertility care cannot be considered low priority during the current SARS-CoV-2 pandemic, particularly for the most vulnerable patients, like those with cancer, patients using immunosuppressive therapy, and the azoospermic/cryptozoospermic men under medical or post-surgical treatment to improve spermatogenesis. abstract: nan url: https://doi.org/10.1590/s1677-5538.ibju.2020.06.03 doi: 10.1590/s1677-5538.ibju.2020.06.03 id: cord-268206-ino9srb6 author: Hamed, Manal A. title: An overview on COVID-19: reality and expectation date: 2020-06-01 words: 6067.0 sentences: 330.0 pages: flesch: 46.0 cache: ./cache/cord-268206-ino9srb6.txt txt: ./txt/cord-268206-ino9srb6.txt summary: Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. In the current SARS-COV-2 pandemic, Wu and McGoogan (2020) showed that patients with chronic diseases, including diabetes, were at higher risk for severe COVID-19 infection and mortality. The former (S) is the wild type which is milder while the latter (L) is the novel one which resulted in high binding affinity between SARS-COV-2 virus with angiotensin-converting enzyme 2 receptor in human cells. The use of convalescent plasma was recommended before as an important treatment during outbreaks of Ebola virus, Middle East respiratory syndrome coronavirus, SARS-COV-1, H5N1 avian influenza, and H1N1 influenza (Zhou et al. In a study involving patients with pandemic influenza (H1N1) and SARS virus, treatment of severe infection with convalescent plasma was associated with reduced respiratory viral load, serum cytokine response, and mortality (Cheng et al. abstract: Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO’s strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions. url: https://doi.org/10.1186/s42269-020-00341-9 doi: 10.1186/s42269-020-00341-9 id: cord-294136-e69ao8j0 author: Han, Dongsheng title: COVID-19: Insight into the asymptomatic SARS-COV-2 infection and transmission date: 2020-08-27 words: 5215.0 sentences: 263.0 pages: flesch: 42.0 cache: ./cache/cord-294136-e69ao8j0.txt txt: ./txt/cord-294136-e69ao8j0.txt summary: successfully isolated SARS-CoV-2 from throat swabs of two asymptomatic patients in a cell culture of Caco-2 cells, suggesting the potential for presymptomatic transmission [16] ; (5) Increasing studies show clear epidemiological evidence of human-to-human asymptomatic spread of COVID-19 (described in the following section); (6) Asymptomatic infection tends to be, but is not only, identified among young people (<20 years old) [14, 15, [17] [18] [19] ; And (7) the majority (>90%) of asymptomatic patients appears to have a milder clinical course during hospitalization [15] , but the severity of the symptoms of the secondary patients infected by SARS-COV-2 from asymptomatic patients varies based on their physical constitution [2, 20] . As the transmission of SARS-COV-2 may occur in the early course of infection and a high viral load in respiratory samples could be detected [13] , RT-PCR testing for this virus is more suitable for screening at earlier stages of infection in key populations, such as patients with obvious symptoms and close contacts of asymptomatic patients [35] . abstract: The existence of a substantial but unclear number of asymptomatic SARS-COV-2 patients worldwide has raised concerns among global public health authorities. In this review, according to the published literature, we provided the evidence that asymptomatic infections can result in person-to-person transmission. Four studies suggested that the virus can be transmitted by asymptomatic patients for at least two consecutive generations, indicating its strong infectivity. Asymptomatic infection tends to be, but is not only, identified among young people (<20 years old). The majority of asymptomatic patients appear to have a milder clinical course during hospitalization, but the severity of the symptoms of the secondary patients infected by SARS-COV-2 from asymptomatic patients varies with their physical constitution. The proportion of asymptomatic individuals among all confirmed cases widely differed (from 1.95% to 87.9%) according to the study setting and the populations studied. The increasing large-scale tests are expected to give more information about the true number of asymptomatic infections in the population. In China and other countries, various guidelines for management of asymptomatic cases have been issued. Importantly, early detection, early reporting, early isolation and early treatment of asymptomatic patients require the joint efforts of policy makers, clinicians, technicians, epidemiologists, virologists and patients. url: https://doi.org/10.7150/ijbs.48991 doi: 10.7150/ijbs.48991 id: cord-297941-7yut9vt4 author: Haq, M. title: Seroprevalence and Risk Factors of SARS CoV-2 in Health Care Workers of Tertiary-Care Hospitals in the Province of Khyber Pakhtunkhwa, Pakistan date: 2020-09-30 words: 2709.0 sentences: 210.0 pages: flesch: 61.0 cache: ./cache/cord-297941-7yut9vt4.txt txt: ./txt/cord-297941-7yut9vt4.txt summary: In the recent past many studies from the developed countries have been published on the prevalence of SARS CoV2 antibodies and the risk factors of COVID 19 in healthcare-workers but little is known from developing countries. Methods: This cross-sectional study was conducted on prevalence of SARS CoV2 antibody and risk factors for seropositivity in HCWs in tertiary care hospitals of Peshawar city, Khyber Pakhtunkhwa province Pakistan. To our knowledge this is the first study of assessing SARS-CoV-2 antibodies of HCWs form both public and private tertiary care hospitals in Peshawar, Pakistan. To our knowledge this is the first study on prevalence of SARS CoV-2 antibodies in HCW of tertiary care hospitals in Pakistan. The risk of becoming positive for SARS-CoV-2 antibodies did not increase with history of direct contact with COVID patients within or outside the hospital. abstract: Background: High number of SARS CoV2 infected patients has overburdened healthcare delivery system, particularly in low-income countries. In the recent past many studies from the developed countries have been published on the prevalence of SARS CoV2 antibodies and the risk factors of COVID 19 in healthcare-workers but little is known from developing countries. Methods: This cross-sectional study was conducted on prevalence of SARS CoV2 antibody and risk factors for seropositivity in HCWs in tertiary care hospitals of Peshawar city, Khyber Pakhtunkhwa province Pakistan. Findings: The overall seroprevalence of SARS CoV2 antibodies was 30.7% (CI, 27.8 to 33.6) in 1011 HCWs. Laboratory technicians had the highest seropositivity (50.0%, CI, 31.8 to 68.1). Risk analysis revealed that wearing face-mask and observing social-distancing within a family could reduce the risk (OR:0.67. p<0.05) and (OR:0.73. p<0.05) while the odds of seropositivity were higher among those attending funeral and visiting local-markets (OR:1.83. p<0.05) and (OR:1.66. p<0.01). In Univariable analysis, being a nursing staff and a paramedical staff led to higher risk of seropositivity (OR:1.58. p< 0.05), (OR:1.79. p< 0.05). Fever (OR:2.36, CI, 1.52 to 3.68) and loss of smell (OR:2.95, CI: 1.46 to 5.98) were significantly associated with increased risk of seropositivity (p<0.01). Among the seropositive HCWs, 165 (53.2%) had no symptoms at all while 145 (46.8%) had one or more symptoms. Interpretation: The high prevalence of SARS CoV2 antibodies in HCWs warrants for better training and use of protective measure to reduce their risk. Early detection of asymptomatic HCWs may be of special importance because they are likely to be potential threat to others during the active phase of viremia. Funding: Prime Foundation Pakistan. url: https://doi.org/10.1101/2020.09.29.20203125 doi: 10.1101/2020.09.29.20203125 id: cord-299093-zp07aqpm author: Harrison, Andrew G. title: Mechanisms of SARS-CoV-2 transmission and pathogenesis date: 2020-10-14 words: 6389.0 sentences: 385.0 pages: flesch: 46.0 cache: ./cache/cord-299093-zp07aqpm.txt txt: ./txt/cord-299093-zp07aqpm.txt summary: Thus, evasion of IFN signaling by SARS-CoV-2 and impaired IFN production in J o u r n a l P r e -p r o o f human peripheral blood immune cells might contribute to the productive viral replication, transmission, and severe pathogenesis during COVID-19, although further testing is warranted to fully dissect these putative evasion pathways [95] . For instance, Krt18-hACE2 and betaactin-hACE2-transgenic mice rapidly succumb to SARS-CoV-2 infection with lung infiltration of inflammatory immune cells inducing severe pulmonary disease, accompanied by evident thrombosis and anosmia, which partially recapitulate human COVID-19 [114] [115] . Furthermore, upon viral challenge, lymphocytes have expanded in rhesus macaque models around 5 dpi with complementary B-cell responses against SARS-CoV-2 Spike appearing 10-15 dpi in blood samples [125] ; expansion of these adaptive immune compartments was analogous to those observed in COVID-19 patients [37, 125, [132] [133] [134] . abstract: The emergence of SARS-coronavirus 2 (SARS-CoV-2) marks the third highly pathogenic coronavirus to spill over into the human population. SARS-CoV-2 is highly transmissible with a broad tissue tropism that is likely perpetuating the pandemic. However, important questions remain regarding its transmissibility and pathogenesis. In this review, we summarize current SARS-CoV-2 research, with an emphasis on transmission, tissue tropism, viral pathogenesis, and immune antagonism. We further present advances in animal models that are important for understanding the pathogenesis of SARS-CoV-2, vaccine development, and therapeutic testing. When necessary, comparisons are made from studies with SARS to provide further perspectives on COVID-19, as well as draw inferences for future investigations. url: https://www.ncbi.nlm.nih.gov/pubmed/33132005/ doi: 10.1016/j.it.2020.10.004 id: cord-297786-jz1d1m2e author: Hasan, Md. Mahbub title: Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date: 2020-08-26 words: 3271.0 sentences: 187.0 pages: flesch: 54.0 cache: ./cache/cord-297786-jz1d1m2e.txt txt: ./txt/cord-297786-jz1d1m2e.txt summary: Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Then, we studied the variants present in different isolates of Bangladesh to investigate the pattern of mutations, identify UMs, and discuss the pseudo-effect of these mutations on the structure and function of encoded proteins, with their role in pathogenicity. To understand the SARS-CoV-2 viral transmission in Bangladesh, we performed phylogenetic analysis on the selected 207 viral genomes reported from different districts of Bangladesh along with selected 467 globally submitted sequences as reported from 42 countries and 6 continents ( Figure 1 ). abstract: Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. Nearly 0.4 million mutations were identified so far in ∼60,000 SARS-CoV-2 genomic sequences. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Phylogenetic analyses indicates that in Bangladesh, SARS-CoV-2 viruses might arrived through infected travelers from European countries, and the GR clade was found as predominant in this region. We found 2602 mutations including 1602 missense mutations, 612 synonymous mutations, 36 insertions and deletions with 352 other mutations types. In line with the global trend, D614G mutation in spike glycoprotein was predominantly high (95.6%) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab, S, ORF3a, M and N of genomes, having nucleotide shift at G614 (n=459), were significantly higher (p≤0.001) than those having mutation at D614 (n=215). Previously reported frequent mutations such as P4715L, D614G, R203K, G204R and I300F were also prevalent in Bangladeshi isolates. Additionally, 87 unique amino acid changes were revealed and were categorized as originating from different cities of Bangladesh. The analyses would increase our understanding of variations in virus genomes circulating in Bangladesh and elsewhere and help develop novel therapeutic targets against SARS-CoV-2. url: https://doi.org/10.1101/2020.08.25.267658 doi: 10.1101/2020.08.25.267658 id: cord-333547-88dkh6xd author: Hasan, Shadi W. title: Detection and Quantification of SARS-CoV-2 RNA in Wastewater and Treated Effluents: Surveillance of COVID-19 Epidemic in the United Arab Emirates date: 2020-10-19 words: 3980.0 sentences: 220.0 pages: flesch: 54.0 cache: ./cache/cord-333547-88dkh6xd.txt txt: ./txt/cord-333547-88dkh6xd.txt summary: Testing SARS-CoV-2 viral loads in wastewater has recently emerged as a method of tracking the prevalence of the virus and an early-warning tool for predicting outbreaks in the future. A limited number of studies have shown that the shedding period of SARS-CoV-2 in stool samples varies considerably, and can still be detected up to 27.9 ± 10.7 days after infection in some cases [9, 11] . Consequently, the main objectives of this study were: (i) to detect the presence of SARS-CoV-2 virus in municipal (untreated) wastewater and treated effluents of wastewater treatment plants (WWTPs) in the UAE; (ii) to quantify the viral concentration in viral gene copies per liter; and (iii) to explore whether these measurements mirror infections in the population in order to comment on the utility of this method to track the epidemiology of the disease. abstract: Testing SARS-CoV-2 viral loads in wastewater has recently emerged as a method of tracking the prevalence of the virus and an early-warning tool for predicting outbreaks in the future. This study reports SARS-CoV-2 viral load in wastewater influents and treated effluents of 11 wastewater treatment plants (WWTPs), as well as untreated wastewater from 38 various locations, in the United Arab Emirates (UAE) in May and June 2020. Composite samples collected over twenty-four hours were thermally deactivated for safety, followed by viral concentration using ultrafiltration, RNA extraction using commercially available kits, and viral quantification using RT-qPCR. Furthermore, estimates of the prevalence of SARS-CoV-2 infection in different regions were simulated using Monte Carlo. Results showed that the viral load in wastewater influents from these WWTPs ranged from 7.50E+02 to over 3.40E+04 viral gene copies/L with some plants having no detectable viral RNA by RT-qPCR. The virus was also detected in 85% of untreated wastewater samples taken from different locations across the country, with viral loads in positive samples ranging between 2.86E+02 and over 2.90E+04 gene copies/L. It was also observed that the precautionary measures implemented by the UAE government correlated with a drop in the measured viral load in wastewater samples, which were in line with the reduction of COVID-19 cases reported in the population. Importantly, none of the 11 WWTPs’ effluents tested positive during the entire sampling period, indicating that the treatment technologies used in the UAE are efficient in degrading SARS-CoV-2, and confirming the safety of treated re-used water in the country. SARS-CoV-2 wastewater testing has the potential to aid in monitoring or predicting an outbreak location and can shed light on the extent viral spread at the community level. url: https://doi.org/10.1016/j.scitotenv.2020.142929 doi: 10.1016/j.scitotenv.2020.142929 id: cord-275138-033r259v author: Hayden, Frederick G title: Towards improving clinical management of Middle East respiratory syndrome coronavirus infection date: 2014-07-31 words: 1624.0 sentences: 78.0 pages: flesch: 38.0 cache: ./cache/cord-275138-033r259v.txt txt: ./txt/cord-275138-033r259v.txt summary: Many agents have inhibitory activity in vitro for coronaviruses, including some licensed drugs, 7-9 but it is unclear whether their human pharmacology and tolerability would enable suffi cient doses to be given to exert antiviral eff ects in patients with MERS-CoV. 4 Ribavirin and interferon combinations are associated with modest Centre For Infections/Public Health England/Science Photo Library antiviral eff ects in MERS-CoV inoculated rhesus macaques given high doses. 7 For MERS-CoV, low neutralising antibody responses and inability to acquire suffi cient convalescent plasma from survivors with comorbidities might restrict the eff ectiveness of this treatment, although these limitations might not apply to infected health-care workers. With support as needed from international partners like WHO and ISARIC, 11 regional governments, and funders, Middle Eastern colleagues have both the opportunity and the responsibility to undertake studies to advance the understanding of eff ective prevention and treatment strategies for MERS-CoV and any future novel CoV outbreaks. abstract: nan url: https://doi.org/10.1016/s1473-3099(14)70793-5 doi: 10.1016/s1473-3099(14)70793-5 id: cord-301693-3hsu2u1k author: He, Yuwen title: Value of Viral Nucleic Acid in Sputum and Feces and Specific IgM/IgG in Serum for the Diagnosis of Coronavirus Disease 2019 date: 2020-08-06 words: 3551.0 sentences: 184.0 pages: flesch: 53.0 cache: ./cache/cord-301693-3hsu2u1k.txt txt: ./txt/cord-301693-3hsu2u1k.txt summary: To improve the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we analyzed the results of viral nucleic acid and serum-specific antibody tests on clinical samples from 20 patients with SARS-CoV-2 infection diagnosed at the First Affiliated Hospital of Guangzhou Medical University in China. By comparing various sample types collected from COVID-19 patients, we revealed multiple pathways for SARS-CoV-2 shedding, and a prolonged detectable period for viral nucleic acid test in sputum specimens, demonstrating that the timeline of the viral shedding is of great value in determining the time of release from quarantine or discharge from hospital. We undertook a study on the viral nucleic acids of SARS-CoV-2 in swabs (nasal, pharyngeal), sputum and feces, as well as antibodies in the serum of COVID-19 patients admitted to the First Affiliated Hospital of Guangzhou Medical University, China. abstract: A new type of coronavirus-induced pneumonia eventually termed “coronavirus disease 2019” (COVID-19) was diagnosed in patients in Wuhan (Hubei Province, China) in December 2019, and soon spread worldwide. To improve the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we analyzed the results of viral nucleic acid and serum-specific antibody tests on clinical samples from 20 patients with SARS-CoV-2 infection diagnosed at the First Affiliated Hospital of Guangzhou Medical University in China. By comparing various sample types collected from COVID-19 patients, we revealed multiple pathways for SARS-CoV-2 shedding, and a prolonged detectable period for viral nucleic acid test in sputum specimens, demonstrating that the timeline of the viral shedding is of great value in determining the time of release from quarantine or discharge from hospital. We also recommend for the application of serological test to assist in confirming SARS-CoV-2 infection judged by viral nucleic acid test, especially when COVID-19-related symptoms have appeared and the viral nucleic acid test was negative. Our findings are critical for the diagnosis of SARS-CoV-2 infection and for determining deadline of restriction measures to prevent transmission caused by convalescent patients with COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32850506/ doi: 10.3389/fcimb.2020.00445 id: cord-032751-pmclolvh author: Head, Katharine J. title: A National Survey Assessing SARS-CoV-2 Vaccination Intentions: Implications for Future Public Health Communication Efforts date: 2020-09-23 words: 5086.0 sentences: 305.0 pages: flesch: 48.0 cache: ./cache/cord-032751-pmclolvh.txt txt: ./txt/cord-032751-pmclolvh.txt summary: Research Question 2: What are the SARS-CoV-2 vaccine behavioral intentions of adults in the U.S. when a health care provider recommends the vaccine? Importantly, because vaccine intent and/or need may be different for people who were previously infected with SARS-CoV-2 and perceived threat variables (discussed below) are usually only measured for future threats, only participants who answered "no" to the question "do you believe that you''ve had COVID-19" are included in the current study (n = 3,159). Step 3 of the hierarchical regression model, with all variables included, less education was associated with lower intent to receive a SARS-CoV-2 vaccine. The health belief variables that were significant in the full regression model were all positively associated with intent to receive a SARS-CoV-2 vaccine. abstract: With SARS-CoV-2 vaccines under development, research is needed to assess intention to vaccinate. We conducted a survey (N = 3,159) with U.S. adults in May 2020 assessing SARS-CoV-2 vaccine intentions, intentions with a provider recommendation, and sociodemographic and psychosocial variables. Participants had high SARS-CoV-2 vaccine intentions (M = 5.23/7-point scale), which increased significantly with a provider recommendation (M = 5.47). Hierarchical linear regression showed that less education and working in health care were associated with lower intent, and liberal political views, altruism, and COVID-19-related health beliefs were associated with higher intent. This work can inform interventions to increase vaccine uptake, ultimately reducing COVID-19-related morbidity and mortality. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520657/ doi: 10.1177/1075547020960463 id: cord-337712-ylqgraos author: Heinz, Franz X. title: Profile of SARS-CoV-2 date: 2020-10-30 words: 6028.0 sentences: 301.0 pages: flesch: 44.0 cache: ./cache/cord-337712-ylqgraos.txt txt: ./txt/cord-337712-ylqgraos.txt summary: Despite these similarities, distinguishing features were identified that are likely to contribute to the biological differences observed between the two viruses, including the significantly higher rate of subclinical and mild infections caused by SARS-CoV-2, which makes control of virus spread currently so difficult. If expectations were too optimistic and results obtained with some of the front runners are disappointing, windows of opportunity will open for an arsenal of alternative developments in progress [54, 59] (https:// www.who.int/publications/m/item/draft-landscapeof-covid-19-candidate-vaccines, accessed 2 October 2020) These include subunit vaccines with S proteins stabilized in their prefusion conformation in combination with potent adjuvants, use of the RBD only as an immunogen instead of the whole S protein [67, 68] , other rationally designed immunogens [69] , other (non-Adeno) vector vaccines including replication-competent vectors [55, 70] , self-amplifying RNA vaccines [71] , live-attenuated vaccines [55] , DNA vaccines [72] , and intranasally applied vaccines with the potential to induce local immunity at the site of virus entry [73] . abstract: The recent emergence of a new coronavirus (severe acute respiratory syndrome coronavirus‑2, SARS-CoV-2) that is transmitted efficiently among humans and can result in serious disease and/or death has become a global threat to public health and economy. In this article, we describe some of the most important characteristics of this new virus (including gaps in our understanding) and provide a perspective of ongoing activities for developing virus-specific countermeasures, such as vaccines and antiviral drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/33125580/ doi: 10.1007/s00508-020-01763-1 id: cord-286298-pn9nwl64 author: Helmy, Yosra A. title: The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control date: 2020-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global increases in the number of cases daily. Therefore, the WHO has declared COVID-19 a pandemic. The disease is characterized by fever, dry cough, and chest pain with pneumonia in severe cases. In the beginning, the world public health authorities tried to eradicate the disease in China through quarantine but are now transitioning to prevention strategies worldwide to delay its spread. To date, there are no available vaccines or specific therapeutic drugs to treat the virus. There are many knowledge gaps about the newly emerged SARS-CoV-2, leading to misinformation. Therefore, in this review, we provide recent information about the COVID-19 pandemic. This review also provides insights for the control of pathogenic infections in humans such as SARS-CoV-2 infection and future spillovers. url: https://www.ncbi.nlm.nih.gov/pubmed/32344679/ doi: 10.3390/jcm9041225 id: cord-252456-971d0sir author: Hemida, Maged Gomaa title: The SARS-CoV-2 outbreak from a one health perspective date: 2020-03-16 words: 4824.0 sentences: 244.0 pages: flesch: 55.0 cache: ./cache/cord-252456-971d0sir.txt txt: ./txt/cord-252456-971d0sir.txt summary: The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. Currently, the case fatality rate is relatively low (⁓3.6%) compared to infections with severe acute respiratory syndrome coronavirus (SARS-CoV, (10%) and MERS-CoV (32%) [11] . Based on the previous emergence history of SARS-CoV, the presence of a large number of mammals and birds overcrowded in one place may give a chance for pathogens, particularly those with RNA genomes such as coronaviruses and influenza viruses, to emerge. Based on the previous experience from the other emerging diseases, particularly SARS-CoV and influenza viruses, avoiding the mixing of various species of animals, birds, and mammals, is highly suggested [51, 65, 66] . The process of decontamination of the virus-contaminated surfaces by the appropriate disinfectants or virucidal agents was successful in case of other respiratory viruses such as SARS-CoV and avian influenza [59] . abstract: The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible. url: https://api.elsevier.com/content/article/pii/S2352771420300185 doi: 10.1016/j.onehlt.2020.100127 id: cord-325902-33pxylb3 author: Hemida, Maged Gomaa title: Middle East Respiratory Syndrome Coronavirus and the One Health concept date: 2019-08-22 words: 6356.0 sentences: 325.0 pages: flesch: 58.0 cache: ./cache/cord-325902-33pxylb3.txt txt: ./txt/cord-325902-33pxylb3.txt summary: This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. Experimental MERS-CoV infection in both alpacas and llamas showed a similar pattern to that of dromedary camels (Crameri et al., 2016; Vergara-Alert et al., 2017) , which suggested that both animals might act as a model animal for the study of MERS-CoV in vivo. Very few studies reported the cross-reactivity between MERS-CoV and other coronaviruses such as the bovine coronavirus (BCoV) that might infect dromedary camels. Dromedary camels remain the amplifier of the virus; the close contact of these animals to the human population in certain regions of Africa and Asia may pose a great risk for human infection and indirectly contribute to the spread of the virus. Lack of middle East respiratory syndrome coronavirus transmission from infected camels abstract: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated. url: https://www.ncbi.nlm.nih.gov/pubmed/31497405/ doi: 10.7717/peerj.7556 id: cord-349262-gnqbyc6t author: Hemida, Maged Gomaa title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) date: 2020-10-14 words: 3172.0 sentences: 174.0 pages: flesch: 62.0 cache: ./cache/cord-349262-gnqbyc6t.txt txt: ./txt/cord-349262-gnqbyc6t.txt summary: title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. However, the nasal swabs are still the sample of choice in the diagnosis of MERS-CoV among the infected dromedary camel population. Detection of the virus in the air of positive camel''s herd [5, 6] may suggest the virus is excreted in the breath of the infected animals in high concentration. The aim of our study was to test the possibility of MERS-CoV shedding in the breath of the infected dromedary camels. Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Dromedary camels and the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) abstract: Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus is released in the secretions of the infected camels, especially the nasal tract. The virus shedding curve through the nasal secretions was studied. Although human transmission of the virus through the respiratory tract of close contact people with dromedary reported previously, the exact mechanism of transmission is still largely unknown. The main goal of this study was to check the possibility of MERS-CoV shedding in the exhaled air of the infected camels. To achieve this goal, we conducted a follow-up study in one of the dromedary camel herds, December 2018–April 2019. We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. Our results showed that some of the tested nasal swabs and breath were positive from 24 March 2019 until 7 April 2019. The phylogenetic analysis of the obtained S and N gene sequences revealed the detected viruses are clustering together with some human and camel samples from the eastern region, especially from Al-Hufuf city, as well as some samples from Qatar and Jordon. These results are clearly showing the possibility of shedding of the virus in the breath of the infected camels. This could explain, at least in part, the mechanism of transmission of MERS-CoV from animals to humans. This study is confirming the shedding of MERS-CoV in the exhaled air of the infected camels. Further studies are needed for a better understanding of the MERS-CoV. url: https://doi.org/10.1017/s0950268820002459 doi: 10.1017/s0950268820002459 id: cord-330597-nftwj0d5 author: Hopfer, Helmut title: Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues date: 2020-09-27 words: 4636.0 sentences: 328.0 pages: flesch: 48.0 cache: ./cache/cord-330597-nftwj0d5.txt txt: ./txt/cord-330597-nftwj0d5.txt summary: Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. To better understand the ultrastructural morphology of SARS-CoV-2 infection and COVID-19, we will first briefly discuss the pathogenesis of COVID-19 and coronavirus replication in general and then examine the TEM findings in more detail. All rights reserved Coronaviruses including SARS-CoV-2 and the morphological changes associated with replication can be visualised by TEM in infected cell lines (figure 3A-G) [81] [82] [83] [84] [85] 87, 88] or organoids [96, 97] . Based on the cell culture findings outlined above, we expect to find the same SARS-CoV-2 morphology and distribution in vesicles of autopsy and biopsy tissues of COVID-19 patients. abstract: Transmission electron microscopy has become a valuable tool to investigate tissues of COVID‐19 patients because it allows visualisation of SARS‐CoV‐2, but the “virus‐like particles” described in several organs have been highly contested. Because most electron microscopists in pathology are not accustomed to analysing viral particles and subcellular structures, our review aims to discuss the ultrastructural changes associated with SARS‐CoV‐2 infection and COVID‐19 with respect to pathology, virology, and electron microscopy. Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. Virions assemble by budding into the endoplasmic reticulum‐Golgi intermediate complex and are characterized by electron dense dots of cross‐sections of the nucleocapsid inside the viral particles. Physiological mimickers such as multivesicular bodies or coated vesicles serve as perfect decoys. Compared to other in‐situ techniques, transmission electron microscopy is the only method to visualize assembled virions in tissues and will be required to prove SARS‐CoV‐2 replication outside the respiratory tract. In practice, documenting in tissues the characteristic features seen in infected cell cultures, seems to be much more difficult than anticipated. In our view, the hunt for coronavirus by transmission electron microscopy is still on. url: https://doi.org/10.1111/his.14264 doi: 10.1111/his.14264 id: cord-350855-gofzhff7 author: Hou, Yixuan J. title: SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract date: 2020-05-27 words: 3416.0 sentences: 222.0 pages: flesch: 50.0 cache: ./cache/cord-350855-gofzhff7.txt txt: ./txt/cord-350855-gofzhff7.txt summary: High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. We measured the relative infectivity of the SARS-CoV-2 GFP virus in primary 283 cells based on the average peak titers and observed that infectivity exhibited the same 284 pattern as the ACE2 expression levels from the upper to lower respiratory tract ( Figure 285 6Bi-6Biv). Gene 1230 expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human 1231 airway epithelial cells and lung tissue abstract: Summary The mode of acquisition and causes for the variable clinical spectrum of COVID-19 remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore SARS-CoV-2 pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis. url: https://doi.org/10.1016/j.cell.2020.05.042 doi: 10.1016/j.cell.2020.05.042 id: cord-252232-vgq6gjpx author: Hou, Yuxuan title: Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry date: 2010-06-22 words: 3208.0 sentences: 159.0 pages: flesch: 57.0 cache: ./cache/cord-252232-vgq6gjpx.txt txt: ./txt/cord-252232-vgq6gjpx.txt summary: Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. However, although the genetically related SARS-like coronavirus (SL-CoV) has been identified in horseshoe bats of the genus Rhinolophus [5, 8, 12, 18] , its spike protein was not able to use the human ACE2 (hACE2) protein as a receptor [13] . To this end, we have extended our studies to include ACE2 molecules from different bat species and examined their interaction with the human SARS-CoV spike protein. Our results show that there is great genetic diversity among bat ACE2 molecules, especially at the key residues known to be important for interacting with the viral spike protein, and that ACE2s of Myotis daubentoni and Rhinolophus sinicus from Hubei province can support viral entry. abstract: The discovery of SARS-like coronavirus in bats suggests that bats could be the natural reservoir of SARS-CoV. However, previous studies indicated the angiotensin-converting enzyme 2 (ACE2) protein, a known SARS-CoV receptor, from a horseshoe bat was unable to act as a functional receptor for SARS-CoV. Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. The results show that ACE2s of Myotis daubentoni and Rhinolophus sinicus support viral entry mediated by the SARS-CoV S protein, albeit with different efficiency in comparison to that of the human ACE2. Further, the alteration of several key residues either decreased or enhanced bat ACE2 receptor efficiency, as predicted from a structural modeling study of the different bat ACE2 molecules. These data suggest that M. daubentoni and R. sinicus are likely to be susceptible to SARS-CoV and may be candidates as the natural host of the SARS-CoV progenitor viruses. Furthermore, our current study also demonstrates that the genetic diversity of ACE2 among bats is greater than that observed among known SARS-CoV susceptible mammals, highlighting the possibility that there are many more uncharacterized bat species that can act as a reservoir of SARS-CoV or its progenitor viruses. This calls for continuation and expansion of field surveillance studies among different bat populations to eventually identify the true natural reservoir of SARS-CoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-010-0729-6) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s00705-010-0729-6 doi: 10.1007/s00705-010-0729-6 id: cord-291916-5yqc3zcx author: Hozhabri, Hossein title: The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting date: 2020-08-05 words: 16737.0 sentences: 847.0 pages: flesch: 45.0 cache: ./cache/cord-291916-5yqc3zcx.txt txt: ./txt/cord-291916-5yqc3zcx.txt summary: abstract: Over the past two decades, there have been two major outbreaks where the crossover of animal Betacoronaviruses to humans has resulted in severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In December 2019, a global public health concern started with the emergence of a new strain of coronavirus (SARS-CoV-2 or 2019 novel coronavirus, 2019-nCoV) which has rapidly spread all over the world from its origin in Wuhan, China. SARS-CoV-2 belongs to the Betacoronavirus genus, which includes human SARS-CoV, MERS and two other human coronaviruses (HCoVs), HCoV-OC43 and HCoV-HKU1. The fatality rate of SARS-CoV-2 is lower than the two previous coronavirus epidemics, but it is faster spreading and the large number of infected people with severe viral pneumonia and respiratory illness, showed SARS-CoV-2 to be highly contagious. Based on the current published evidence, herein we summarize the origin, genetics, epidemiology, clinical manifestations, preventions, diagnosis and up to date treatments of SARS-CoV-2 infections in comparison with those caused by SARS-CoV and MERS-CoV. Moreover, the possible impact of weather conditions on the transmission of SARS-CoV-2 is also discussed. Therefore, the aim of the present review is to reconsider the two previous pandemics and provide a reference for future studies as well as therapeutic approaches. url: https://doi.org/10.3390/ijerph17165648 doi: 10.3390/ijerph17165648 id: cord-294069-7zr77r71 author: Hu, Xiaowen title: The distribution of SARS-CoV-2 contamination on the environmental surfaces during incubation period of COVID-19 patients date: 2020-09-30 words: 2527.0 sentences: 136.0 pages: flesch: 50.0 cache: ./cache/cord-294069-7zr77r71.txt txt: ./txt/cord-294069-7zr77r71.txt summary: In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. In addition, we synchronously sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the SARS-CoV-2 distribution on the environmental surfaces during the incubation period of COVID-19 patients. Then, medical staffs stayed in hotel immediately sampled their nasopharyngeal swabs and environmental surfaces, and transferred them to the hospital for further diagnosis Additionally, the frequency of washing behaviors of patients at the quarantine room, including face washing, hands washing, tooth brushing, bathing and excrement, were shown in Table 2 . Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient abstract: Roles of environmental factors in transmission of COVID-19 have been highlighted. In this study, we sampled the high-touch environmental surfaces in the quarantine room, aiming to detect the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the environmental surfaces during the incubation period of coronavirus disease 2019 (COVID-19) patients. Fifteen sites were sampled from the quarantine room, distributing in the functional areas such as bedroom, bathroom and living room. All environmental surface samples were collected with sterile polyester-tipped applicator pre-moistened in viral transport medium and tested for SARS-CoV-2. Overall, 34.1% of samples were detected positively for SARS-CoV-2. The positive rates of Patient A, B and C, were 46.2%, 0 and 61.5%, respectively. SARS-CoV-2 was detected positively in bedroom and bathroom, with the positive rate of 50.0% and 46.7%, respectively. In contrast, living room had no positive sample detected. Environmental contamination of SARS-CoV-2 distributes widely during the incubation period of CCOVID-19, and the positive rates of SARS-CoV-2 on environmental surfaces are relatively high in bathroom and bedroom. url: https://doi.org/10.1016/j.ecoenv.2020.111438 doi: 10.1016/j.ecoenv.2020.111438 id: cord-312652-zhccmfgw author: Hu, Xiumei title: Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA date: 2020-06-20 words: 3001.0 sentences: 176.0 pages: flesch: 50.0 cache: ./cache/cord-312652-zhccmfgw.txt txt: ./txt/cord-312652-zhccmfgw.txt summary: According to Chinese Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7), SARS-CoV-2 specific IgM becomes detectable around 3-5 days after onset and IgG reaches a titration of at least 4-fold increase during convalescence compared with the acute [9] . In order to establish a safe and accurate method for detecting SARS-CoV-2 specific antibodies, we retrospectively assessed the impact of sera heat-inactivation at 56℃ for 30 minutes on the levels of SARS-CoV-2 IgM or IgG antibodies. Therefore, our analysis provide evidence that sera inactivated by heating at 56℃ for 30 minutes could reduce the risk of virus contamination, and would not impair the detection efficacy of SARS-CoV-2 IgM or IgG testing using this ELISA assay. In summary, sera inactivated by heating at 56℃ for 30 minutes could minimize the risk of virus contamination and did not impair the positive detection rate using SARS-CoV-2 antibody detection kit (ELISA-immunoassay) and eventually represents a valuable contribution to a safer COVID-19 serological diagnosis. abstract: BACKGROUND: To establish a safe and accurate method for detecting SARS-CoV-2 IgM and IgG, we assessed the impact of sera after heat-inactivation on the SARS-CoV-2 IgM and IgG levels measured by ELISA-immunoassay. METHODS: The serum samples of 62 patients with COVID-19 and 18 healthy controls were collected in Hankou’s Hospital of Wuhan from February 27 to March 6, 2020. Before and after the samples were inactivated, the levels of IgM and IgG antibodies were measured. RESULTS: The indexes of antibodies after inactivated were significantly higher than those in fresh sera, while the positive rates in all participants or in patients with COVID-19 did not change. The positive coincidence rate, negative coincidence rate and total coincidence rate of IgM antibodies before and after inactivation were 100.00% (55/55), 96.00% (24/25) and 98.75% (79/80), respectively (κ=0.971, P<0.001), while those for IgG antibodies were 98.21% (55/56), 91.67% (22/24) and 98.75% (79/80) respectively (κ=0.910, P<0.001). These results showed a good consistency. CONCLUSIONS: Heating-activation does not decrease the diagnostic efficacy of SARS-CoV-2 IgM or IgG antibodies. Sera inactivated by heating at 56℃ for 30 minutes should be recommended to minimize the risk of virus contamination of laboratory staff. url: https://doi.org/10.1016/j.cca.2020.06.032 doi: 10.1016/j.cca.2020.06.032 id: cord-322908-e3gok0ot author: Huang, Fangfang title: A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) date: 2020-05-20 words: 5056.0 sentences: 275.0 pages: flesch: 42.0 cache: ./cache/cord-322908-e3gok0ot.txt txt: ./txt/cord-322908-e3gok0ot.txt summary: In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19. In this review, we summarized potential Chinese herbal medicines ( Table 2 ) that may treat COVID-19 by targeting proteins such as Spike protein, ACE2, 3CLpro, PLpro and RdRp. We also predicted the binding affinities between these compounds and COVID-19 related targets by molecular docking, with a focus on six compounds: quercetin, andrographolide, glycyrrhizic acid, baicalin, patchouli alcohol, and luteolin. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial abstract: The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global “pandemic”. At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19. url: https://www.sciencedirect.com/science/article/pii/S1043661820312378?v=s5 doi: 10.1016/j.phrs.2020.104929 id: cord-302608-fw4pmaoc author: Huang, Jiao-Mei title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date: 2020-03-19 words: 1890.0 sentences: 125.0 pages: flesch: 57.0 cache: ./cache/cord-302608-fw4pmaoc.txt txt: ./txt/cord-302608-fw4pmaoc.txt summary: However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human. The S-protein amino acid sequence identity between SARS-CoV-2 and related beta-CoVs showed that bat/Yunnan/RaTG13 shares highest similarity of 97.43%. abstract: The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability. url: https://doi.org/10.1101/2020.03.16.993816 doi: 10.1101/2020.03.16.993816 id: cord-309074-pys4aa60 author: Huang, Victoria W. title: Telehealth in the times of SARS-CoV-2 infection for the Otolaryngologist date: 2020-05-30 words: 2644.0 sentences: 154.0 pages: flesch: 48.0 cache: ./cache/cord-309074-pys4aa60.txt txt: ./txt/cord-309074-pys4aa60.txt summary: OBJECTIVE: In response to the American Academy of Otolaryngology – Head and Neck Surgery''s recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. In response to these evolving needs, the American Academy of Otolaryngology -Head and Neck Surgery (AAO-HNS) telemedicine committee has put forth new recommendations to prioritize novel applications of telehealth to help limit coronavirus disease pandemic spread while maintaining quality care 8 . As testing in the U.S. becomes more available in this era of SARS-CoV-2, telemedicine continues to take the main role of "forward triage", evaluating patients with respiratory symptoms before they arrive in hospitals 23 With the AAO-HNS recommending all otolaryngologists to limit patient care activities to time-sensitive, urgent, and emergent medical conditions, elective surgeries have been canceled with many outpatient clinics rescheduling appointments and transitioning to virtual visits 7, 8 . abstract: OBJECTIVE: In response to the American Academy of Otolaryngology – Head and Neck Surgery’s recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. With regulations for telemedicine loosened, new possibilities for the practice of otolaryngology have opened. To address the uncertain duration of this pandemic, a review was conducted of current literature on use of telemedicine services in the current SARS-CoV-2 pandemic and in previous national emergencies to reveal the role telemedicine can play for otolaryngology practices. DATA SOURCES: Pubmed articles with an independent search query were utilized. METHODS: Literature review performed by one author searched for all published English-language literature on telehealth in the SARS-CoV-2 era. Articles were considered for discussion if they provided relevant developments for telemedicine in the context of the SARS-CoV-2 pandemic. RESULTS: Telemedicine can be up-scaled in the current SARS-CoV-2 pandemic where exposure containment is of the utmost priority. With patient interaction possible through virtual communication, telemedicine allows continued patient care while minimizing the risk of viral spread. In the realm of otolaryngology, telemedicine has been used in the past during disasters with other studies demonstrating high diagnostic concordance with inpatient visits. Many institutions have recognized the potential for such care as they begin utilize both virtual visits and in-person care during this pandemic. CONCLUSION: To limit the spread of SARS-CoV-2, we support the AAO-HNS recommendation for the adoption of novel ways to employ telemedicine in this era. Many emergency departments and health care systems have the infrastructure necessary for synchronous video telemedicine visits that can be leveraged to provide quality care with patients. With the continued need to socially distance, telemedicine can protect both physicians and patients from unnecessary exposure to the virus. url: https://www.sciencedirect.com/science/article/pii/S2095881120300676?v=s5 doi: 10.1016/j.wjorl.2020.04.008 id: cord-329011-spiuqngp author: Huang, Yuan title: Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 date: 2020-08-03 words: 6045.0 sentences: 340.0 pages: flesch: 53.0 cache: ./cache/cord-329011-spiuqngp.txt txt: ./txt/cord-329011-spiuqngp.txt summary: The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. A large number of glycosylated S proteins cover the surface of SARS-CoV-2 and bind to the host cell receptor angiotensinconverting enzyme 2 (ACE2), mediating viral cell entry [8] . The SARS-CoV-2 S protein is highly conserved among all human coronaviruses (HCoVs) and is involved in receptor recognition, viral attachment, and entry into host cells. Structure of the S1 subunit The binding of virus particles to cell receptors on the surface of the host cell is the initiation of virus infection; therefore, receptor recognition is an important determinant of viral entry and a drug design target. Therefore, the development of antibodies targeting this functional motif may cross-bind and neutralize these two viruses and related CoVs. Antiviral peptides prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infection. abstract: Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein. url: https://doi.org/10.1038/s41401-020-0485-4 doi: 10.1038/s41401-020-0485-4 id: cord-315288-fcx4q6mp author: Hussain, Mohammed Hassan title: Tracheal swab from front of neck airway for SARS-CoV-2; a bronchial foreign body date: 2020-08-27 words: 1566.0 sentences: 105.0 pages: flesch: 62.0 cache: ./cache/cord-315288-fcx4q6mp.txt txt: ./txt/cord-315288-fcx4q6mp.txt summary: We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. Patients with front of neck airways, either in the form of a laryngectomy or tracheostomy stoma site, present a challenge in terms of testing for SARS-CoV-2. There is a need for clear guidance on how to test patients with front of neck airways for SARS-CoV-2. abstract: We report the case of a bronchial foreign body, following a tracheostomy site swab for SARS-CoV-2, aiming to raise awareness and vigilance. A qualified nurse was performing a routine SARS-CoV-2 swab on a 51-year-old woman, fitted with a tracheostomy in the recent past following a craniotomy. This was part of the discharging protocol to a nursing home. During the sampling, part of the swab stylet snapped and was inadvertently dropped through the tracheostomy site. Initial CT imaging was reported as showing no signs of a foreign body but some inflammatory changes. Bedside flexible endoscopy through the tracheostomy site revealed the swab in a right lobar bronchus. This was subsequently removed by flexible bronchoscopy. This case highlights the need for clear guidance on how samples for SARS-CoV-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. url: https://doi.org/10.1136/bcr-2020-237787 doi: 10.1136/bcr-2020-237787 id: cord-349117-xfir3m5p author: Hyseni, Inesa title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 words: 8298.0 sentences: 403.0 pages: flesch: 52.0 cache: ./cache/cord-349117-xfir3m5p.txt txt: ./txt/cord-349117-xfir3m5p.txt summary: After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody. abstract: The recent outbreak of a novel Coronavirus (SARS-CoV-2) and its rapid spread across the continents has generated an urgent need for assays to detect the neutralising activity of human sera or human monoclonal antibodies against SARS-CoV-2 spike protein and to evaluate the serological immunity in humans. Since the accessibility of live virus microneutralisation (MN) assays with SARS-CoV-2 is limited and requires enhanced bio-containment, the approach based on “pseudotyping” can be considered a useful complement to other serological assays. After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. The results obtained with pseudotype-based neutralisation assays mirrored those obtained when the same panel of sera was tested against the wild type virus, showing an evident convergence of the pseudotype-based neutralisation and MN results. The overall results lead to the conclusion that the pseudotype-based neutralisation assay is a valid alternative to using the wild-type strain, and although this system needs to be optimised and standardised, it can not only complement the classical serological methods, but also allows serological assessments to be made when other methods cannot be employed, especially in a human pandemic context. url: https://www.ncbi.nlm.nih.gov/pubmed/32927639/ doi: 10.3390/v12091011 id: cord-328289-3h3kmjlz author: Iadecola, Costantino title: Effects of COVID-19 on the nervous system date: 2020-08-19 words: 6524.0 sentences: 349.0 pages: flesch: 40.0 cache: ./cache/cord-328289-3h3kmjlz.txt txt: ./txt/cord-328289-3h3kmjlz.txt summary: Another Parkinson''s disease patient with obesity, hypertension and diabetes, exhibited at autopsy, in addition to hypoxic-ischemic neuronal damage, microhemorrhages, white matter lesions and enlarged perivascular spaces, but no evidence of SARS-CoV-2 in the brain (Kantonen et al., 2020) . The encephalopathy is most likely a consequence of systemic factors, such as cytokine sickness, hypoxia and metabolic dysfunction due to peripheral organ failure, while the strokes seem to be related more to hypercoagulability and endothelial injury than to SARS-CoV-2 vasculitis affecting brain vessels. In some cases, the possibility of a SARS-CoV-2 encephalitis could not be ruled out based on the potential for the virus to infect neurons (Song et al., 2020) , but definitive clinical and pathological evidence of neurotropism is lacking. abstract: Summary Neurological complications have emerged as a significant cause of morbidity and mortality in the ongoing COVID-19 pandemic. Beside respiratory insufficiency, many hospitalized patients exhibit neurological manifestations, ranging from headache and loss of smell, to confusion and disabling strokes. COVID-19 is also anticipated to take a toll on the nervous system in the long term. Here we will provide a critical appraisal of the potential for neurotropism and mechanisms of neuropathogenesis of SARS-CoV-2, as they relate to the acute and chronic neurological consequences of the infection. Finally, we will examine potential avenues for future research and therapeutic development. url: https://api.elsevier.com/content/article/pii/S0092867420310709 doi: 10.1016/j.cell.2020.08.028 id: cord-263945-yli5suxb author: Iancu, Gabriela Mariana title: Viral exanthema as manifestation of SARS-CoV-2 infection: A case report date: 2020-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity. url: https://www.ncbi.nlm.nih.gov/pubmed/32871902/ doi: 10.1097/md.0000000000021810 id: cord-331094-22366b81 author: Ianevski, Aleksandr title: Potential Antiviral Options against SARS-CoV-2 Infection date: 2020-06-13 words: 6822.0 sentences: 424.0 pages: flesch: 49.0 cache: ./cache/cord-331094-22366b81.txt txt: ./txt/cord-331094-22366b81.txt summary: We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs. abstract: As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32545799/ doi: 10.3390/v12060642 id: cord-312160-2820aftb author: Ibrahim, Mahmoud A.A. title: In silico Drug Discovery of Major Metabolites from Spices as SARS-CoV-2 Main Protease Inhibitors date: 2020-10-08 words: 2443.0 sentences: 162.0 pages: flesch: 51.0 cache: ./cache/cord-312160-2820aftb.txt txt: ./txt/cord-312160-2820aftb.txt summary: Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). The binding energies of the investigated spices compounds with SARS-CoV-2 M pro were estimated using molecular mechanical-generalized Born surface area (MM-GBSA) approach with modified GB model (igb=2) implemented in AMBER16 software [27] . The physicochemical parameters of the most promising natural spices as SARS-CoV-2 M pro inhibitors were predicted using the online Molinspiration cheminformatics software %ABS was estimated as follows [28] : The online web-based tools of SwissTargetPredicition (http://www.swisstargetprediction.ch) were applied to predict the biological targets for the most promising natural spices as SARS-CoV-2 M pro inhibitors. Since the main protease of SARS-CoV-2 (M pro ) plays a critical role in the viral replication process, structure-based computational modeling of ligand-receptor interactions and molecular dynamics has been used to screen metabolites from common spices as potential M pro inhibitors. abstract: Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (M(pro)), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as M(pro) inhibitors with binding energies of −9.7 and −9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to M(pro)'s active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of −44.8, −34.2 and −34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing. url: https://www.sciencedirect.com/science/article/pii/S0010482520303772?v=s5 doi: 10.1016/j.compbiomed.2020.104046 id: cord-306177-5wefp31y author: Iheagwam, Franklyn Nonso title: Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants date: 2020-09-12 words: 4804.0 sentences: 251.0 pages: flesch: 42.0 cache: ./cache/cord-306177-5wefp31y.txt txt: ./txt/cord-306177-5wefp31y.txt summary: e Unites States Food and Drug Administration-(USFDA-) approved drugs [26] , drugbank [27, 28] , traditional Ayurvedic, Chinese and natural medicine [20, [28] [29] [30] [31] , dark chemical matter, and fooDB [25] are some of the ZINC database subsets that have been rigourously screened for molecules to combat SARS-CoV-2 with main protease, RNA-dependent RNA polymerase, and angiotensin-converting enzyme-2 as the major therapeutic targets. Hence, this study analysed a plethora of natural products (NPs) from African medicinal plants with known bioactivities in human as therapeutic candidates targeting and inhibiting SARS-CoV-2 RNA synthesis, replication, structural protein function, and host-specific receptors/enzymes. In the course of drug discovery, structure-based virtual screening is a computational approach utilised to identify promising novel small chemical ligands from curated chemical compound databases with potential activity against drug targets [48] . abstract: The COVID-19 pandemic, which started in Wuhan, China, has spread rapidly over the world with no known antiviral therapy or vaccine. Interestingly, traditional Chinese medicine helped in flattening the pandemic curve in China. In this study, molecules from African medicinal plants were analysed as potential candidates against multiple SARS-CoV-2 therapeutic targets. Sixty-five molecules from the ZINC database subset (AfroDb Natural Products) were virtually screened with some reported repurposed therapeutics against six SARS-CoV-2 and two human targets. Molecular docking, druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the best hits were further simulated. Of the 65 compounds, only three, namely, 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside found in almond (Terminalia catappa), grape (Vitis vinifera), and common verbena (Verbena officinalis), were able to bind to all eight targets better than the reported repurposed drugs. The findings suggest these molecules may play a role as therapeutic leads in tackling this pandemic due to their multitarget activity. url: https://doi.org/10.1155/2020/1878410 doi: 10.1155/2020/1878410 id: cord-284498-54j6ys8s author: Ihsanullah, Ihsanullah title: Coronavirus 2 (SARS-CoV-2) in water environments: Current status, challenges and research opportunities date: 2020-10-16 words: 5702.0 sentences: 398.0 pages: flesch: 47.0 cache: ./cache/cord-284498-54j6ys8s.txt txt: ./txt/cord-284498-54j6ys8s.txt summary: Some of the significant challenges and research opportunities are the development of standard techniques for the detection and quantification of SARS-CoV-2 in the water phase, assessment of favorable environments for its survival and decay in water; and development of effective strategies for elimination of the novel virus from water. Development of effective standard techniques for the detection and quantification of SARS-CoV-2 in water, assessment of the existing water purification technologies and development of novel advanced water treatment systems are major challenges and open research opportunities. Furthermore, careful surveillance of water and wastewater to be used as an early warning tool for such outbreaks in future, understanding the survival and decay mechanism of the novel virus in water and wastewater, analysis of potential pathways of SARS-CoV-2 into water bodies are other potential research opportunities for environmental researchers [40] [41] [42] [43] [44] . abstract: The outbreak of COVID-19 has posed enormous health, social, environmental and economic challenges to the entire human population. Nevertheless, it provides an opportunity for extensive research in various fields to evaluate the fate of the crisis and combat it. The apparent need for imperative research in the biological and medical field is the focus of researchers and scientists worldwide. However, there are some new challenges and research opportunities in the field of water and wastewater treatment concerning the novel coronavirus 2 (SARS-CoV-2). This article briefly summarizes the latest literature reporting the presence of SARS-CoV-2 in water and wastewater/sewage. Furthermore, it highlights the challenges, potential opportunities and research directions in the water and wastewater treatment field. Some of the significant challenges and research opportunities are the development of standard techniques for the detection and quantification of SARS-CoV-2 in the water phase, assessment of favorable environments for its survival and decay in water; and development of effective strategies for elimination of the novel virus from water. Advancement in research in this domain will help to protect the environment, human health, and managing this type of pandemic in the future. url: https://api.elsevier.com/content/article/pii/S2214714420306127 doi: 10.1016/j.jwpe.2020.101735 id: cord-293056-kz3w0nfh author: Indes, Jeffrey E. title: Early Experience with Arterial Thromboembolic Complications in Patents with COVID-19 date: 2020-08-28 words: 1933.0 sentences: 125.0 pages: flesch: 51.0 cache: ./cache/cord-293056-kz3w0nfh.txt txt: ./txt/cord-293056-kz3w0nfh.txt summary: A retrospective case-control study design was used to identify, characterize and evaluate potential risk factors for arterial thromboembolic disease in SARS-CoV-2 positive patients. Although not statistically significant, in patients with arterial thromboembolism, patients who were SARS-CoV-2 positive compared to those testing negative or not tested tended to be male (66.7 % v. Treatment of arterial thromboembolic disease in the COVID-19 positive patients included open thromboembolectomy in 6 patients (40%), anticoagulation alone in 4 (26.7%) and 5 (33.3%) did not require or their overall illness severity precluded additional treatment. The SARS-CoV-2 positive group included patients with a range of COVID-19 16 symptomatology (mild to severe) as well as those tested as part of routine preoperative 17 preparation. Patients with arterial thrombosis who were SARS-CoV-10 2 positive had significantly higher D-dimer levels, BMI, were younger, and less often on 11 antiplatelet medications as compared to patients who were SARS-CoV-2 negative or not tested. abstract: INTRODUCTION: Little is known about the arterial complications and hypercoagulability associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We sought to characterize our experience with arterial thromboembolic complications in patients with hospitalized for coronavirus disease 2019 (COVID-19). METHODS: All patients admitted from March 1 to April 20, 2020 and who underwent carotid, upper, lower and aortoiliac arterial duplex, CT angiogram or MRA for suspected arterial thrombosis were included. A retrospective case-control study design was used to identify, characterize and evaluate potential risk factors for arterial thromboembolic disease in SARS-CoV-2 positive patients. Demographics, characteristics and laboratory values were abstracted and analyzed. RESULTS: During the study period, 424 patients underwent 499 arterial duplex, CT angiogram or MRA imaging studies with overall 9.4% positive for arterial thromboembolism. Of the 40 patients with arterial thromboembolism, 25 (62.5%) were SARS-CoV-2 negative or admitted for unrelated reasons and 15 (37.5%) were SARS-CoV-2 positive. The odds ratio for arterial thrombosis in COVID-19 was 3.37 (95% CI 1.68 – 6.78, p=0.001). Although not statistically significant, in patients with arterial thromboembolism, patients who were SARS-CoV-2 positive compared to those testing negative or not tested tended to be male (66.7 % v. 40.0%, p=0.191), have a less frequent history of former or active smoking (42.9% vs 68.0%, p=0.233) and have a higher white blood cell count (WBC 14.5 vs. 9.9, p=0.208). While the SARS-CoV-2 positive patients trended toward a higher the neutrophil-to-lymphocyte ratio (8.9 vs. 4.1, p=0.134), CPK level (359.0 vs. 144.5, p=0.667), CRP level (24.2 vs. 13.8, p=0.627), LDH level (576.5 vs. 338.0, p=0.313) and ferritin level (974.0 vs. 412.0, p=0.47), these did not reach statistical significance. Patients with arterial thromboembolic complications and SARS-CoV-2 positive when compared to SARS-CoV-2 negative or admitted for unrelated reasons were younger (64 vs. 70 years, p=0.027), had a significantly higher body mass index (BMI) (32.6 vs. 25.5, p=0.012), a higher D-dimer at the time of imaging (17.3 vs. 1.8, p=0.038), a higher average in hospital D-dimer (8.5 vs. 2.0, p=0.038), a greater distribution of patients with clot in the aortoiliac location (5 vs. 1, p=0.040), less prior use of any antiplatelet medication (21.4% vs. 62.5%, p=0.035) and a higher mortality rate (40.0 % vs. 8.0%, p=0.041). Treatment of arterial thromboembolic disease in the COVID-19 positive patients included open thromboembolectomy in 6 patients (40%), anticoagulation alone in 4 (26.7%) and 5 (33.3%) did not require or their overall illness severity precluded additional treatment. CONCLUSIONS: Patients with SAR-CoV-2 are at risk for acute arterial thromboembolic complications despite a lack of conventional risk factors. A hyperinflammatory state may be responsible for this phenomenon with a preponderance for aortoiliac involvement. These findings provide an early characterization of arterial thromboembolic disease in SARS-CoV-2 patients. url: https://www.sciencedirect.com/science/article/pii/S0741521420318796?v=s5 doi: 10.1016/j.jvs.2020.07.089 id: cord-307860-iqk1yiw4 author: Ionescu, Mihaela Ileana title: An Overview of the Crystallized Structures of the SARS-CoV-2 date: 2020-10-24 words: 9856.0 sentences: 668.0 pages: flesch: 57.0 cache: ./cache/cord-307860-iqk1yiw4.txt txt: ./txt/cord-307860-iqk1yiw4.txt summary: Structures retrieved from PDB (August 12, 2020) were analyzed for relevant information on COVID-19 infection, synthesis of new inhibitors, SARS-CoV-2 interaction with host receptors, and the neutralizing antibodies interactions with spike glycoprotein. The first X-ray structure found (PDB ID 6LU7) belongs to the nonstructural protein 5 (3C-like protease) of the SARS-CoV-2 in complex with the Michael acceptor-based inhibitor N3 (PRD_002214). There is a cryo-EM crystal structure of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex (nsp12/nsp8/nsp7) with the antiviral drug remdesivir (PDB ID 7BV2) [37] . Previous studies on the crystal structures of SARS-CoV S glycoprotein mutants neutralized by 80R-specific antibodies have been considered a hope for the immunotherapeutic Fig. 8 The phylogenetic tree (cladogram) of the CoVs Spike (S) sequences of CoVs with different origin. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites abstract: Many research teams all over the world focus their research on the SARS-CoV-2, the new coronavirus that causes the so-called COVID-19 disease. Most of the studies identify the main protease or 3C-like protease (M(pro)/3CL(pro)) as a valid target for large-spectrum inhibitors. Also, the interaction of the human receptor angiotensin-converting enzyme 2 (ACE2) with the viral surface glycoprotein (S) is studied in depth. Structural studies tried to identify the residues responsible for enhancement/weaken virus-ACE2 interactions or the cross-reactivity of the neutralizing antibodies. Although the understanding of the immune system and the hyper-inflammatory process in COVID-19 are crucial for managing the immediate and the long-term consequences of the disease, not many X-ray/NMR/cryo-EM crystals are available. In addition to 3CL(pro), the crystal structures of other nonstructural proteins offer valuable information for elucidating some aspects of the SARS-CoV-2 infection. Thus, the structural analysis of the SARS-CoV-2 is currently mainly focused on three directions—finding M(pro)/3CL(pro) inhibitors, the virus-host cell invasion, and the virus-neutralizing antibody interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10930-020-09933-w) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/33098476/ doi: 10.1007/s10930-020-09933-w id: cord-328361-hyrke6j2 author: Ithete, Ndapewa Laudika title: Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa date: 2013-10-17 words: 1186.0 sentences: 60.0 pages: flesch: 54.0 cache: ./cache/cord-328361-hyrke6j2.txt txt: ./txt/cord-328361-hyrke6j2.txt summary: A novel clade 2c betacoronavirus, termed Middle East respiratory syndrome (MERS)-CoV, was recently identified as the causative agent of a severe respiratory disease that is mainly affecting humans on the Arabian Peninsula (1) . Extending on previous work (2), we described European Pipistrellus bat-derived CoVs that are closely related to MERS-CoV (3) . Screening for CoVs was done by nested reverse transcription PCR using broadly reactive oligonucleotide primers targeting a conserved region in the RNA-dependent RNA polymerase (RdRp) gene (online Technical Appendix). PCR amplicons for 4 positive specimens yielded alphacoronavirus sequences related to recently described bat alphacoronaviruses from South Africa (4) . A Bayesian phylogenetic analysis of the 816-nt RdRp sequence confirmed the close relationship between PML/2011 and MERS-CoV (Figure) . Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/24050621/ doi: 10.3201/eid1910.130946 id: cord-342538-5bwsm290 author: Izquierdo Lara, R. W. title: Monitoring SARS-CoV-2 circulation and diversity through community wastewater sequencing date: 2020-09-22 words: 5031.0 sentences: 281.0 pages: flesch: 56.0 cache: ./cache/cord-342538-5bwsm290.txt txt: ./txt/cord-342538-5bwsm290.txt summary: Here we have explored the possibility of using next-generation sequencing (NGS) of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level from routine wastewater testing, and compared these results with the virus diversity in patients from the Netherlands and Belgium. Low frequency variant (LFV) analysis showed that some known LFVs can be associated with particular clusters within a clade, different to those of their consensus sequences, suggesting the presence of at least 2 clades within a single sewage sample. Moreover, we detected a total of 51 novel mutations present in sewage consensus sequences that were not previously reported (supplementary Table S2 ), of which 48 were supported by coverage above the set thresholds to be considered as high quality (coverage >30x for Nanopore; and coverage >5X and Phred score >30 for Illumina). abstract: The current SARS-CoV-2 pandemic has rapidly become a major global health problem for which public health surveillance is crucial to monitor virus spread. Given the presence of viral RNA in feces in around 40% of infected persons, wastewater-based epidemiology has been proposed as an addition to disease-based surveillance to assess the spread of the virus at the community level. Here we have explored the possibility of using next-generation sequencing (NGS) of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level from routine wastewater testing, and compared these results with the virus diversity in patients from the Netherlands and Belgium. Phylogenetic analysis revealed the presence of viruses belonging to the most prevalent clades (19A, 20A and 20B) in both countries. Clades 19B and 20C were not identified, while they were present in clinical samples during the same period. Low frequency variant (LFV) analysis showed that some known LFVs can be associated with particular clusters within a clade, different to those of their consensus sequences, suggesting the presence of at least 2 clades within a single sewage sample. Additionally, combining genome consensus and LFV analyses we found a total of 57 unique mutations in the SARS-CoV-2 genome which have not been described before. In conclusion, this work illustrates how NGS analysis of wastewater can be used to approximate the diversity of SARS-CoV-2 viruses circulating in a community. url: https://doi.org/10.1101/2020.09.21.20198838 doi: 10.1101/2020.09.21.20198838 id: cord-312486-rumqopg0 author: Jacob, Chaim Oscar title: On the genetics and immunopathogenesis of COVID-19 date: 2020-09-10 words: 11514.0 sentences: 579.0 pages: flesch: 44.0 cache: ./cache/cord-312486-rumqopg0.txt txt: ./txt/cord-312486-rumqopg0.txt summary: The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] . abstract: Most severe cases with COVID-19, especially those with pulmonary failure, are not a consequence of viral burden and/or failure of the ‘adaptive’ immune response to subdue the pathogen by utilizing an adequate ‘adaptive’ immune defense. Rather it is a consequence of immunopathology, resulting from imbalanced innate immune response, which may not be linked to pathogen burden at all. In fact, it might be described as an autoinflammatory disease. The Kawasaki-like disease seen in children with SARS-CoV-2 exposure might be another example of similar mechanism. url: https://api.elsevier.com/content/article/pii/S1521661620307518 doi: 10.1016/j.clim.2020.108591 id: cord-337105-jlmh79qv author: Jacob, Fadi title: Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium date: 2020-09-21 words: 9954.0 sentences: 567.0 pages: flesch: 53.0 cache: ./cache/cord-337105-jlmh79qv.txt txt: ./txt/cord-337105-jlmh79qv.txt summary: We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. QPCR analysis also showed higher levels of ACE2 and TMPRSS2 expression in CPOs at 50 DIV and 100 DIV than in hippocampal organoids ( Figure S2D ) Together, these results show that our CPOs exhibit a similar transcriptome as adult human choroid plexus tissue and express markers for choroid plexus epithelial cells and SARS-CoV-2 receptors, representing a suitable experimental model to study SARS-CoV-2 infection. Our finding that dysregulated gene expression varies widely among hepatocyte, intestinal, and choroid plexus organoids infected with SARS-CoV-2 suggests unique responses in different cell types and highlights the need for diverse human cellular model systems when studying the disease. abstract: Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function are not well understood. Here we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies. url: https://www.sciencedirect.com/science/article/pii/S193459092030463X?v=s5 doi: 10.1016/j.stem.2020.09.016 id: cord-305931-0pgu2gvh author: Janus, Scott E title: COVID19: a case report of thrombus in transit date: 2020-06-17 words: 1431.0 sentences: 85.0 pages: flesch: 43.0 cache: ./cache/cord-305931-0pgu2gvh.txt txt: ./txt/cord-305931-0pgu2gvh.txt summary: In view of the fact that the utility of tissue plasminogen activator in this population is not well studied, we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. 4 Although the utility of tissue plasminogen activator (TPA) for thrombus in transit in other clinical settings has previously been reported, 5 the literature regarding cardiovascular events in SARS-CoV-2 remains scarce; we therefore describe the case of a 64-year-old male who presented with Learning points SARS-CoV-2 pneumonia, who was found to have extensive clot in transit on echocardiography and underwent successful lytic therapy. In view of the fact that the utility of TPA in this population is not well studied, 10 we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. abstract: BACKGROUND: The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality, not only through devastating lung injury, but also due to multiple malfunctions in the cardiovascular system. The primary aetiology is believed to be mediated through lung alveolar injury; however, a few published reports have linked SARS-CoV-2 to significant organ dysfunction, venous thrombo-embolism, and coagulopathy. In view of the fact that the utility of tissue plasminogen activator in this population is not well studied, we present this case of rapid improvement in oxygenation after successful lytic therapy for thrombus in transit in this patient with SARS-CoV-2. CASE SUMMARY: We discuss a patient admitted with SARS-CoV-2 pneumonia. Due to the development of dramatic hypoxia, he underwent echocardiography which demonstrated extensive thrombus in transit. He received successful thrombolytic therapy with tissue plasminogen activator, with subsequent improvement in oxygenation. The patient was successfully discharged home on 2 L of oxygen via nasal cannula, and continues to improve at follow-up with his cardiologist and primary care physician. CONCLUSION: This case not only highlights embolic causes of hypoxia in SARS-CoV-2, but demonstrates the important utility of an echocardiogram and tissue plasminogen activator in this population. url: https://www.ncbi.nlm.nih.gov/pubmed/33089047/ doi: 10.1093/ehjcr/ytaa189 id: cord-300399-21xozruq author: Jayamohan, Harikrishnan title: SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations date: 2020-10-18 words: 13003.0 sentences: 770.0 pages: flesch: 44.0 cache: ./cache/cord-300399-21xozruq.txt txt: ./txt/cord-300399-21xozruq.txt summary: This review paper examines current molecular diagnostic tools (Fig. 1) , such as amplification-based (including CRISPR-Cas based), antibody and antigen tests, and sequencing, utilized for the detection of SARS-CoV-2. In addition, we also discuss sample preparation aspects that are relevant to wider utilization and point-of-care (POC) deployment of COVID-19 diagnostic tests (PCR, isothermal amplification, and sequencing-including library preparation). RT-PCR broadly involves four steps-lysis of SARS-CoV-2 in the sample, purification of the viral RNA, reverse transcription to complementary DNA (cDNA), and amplification of specific regions of the cDNA, and finally, optical detection of the amplified cDNA. The assay can detect the virus from respiratory swab samples with sensitivity comparable to that of the US Centers for Disease Control and Prevention (CDC) SARS-CoV-2 real-time RT-PCR assay in 30-40 min. Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples abstract: The unprecedented global pandemic known as SARS-CoV-2 has exercised to its limits nearly all aspects of modern viral diagnostics. In doing so, it has illuminated both the advantages and limitations of current technologies. Tremendous effort has been put forth to expand our capacity to diagnose this deadly virus. In this work, we put forth key observations in the functionality of current methods for SARS-CoV-2 diagnostic testing. These methods include nucleic acid amplification–, CRISPR-, sequencing-, antigen-, and antibody-based detection methods. Additionally, we include analysis of equally critical aspects of COVID-19 diagnostics, including sample collection and preparation, testing models, and commercial response. We emphasize the integrated nature of assays, wherein issues in sample collection and preparation could impact the overall performance in a clinical setting. url: https://www.ncbi.nlm.nih.gov/pubmed/33073312/ doi: 10.1007/s00216-020-02958-1 id: cord-353777-t8q99tlq author: Jia, Yong title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 words: 3217.0 sentences: 180.0 pages: flesch: 58.0 cache: ./cache/cord-353777-t8q99tlq.txt txt: ./txt/cord-353777-t8q99tlq.txt summary: The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. The discrepant phylogenies for the spike protein and its 23 receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARSDespite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that 25 leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27 th January 2020 from 26 abstract: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. url: https://doi.org/10.1101/2020.04.09.034942 doi: 10.1101/2020.04.09.034942 id: cord-267458-uofy7jyx author: Jiang, Xiao-Lin title: Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China date: 2020-04-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Data concerning the transmission of SARS-CoV-2 in asymptomatic and paucisymptomatic patients are lacking. We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight (53%) of 15 members from three families were confirmed with SARS-CoV-2 infection. Of eight patients, three were asymptomatic and one was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household. The complete genomes of SARS-CoV-2 from the patients were >99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries. url: https://doi.org/10.1093/infdis/jiaa206 doi: 10.1093/infdis/jiaa206 id: cord-325234-skshcrh1 author: Jin, Tingxu title: SARS-CoV-2 presented in the air of an intensive care unit (ICU) date: 2020-08-15 words: 4276.0 sentences: 205.0 pages: flesch: 54.0 cache: ./cache/cord-325234-skshcrh1.txt txt: ./txt/cord-325234-skshcrh1.txt summary: Therefore, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, it is necessary to 1) determine whether SARS-CoV-2 particles are present in the indoor air and 2) determine whether recovered patients are still shedding virus, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. To date, some studies have reported the presence of SARS-CoV-2 particles in the air in isolation rooms from hospitals treating COVID-19 patients (Yuanfang J,2020; Guo, Wang, Zhang, Li, & Chen,2020; Joshua L. Therefore, our study aims to 1) determine whether SARS-CoV-2 particles are present in the indoor air, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, and 2) determine whether recovered patients are still shedding SARS-CoV-2 particles, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. Our findings revealed the presence of SARS-CoV-2 in the indoor air of the ICU and indicate that the virus may be shed via aerosol for days, even after a patient has tested negative. abstract: As coronavirus disease 2019 (COVID-19) is spreading worldwide, there have been arguments regarding the aerosol transmission of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, some re-detectable positive (RP) patients have been reported. However, little attention has been given to the follow-up of recovered patients, and there is no environmental evidence to determine whether these patients continue to shed the virus after they test negative. Therefore, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, it is necessary to 1) determine whether SARS-CoV-2 particles are present in the indoor air and 2) determine whether recovered patients are still shedding virus, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. In this study, surface and air samples were collected from an intensive care unit (ICU) containing one ready-for-discharge patient. All surface samples tested negative, but the air samples tested positive for SARS-CoV-2. This implies that SARS-CoV-2 particles may be shed in aerosol form for days after patients test negative. This finding may be one of the reasons for the observation of RP patients; therefore, there is a need for improved clinical and disease management guidelines for recovered COVID-19 patients. url: https://www.sciencedirect.com/science/article/pii/S2210670720306661?v=s5 doi: 10.1016/j.scs.2020.102446 id: cord-274506-fzcuu4ma author: Jo, Seri title: Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors date: 2019-09-12 words: 4210.0 sentences: 247.0 pages: flesch: 51.0 cache: ./cache/cord-274506-fzcuu4ma.txt txt: ./txt/cord-274506-fzcuu4ma.txt summary: While PLpro cuts the first three cleavage sites of its polyprotein, 3CLpro is responsible for cleavage of the remaining eleven locations resulting in release of a total of 16 non-structural proteins (nsp) in both SARS-and MERS-CoVs. The homodimeric form of 3CLpro is active in the presence of substrates. In this study, we used a proteolytic method to probe MERS-CoV 3CLpro inhibitory compounds with a synthetic peptide labelled with the EDANS-DABCYL FRET (Fluorescence resonance energy transfer) pair (Liu et al., 2005) . The proteolytic assay using MERS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The four compounds showed the severely reduced fluorescent intensity and thus represented their MERS-CoV 3CLpro inhibitory activity. In this study, we assayed the inhibitory activity of various flavonoids against MERS-CoV 3CLpro. The analysis of the four compounds with their homologs using an induced-fit docking study provided an insight of flavonoid scaffolds required to bind with MERS-CoV 3CLpro. abstract: Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a zoonotic virus transmitted between animals and human beings. It causes MERS with high mortality rate. However, no vaccine or specific treatment is currently available. Since antiviral activity of some flavonoids is known, we applied a flavonoid library to probe inhibitory compounds against MERS‐CoV 3C‐like protease (3CLpro). Herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside and helichrysetin were found to block the enzymatic activity of MERS‐CoV 3CLpro. The binding of the four flavonoids was also confirmed independently using a tryptophan‐based fluorescence method. The systematic comparison of the binding affinity of flavonoids made it possible to infer their scaffolds and functional groups required to bind with MERS‐CoV 3CLpro. An induced‐fit docking analysis revealed that S1 and S2 sites play a role in interaction with flavonoids. The experimental and computational study showed that flavonol and chalcone are favourite scaffolds to bind with the catalytic site of MERS‐CoV 3CLpro. It was also deduced that some flavonoid derivatives with hydrophobic or carbohydrate attached to their core structures have a good inhibitory effect. Therefore, we suggest that flavonoids with these characteristics can be used as templates to develop potent MERS‐CoV 3CLpro inhibitors. url: https://doi.org/10.1111/cbdd.13604 doi: 10.1111/cbdd.13604 id: cord-334976-53cd16w5 author: Jo, Seri title: Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro date: 2020-08-04 words: 3659.0 sentences: 222.0 pages: flesch: 55.0 cache: ./cache/cord-334976-53cd16w5.txt txt: ./txt/cord-334976-53cd16w5.txt summary: An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. The proteolytic assay using SARS-CoV-2 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The compound showed the severely reduced fluorescent intensity and thus represented their SARS-CoV-2 3CLpro inhibitory activity. Among them, baicalin, herbacetin and pectolinarin revealed the prominent inhibitory activity against SARS-CoV-2 3CLpro. The binding modes of herbacetin and pectolinarin were similar to those obtained from the docking study of the catalytic domain of SARS-CoV 3CLpro 21 . In the previous results of SARS-CoV 3CLpro 21 , only the three effect flavonoids (herbacetin, pectolinarin, and rhoifolin) were mentioned. abstract: Coronavirus disease 2019 (COVID-19) has been a pandemic disease of which the termination is not yet predictable. Currently, researches to develop vaccines and treatments is going on globally to cope with this disastrous disease. Main protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the good targets to find antiviral agents before vaccines are available. Some flavonoids are known to inhibit 3CLpro from SARS-CoV which causes SARS. Since their sequence identity is 96%, a similar approach was performed with a flavonoid library. Baicalin, herbacetin, and pectolinarin have been discovered to block the proteolytic activity of SARS-CoV-2 3CLpro. An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. However, their binding affinities are different due to the usage of whole SARS-CoV-2 3CLpro in this study. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. This study suggests important scaffolds to design 3CLpro inhibitors to develop antiviral agents or health-foods and dietary supplements to cope with SARS-CoV-2. url: https://doi.org/10.1080/14756366.2020.1801672 doi: 10.1080/14756366.2020.1801672 id: cord-348899-vynk8q8c author: Jo, Seri title: Inhibition of SARS-CoV 3CL protease by flavonoids date: 2019-11-14 words: 3989.0 sentences: 236.0 pages: flesch: 54.0 cache: ./cache/cord-348899-vynk8q8c.txt txt: ./txt/cord-348899-vynk8q8c.txt summary: A synthetic peptide labelled with an Edans-Dabcyl FRET (Fluorescence resonance energy transfer) pair 12 was used to search SARS-CoV 3CLpro inhibitory compounds against a flavonoid library. The proteolytic assay using the SARS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate the artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The three compounds showed the severely reduced fluorescent intensity and thus represented their SARS-CoV 3CLpro inhibitory activity. The interactions between SARS-CoV 3CLpro and three inhibitory flavonoids were analysed to predict their binding affinities. We have created a library of flavonoids to systematically investigate SARS-CoV 3CLpro inhibitory compound by a FRET method. Herbacetin, rhoifolin and pectolinarin were the best inhibitory compounds against SARS-CoV 3CLpro in the flavonoid library. In order to predict the flavonoid scaffolds needed to interact with the catalytic site of SARS-CoV 3CLpro, an induced-fit docking study was performed and analysed. abstract: There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors. url: https://doi.org/10.1080/14756366.2019.1690480 doi: 10.1080/14756366.2019.1690480 id: cord-338923-hc7gagnq author: Jääskeläinen, AJ title: Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation date: 2020-06-15 words: 2101.0 sentences: 131.0 pages: flesch: 53.0 cache: ./cache/cord-338923-hc7gagnq.txt txt: ./txt/cord-338923-hc7gagnq.txt summary: We compared the performance of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-CoV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). In this study, we assessed the specificity and sensitivity of six commercial immunoassays for the detection of SARS-CoV-2 antibodies, including two rapid lateral flow tests, in comparison with a neutralisation test. abstract: There is an urgent need for reliable high-throughput serological assays for the management of the ongoing COVID-19 pandemic. Preferably, the performance of serological tests for a novel virus should be determined with clinical specimens against a gold standard, i.e. virus neutralisation. We compared the performance of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-CoV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Two specimen panels from serum samples sent to Helsinki University Hospital Laboratory (HUSLAB) were compiled: the patient panel (N=70) included sera from PCR confirmed COVID-19 patients, and the negative panel (N=81) included sera sent for screening of autoimmune diseases and respiratory virus antibodies in 2018 and 2019. The MNT was carried out for all COVID-19 samples (70 serum samples, 62 individuals) and for 53 samples from the negative panel. Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). This study shows variable performance values. Laboratories should carefully consider their testing process, such as a two-tier approach, in order to optimize the overall performance of SARS- CoV-2 serodiagnostics. url: https://www.sciencedirect.com/science/article/pii/S1386653220302547?v=s5 doi: 10.1016/j.jcv.2020.104512 id: cord-350505-uh8r2vyz author: Kalantar-Zadeh, Kourosh title: Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles date: 2020-05-01 words: 2343.0 sentences: 145.0 pages: flesch: 38.0 cache: ./cache/cord-350505-uh8r2vyz.txt txt: ./txt/cord-350505-uh8r2vyz.txt summary: [Image: see text] The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. 2 Therefore, the elucidation of host cytokine molecular pathways and microbiota components 17 as well as bacterial reactions in association with cytokine responses may provide novel microbiome-based therapeutic approaches to SARS-CoV-2 infection. Considering the presented discussion, nutritional and dietary strategies directed at restoring the well-known beneficial microbiota, which can possibly suppress viral infection in the elderly and those with underlying health problems, may be an effective strategy to mitigate the harmful effects of this virus. One approach, as a whole and to be undertaken prior to any viral infection, could include strengthening the intestinal barrier against pathogens, increasing intestinal motility, and reducing an underlying pro-inflammatory state by adopting a Many different direct or indirect microbiome pathways could contribute to SARS-CoV-2-gut interactions. abstract: [Image: see text] The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. In this Perspective, we present a rationale for an urgent need to investigate this possible impact and therapeutic options for COVID-19 based on dietary and microbiome modifications. The mitigating role of nanotechnology with relation to the impact of SARS-CoV-2 virus is highlighted. url: https://www.ncbi.nlm.nih.gov/pubmed/32356654/ doi: 10.1021/acsnano.0c03402 id: cord-292025-dr611nse author: Kam, Kai-qian title: Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children date: 2020-06-13 words: 1648.0 sentences: 104.0 pages: flesch: 52.0 cache: ./cache/cord-292025-dr611nse.txt txt: ./txt/cord-292025-dr611nse.txt summary: From 23 March 2020 to 3 April 2020, all inpatient pediatric confirmed COVID-19 cases diagnosed via positive SARS-CoV-2 polymerase chain reaction (PCR) from nasopharyngeal swabs using the real-time reverse transcription (rRT)-PCR assay for the E gene were included in this study. In the 9 infected children with detectable SARS-CoV-2 in buccal specimens, the mean difference of Ct values between buccal and nasopharyngeal specimens for all infected patients was 10.7 (range, 6.1-16.1), and this was statistically significant (P < .001). Our findings confirm that SARS-CoV-2 can be detected in buccal specimens of infected children and that the viral load is the highest in the first week of illness or diagnosis. In our study, the average viral loads of buccal SARS-CoV-2 were consistently lower than the respective nasopharyngeal specimens, with substantial differences between the average Ct values. Two COVID-19-infected children had negative buccal specimens despite detectable nasopharyngeal viral load. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)–infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children. url: https://doi.org/10.1093/jpids/piaa068 doi: 10.1093/jpids/piaa068 id: cord-347351-emdj66vj author: Kampf, Günter title: Potential sources, modes of transmission and effectiveness of prevention measures against SARS-CoV-2 date: 2020-09-18 words: 10283.0 sentences: 592.0 pages: flesch: 50.0 cache: ./cache/cord-347351-emdj66vj.txt txt: ./txt/cord-347351-emdj66vj.txt summary: Originating from a single travel-associated primary case from China, the first documented chain of multiple human-to-human transmissions of SARS-CoV-2 outside of Asia allowed a detailed study of transmission events and identified several factors (e.g. cumulative face-toface contact, direct contact with secretions or body fluids of a patient, personal protective equipment) to classify contacts as low or high risk [32] . In the close surrounding of COVID-19 patients in hospitals SARS-CoV-2 RNA is detected more frequently compared to surfaces outside the patient rooms but samples were so far consistently negative for infectious virus. General disinfection of frequently touched surfaces in the public such as shopping carts or door handles is, however, unlikely to add any protective value because even in COVID-19 wards inanimate surfaces were mainly contaminated in the permanent and immediate surrounding of symptomatic patients (detection of viral RNA, not of infectious virus) and only rarely one room away [138] suggesting that the risk to find SARS-CoV-2 on frequently touched surfaces in the public is low. abstract: During the current SARS-CoV-2 pandemic new studies are emerging daily providing novel information about sources, transmission risks and possible prevention measures. In this review, we aimed to comprehensively summarize the current evidence on possible sources for SARS-CoV-2, including evaluation of transmission risks and effectiveness of applied prevention measures. Next to symptomatic patients, asymptomatic or pre-symptomatic carriers are a possible source with respiratory secretions as the most likely cause for viral transmission. Air and inanimate surfaces may be sources; however, viral RNA has been inconsistently detected. Similarly, even though SARS-CoV-2 RNA has been detected on or in personnel protective equipment, blood, urine, eyes, the gastrointestinal tract and pets, these sources are currently thought to play a negligible role for transmission. Finally, various prevention measures such as hand washing, hand disinfection, face masks, gloves, surface disinfection or physical distancing for the healthcare setting and public are analysed for their expected protective effect. url: https://doi.org/10.1016/j.jhin.2020.09.022 doi: 10.1016/j.jhin.2020.09.022 id: cord-338468-c0jv3i1t author: Kanduc, Darja title: From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry date: 2020-07-16 words: 4143.0 sentences: 234.0 pages: flesch: 41.0 cache: ./cache/cord-338468-c0jv3i1t.txt txt: ./txt/cord-338468-c0jv3i1t.txt summary: Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. In the wake of such results, in order to validate (or, as well, invalidate) the cross-reactivity hypothesis, investigation was expanded here by analyzing the peptide sharing between the human host and immunoreactive epitopes that are also present in SARS-CoV-2. Table 2 documents that numerous immunoreactive SARS-CoV-2 epitopes are composed mostly or, in many instances, uniquely of peptide sequences shared with human proteins. This study shows that hexapeptides from immunoreactive epitopes present in SARS-CoV-2 are widespread among a high number of human proteins. Table S2 : Hexapeptide sharing between 233 epitopes present in SARS-CoV-2 and human proteins. Table S3 : List and short description of 460 human proteins that share hexapeptides with the 233 SARS-CoV-2 epitopes. abstract: Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic. url: https://doi.org/10.3390/antib9030033 doi: 10.3390/antib9030033 id: cord-310807-p5cb6idp author: Kanwar, Anubhav title: Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio date: 2017-03-25 words: 2944.0 sentences: 176.0 pages: flesch: 46.0 cache: ./cache/cord-310807-p5cb6idp.txt txt: ./txt/cord-310807-p5cb6idp.txt summary: Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. In this study, we report one of the largest case series of CoV-HKU1 infections among adults presenting with respiratory tract illness and describe their clinical characteristics. Clinical data analysis for adults (patients >18 years of age) included the following: age, gender, hospitalization status, length of hospitalization, clinical features, discharge diagnosis, outcome (death or survived), comorbidities (smoking, lung disease), laboratory and radiology results, intensive care unit (ICU) stay, oxygen use and duration, treatment provided, and exposure history. Similar studies describing HKU1 in pediatric and adult patients have also found an association with upper and lower respiratory tract illness [7, 9, 12, 15, 21] . Our study provides needed insight into clinical characteristics and severity associated with CoV-HKU1 infection in adults in the Northeast region of the United States. abstract: BACKGROUND. Human coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness. Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. METHODS. Nasopharyngeal specimens of patients with respiratory symptoms were analyzed for CoV-HKU1 by NxTAG Respiratory Pathogen Panel multiplex assay from February 7, 2016 to April 30, 2016. Epidemiologic, clinical, and laboratory data were collected on adults (patients >18 years) whose samples screened positive. RESULTS. Of 832 adult respiratory specimens screened, 13 (1.6%) cases of CoV-HKU1 were identified. Adults age ranged between 23 and 75 years and 6 (46%) were males. All of whom had 1 or more respiratory symptoms, and 5 (38%) also reported 1 or more gastrointestinal symptoms. Eleven (85%) reported history of smoking and 5 (38%) used inhaled steroids. Seven (54%) required hospitalization, 5 (71%) of these needed supplemental oxygen, and 2 (29%) were admitted to intensive care. Median length of hospitalization was 5 days. Eight (62%) received antibiotics despite identification of CoV-HKU1. Infectious work-up in 1 patient who died did not reveal any other pathogen. In 2 (15%) CoV-HKU1-positive adults, the only viral coinfection detected was influenza A. CONCLUSIONS. Coronavirus-HKU1 accounted for 1.6% of adult respiratory infections and should be considered in differential diagnosis of severe respiratory illnesses among adults. url: https://www.ncbi.nlm.nih.gov/pubmed/28616442/ doi: 10.1093/ofid/ofx052 id: cord-270396-3bcnnyfq author: Karacin, Cengiz title: How does COVID-19 fear and anxiety affect chemotherapy adherence in patients with cancer date: 2020-07-17 words: 3605.0 sentences: 177.0 pages: flesch: 57.0 cache: ./cache/cord-270396-3bcnnyfq.txt txt: ./txt/cord-270396-3bcnnyfq.txt summary: Aim: To investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy adherence in patients with cancer. Data on patients'' age, sex, comorbidities, history of smoking, marital status, number of children, educational background, place of residence and household, cancer type, disease stage, CT regimen and date of CT postponement were obtained from the hospital records. In the present study, it was seen that the CT postponement rate increased significantly following the first COVID-19 case in Turkey and COV-FA was identified as the third most frequent reason for CT postponement. In the present study, the median TCBT of the patients who postponed CT due to COV-FA was 47 days (range . • We aimed to investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy (CT) adherence in patients receiving active CT for cancer, and to identify the characteristics of patients who postponed their CT due to COV-FA, as well as the time to come back to treatment (TCBT) and the factors affecting TCBT in these patients. abstract: Aim: To investigate how COVID-19 fear and anxiety (COV-FA) affects chemotherapy adherence in patients with cancer. Materials & methods: The records of 3661 patients with chemotherapy (CT) appointments were retrospectively reviewed. Results: The CT postponement rates before and after COVID-19 were 11.6% and 14.2%, respectively (p = 0.017). The rate of COV-FA-related CT postponement after telemedicine was lower than that before (4.6% vs 17.4%, p = 0.012). The median time to come back to treatment of the COV-FA group was 47 days (range 19–72 days). Advanced age (≥60 years) was found to be the independent factor that was predictive of time to come back to treatment (p = 0.043). Conclusion: The CT postponement rate increased after COVID-19. COV-FA-related CT postponement decreased after telemedicine. Advanced age could be predictive of time to come back to treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/32677462/ doi: 10.2217/fon-2020-0592 id: cord-331039-qgom2e3n author: Kavitha, Kuppuswamy title: 1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates date: 2020-09-22 words: 4929.0 sentences: 326.0 pages: flesch: 57.0 cache: ./cache/cord-331039-qgom2e3n.txt txt: ./txt/cord-331039-qgom2e3n.txt summary: A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 M(pro) and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. The objectives of this study were i) to identify evolutionarily important active site amino acids by structure-based sequence alignment of SARS-CoV-2 and SARS-CoV M pro enzymes ii) to identify potential non-covalent M pro inhibitors by screening protease-inhibitor-like compounds available in the ZINC database by molecular docking studies iii) prediction of absorption, distribution metabolism, excretion and toxicity properties of the top-scoring inhibitors using in silico methods iv) to validate the stable binding of the lead compounds with SARS-CoV-2 M pro by molecular dynamics (MD) simulations and v) to calculate thermodynamic binding energies for each lead compound -SARS-CoV-2 M pro complex using Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations. abstract: Discovery of a potent SARS-CoV-2 main protease (M(pro)) inhibitor is the need of the hour to combat COVID-19. A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 M(pro) and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. We report these two compounds (ZINC000621278586 and ZINC000621285995) as potent SARS-CoV-2 M(pro) inhibitors with high affinity (<−9 kCal/mol) and less toxicity than Lopinavir and Nelfinavir positive controls. Both the lead compounds effectively interacted with the crucial active site amino acid residues His41, Cys145 and Glu166. The lead compounds satisfied all of the druglikeness rules and devoid of toxicity or mutagenicity. Molecular dynamics simulations showed that both lead 1 and lead 2 formed stable complexes with SARS-CoV-2 M(pro) as evidenced by the highly stable root mean square deviation (<0.23 nm), root mean square fluctuations (0.12 nm) and radius of gyration (2.2 nm) values. Molecular mechanics Poisson-Boltzmann surface area calculation revealed thermodynamically stable binding energies of −129.266 ± 2.428 kJ/mol and − 116.478 ± 3.502 kJ/mol for lead1 and lead2 with SARS-CoV-2 M(pro), respectively. url: https://www.sciencedirect.com/science/article/pii/S0301462220301861?v=s5 doi: 10.1016/j.bpc.2020.106478 id: cord-330343-p7a8chn4 author: Kelly-Cirino, Cassandra title: An updated roadmap for MERS-CoV research and product development: focus on diagnostics date: 2019-02-01 words: 5812.0 sentences: 274.0 pages: flesch: 40.0 cache: ./cache/cord-330343-p7a8chn4.txt txt: ./txt/cord-330343-p7a8chn4.txt summary: ► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. abstract: Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management. url: https://doi.org/10.1136/bmjgh-2018-001105 doi: 10.1136/bmjgh-2018-001105 id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic. url: https://doi.org/10.3389/fimmu.2020.570927 doi: 10.3389/fimmu.2020.570927 id: cord-278362-pwi48i20 author: Khan, Abbas title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) date: 2020-06-18 words: 5136.0 sentences: 287.0 pages: flesch: 55.0 cache: ./cache/cord-278362-pwi48i20.txt txt: ./txt/cord-278362-pwi48i20.txt summary: title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro) Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. In this study, the protein of SARS-COV-2 (3CLpro, also named 3-chymotrypsin-like protease) was subjected to drug repurposing and virtual screening for potent drug identification followed by molecular dynamics simulation and binding free energy calculation. In the current study, the repurposing of anti-HIV drugs against the SARS-COV-2 main protease was carried out using structure-based screening methods. In this study, based on the results of bioinformatics analysis, we targeted 3CLpro from SARS-COV-2 using drugs repurposing (anti-HIV drugs) virtual drugs screening (TCM) approaches to shortlist the most potent compounds for the possible treatment. abstract: The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma. url: https://doi.org/10.1080/07391102.2020.1779128 doi: 10.1080/07391102.2020.1779128 id: cord-304792-8sdxqmkb author: Khan, Md. Abdullah-Al-Kamran title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 words: 2983.0 sentences: 207.0 pages: flesch: 48.0 cache: ./cache/cord-304792-8sdxqmkb.txt txt: ./txt/cord-304792-8sdxqmkb.txt summary: title: SARS-CoV-2 proteins exploit host''s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. We have utilized KEGG mapper tool (Kanehisa and Sato, 2020) for the mapping of 197 deregulated genes SARS-CoV-2 interacting host proteins in different cellular pathways. abstract: The constant rise of the death toll and cases of COVID-19 has made this pandemic a serious threat to human civilization. Understanding of host-SARS-CoV-2 interaction in viral pathogenesis is still in its infancy. In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. We have utilized a blend of computational and knowledgebase approach to elucidate the interplay between host and SARS-CoV-2. Integrating the experimentally validated host interactome proteins and differentially expressed host genes due to SARS-CoV-2 infection, we have taken a blend of computational and knowledgebase approach to delineate the interplay between host and SARS-CoV-2 in various signaling pathways. Also, we have shown how host epigenetic factors are involved in the deregulation of gene expression. Strikingly, we have found that several transcription factors and other epigenetic factors can modulate some immune signaling pathways, helping both host and virus. We have identified miRNA hsa-miR-429 whose transcription factor was also upregulated and targets were downregulated and this miRNA can have pivotal role in suppression of host immune responses. While searching for the pathways in which viral proteins interact with host proteins, we have found pathways like-HIF-1 signaling, autophagy, RIG-I signaling, Toll-like receptor signaling, Fatty acid oxidation/degradation, Il-17 signaling etc significantly associated. We observed that these pathways can be either hijacked or suppressed by the viral proteins, leading to the improved viral survival and life-cycle. Moreover, pathways like-Relaxin signaling in lungs suggests aberration by the viral proteins might lead to the lung pathophysiology found in COVID-19. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. might suggest why patients with comorbidities are becoming more prone to SARS-CoV-2 infection. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. Our findings would help in designing more targeted therapeutic interventions against SARS-CoV-2. url: https://doi.org/10.1101/2020.05.06.050260 doi: 10.1101/2020.05.06.050260 id: cord-346819-11fkgzaa author: Khan, Mohd Imran title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight date: 2020-09-03 words: 4405.0 sentences: 291.0 pages: flesch: 57.0 cache: ./cache/cord-346819-11fkgzaa.txt txt: ./txt/cord-346819-11fkgzaa.txt summary: title: Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. The genome analysis of the SARS-CoV-2 strains from 13 different countries showed a large number of mutations within the major structural proteins. This study provides a deeper insight into the emergence of these mutations within the major structural as well as nsp encoded by the SARS-CoV-2 genome from different countries. Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations backbone RMSD was also noticed (Fig 4A) . abstract: A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19. url: https://www.ncbi.nlm.nih.gov/pubmed/32881907/ doi: 10.1371/journal.pone.0238344 id: cord-304295-3mpymd8a author: Khan, Muhammad Muzamil title: Emergence of novel coronavirus and progress toward treatment and vaccine date: 2020-06-04 words: 2935.0 sentences: 210.0 pages: flesch: 48.0 cache: ./cache/cord-304295-3mpymd8a.txt txt: ./txt/cord-304295-3mpymd8a.txt summary: 10 Favipiravir was effectively used against influenza and has the potential to inhibit viral RNA synthesis and a new study also supports its activity against SARS-CoV-2. 15 In another recent study, Gao et al found that chloroquine phosphate reduced the symptoms of pneumonia in SARS-CoV-2 patients and shortening the duration of disease. 67 Different technologies are being utilized to F I G U R E 1 Mechanism of action of HCQ and CQ by blocking binding of virus with ACE-2 receptors and increasing endosomal pH and preventing fusion with the cell develop potential vaccine for SARS-CoV-2 including DNA and mRNAbased nanoparticles. Clinical study for safety and efficacy of favipiravir in the treatment of novel coronavirus pneumonia (COVID-19) In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) abstract: In late December 2019, a group of patients was observed with pneumonia‐like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS‐CoV‐2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS‐CoV‐2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines. url: https://doi.org/10.1002/rmv.2116 doi: 10.1002/rmv.2116 id: cord-279443-2e4gz2bo author: Khan, Suliman title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns date: 2020-06-09 words: 4939.0 sentences: 245.0 pages: flesch: 43.0 cache: ./cache/cord-279443-2e4gz2bo.txt txt: ./txt/cord-279443-2e4gz2bo.txt summary: To identify and select the papers in this review we searched the published research and review articles relevant to origin and outbreaks of three human coronaviruses, and features, transmission, spread, entry mechanisms, infectiousness, control strategies, and animals hosts for SARS-CoV-2. Although it is important to know about the symptoms'' appearance and severity, however, understanding the transmission of the infection to healthy individuals from COVID-19 patients and zoonotic sources can be of great importance in the aspects of developing strategies to prevent and control the spread of COVID-19. This outbreak was reported to be caused by SARS-CoV, originated from market civets before its transmission and infection in humans (17) . Early claims came FIGURE 2 | The SARS-CoV-2 transmission from bats via unknown intermediate to humans causes infectiousness known as COVID-19 disease. According to the CDC report on coronavirus disease, individuals with underlying chronic medical conditions are at higher risk for contracting COVID-19 infection. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal–oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak. url: https://doi.org/10.3389/fmed.2020.00310 doi: 10.3389/fmed.2020.00310 id: cord-309138-44qpk2vf author: Khanna, Kanika title: Herbal Immune-boosters: Substantial Warriors of Pandemic Covid-19 Battle date: 2020-10-03 words: 6385.0 sentences: 354.0 pages: flesch: 43.0 cache: ./cache/cord-309138-44qpk2vf.txt txt: ./txt/cord-309138-44qpk2vf.txt summary: Moreover, AYUSH has recommended certain preventive and medicinal plants for prevention and prophylactic of COVID-19 including warm extracts of Tinospora cordifolia (advised for chronic fever), Andrograhis paniculata (advised for fever and cold), Cydonia oblonga, Zizyphus jujube and Cordia myxa (enhancing antioxidant, immune-modulatory, anti-allergic, smooth muscle relaxant, anti-influenza activity) and Ever since, has been elucidated that, PAK1 tends to cause cancers, viral diseases like HIV, Hepatitis, pappiloma, influenza, ebola, SARS and corona virus along with immune system suppression of hosts, henceforth, propolis would be quintessential in blocking COVID/coronavirus curbed fibrosis in respiratory tract and boosting the immunity of an individual (Maruta, 2014) . Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: A systematic review Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective abstract: Current scenario depicts that world has been clenched by COVID-19 pandemic. Inevitably, public health and safety measures could be undertaken in order to dwindle the infection threat and mortality. Moreover, to overcome the global menace and drawing out world from moribund stage, there is an exigency for social distancing and quarantines. Since December, 2019, coronavirus, SARS-CoV-2 (COVID-19) have came into existence and up till now world is still in the state of shock.At this point of time, COVID-19 has entered perilous phase, creating havoc among individuals, and this has been directly implied due to enhanced globalisation and ability of the virus to acclimatize at all conditions. The unabated transmission is due to lack of drugs, vaccines and therapeutics against this viral outbreak. But research is still underway to formulate the vaccines or drugs by this means, as scientific communities are continuously working to unravel the pharmacologically active compounds that might offer a new insight for curbing infections and pandemics. Therefore, the topical COVID-19 situation highlights an immediate need for effective therapeutics against SARS-CoV-2. Towards this effort, the present review discusses the vital concepts related to COVID-19, in terms of its origin, transmission, clinical aspects and diagnosis. However, here, we have formulated the novel concept hitherto, ancient means of traditional medicines or herbal plants to beat this pandemic. url: https://api.elsevier.com/content/article/pii/S0944711320301926 doi: 10.1016/j.phymed.2020.153361 id: cord-323061-0i5w7vm9 author: Kharel Sitaula, Ranju title: Unfolding COVID-19: Lessons-in-Learning in Ophthalmology date: 2020-09-28 words: 4845.0 sentences: 266.0 pages: flesch: 51.0 cache: ./cache/cord-323061-0i5w7vm9.txt txt: ./txt/cord-323061-0i5w7vm9.txt summary: 10 Epiphora and Conjunctival redness had been the first manifestation of SARS-CoV-2 infection in 3 reported cases till date which includes a member of National expert on pneumonia during his visit to endemic areas of Wuhan and an anesthesiologist contracting the virus from a known patient of novel coronavirus pneumonia during intubation in Italy; similarly, it was reported in a nurse working in the emergency department of ophthalmology who presented with viral conjunctivitis and watering as a first sign. Hence, our knowledge and understanding about the SARS-CoV-2 virus, modes of entry to the eye, hypothesis on the interaction with the Renin-Angiotensin System (RAS) system and ACE2 receptor and ocular pathogenesis and RT PCR analysis from the ocular secretions have been summarized below using text, tables, diagrams, and flowcharts. abstract: IMPORTANCE: An observant Chinese doctor Li Wenliang became the first physician to alert the world about COVID-19. Being an ophthalmologist himself, he has put the additional onus on us. The fact that the ocular manifestation could be the first presenting feature of novel coronavirus pneumonia should not be ignored and the possibility of spread of SARS-CoV-2 through the ocular secretions cannot be ruled out. However, with breakthroughs still evolving about this disease, the calls are now louder for closer examination on the pathogenesis of conjunctivitis associated with it. Hence, we conducted a scoping review of all available literature till date to fill in the “potential” gaps in currently available knowledge on ocular manifestations of SARS-CoV-2 infection in an attempt to establish continuity in the “chain of information” from December 2019 till April 2020. We also summarize a possible hypothesis on much less understood and highly debated topics on regard to the etiopathogenesis of ocular involvement in SARS-CoV-2 based on either presence or absence of ACE2 receptor in the ocular surface. METHODS: We conducted a scoping review search of published and unpublished SARS-CoV-2-related English language articles from December 2019 till mid of April 2020 from the online databases. The findings were summarized using text, tables, diagrams, and flowcharts. RESULTS: The commonest ocular manifestation in SARS-CoV-2 infection is follicular conjunctivitis and has been the first manifestation of SARS-CoV-2 infection in 3 reported cases till date. The ocular surface inoculated with the SARS-CoV-2 leads to the facilitation of the virus to the respiratory system via the lacrimal passage. RT-PCR analysis of the ocular secretions has shown the presence of the SARS-CoV-2 nucleotides indicating the possibility of infection of ocular secretions. ACE2 receptors and its expression on the ocular mucosal surface are linked behind the etiopathogenesis of conjunctivitis. CONCLUSION: Conjunctivitis can be the presenting manifestation but may go unnoticed due to its mild nature. The ocular surface could serve as the entry gateway for the virus and ocular secretions could play a role in virus shed. The eye care personnel, as well as the general people, need to be more vigilant and adopt protective eye measures. url: https://doi.org/10.2147/opth.s259857 doi: 10.2147/opth.s259857 id: cord-306581-g3d0lqxp author: Khattab, Mohamed H. title: Early detection of SARS-CoV-2 from staging PET-CT date: 2020-09-29 words: 1214.0 sentences: 78.0 pages: flesch: 45.0 cache: ./cache/cord-306581-g3d0lqxp.txt txt: ./txt/cord-306581-g3d0lqxp.txt summary: METHODS: Here, we present a case study of a mildly symptomatic patient with anal cancer diagnosed with SARS-CoV-2 from a staging PET-CT scan. Given the ongoing COVID-19 pandemic, a nasopharyngeal swab with polymerase chain reaction (PCR) was obtained and was confirmed positive for the potentially lethal SARS-CoV-2 viral infection. In geographic regions with a Fig. 1 Screening positron emission tomography fused with computed tomography demonstrating fluorodeoxyglucose-avid multifocal, rounded, peripheral ground-glass nodules, some demonstrating the reversed halo sign, within the right lower, right middle, and left lower lung lobes concerning for an infectious process significant and increasing COVID-19 case burden, routine PCR testing in the absence of clinical or radiologic findings may be indicated in patients undergoing chemoradiation or radiation, and it is our institutional practice to test all patients receiving any chemotherapy or greater than 10 days of radiation. In the setting of asymptomatic or mildly symptomatic patients with confirmed SARS-CoV-2 infection, multidisciplinary discussion with oncology and infectious disease teams is important to ascertain the risks and benefits of delaying cancer therapy. abstract: OBJECTIVE: SARS-CoV-2 infection may manifest with minimal or no clinical symptoms. However, signs of infection may appear on routine imaging obtained in the care of patients with cancer. The management of patients planned for chemoradiation with asymptomatic or mildly symptomatic SARS-CoV-2 infection is uncertain. METHODS: Here, we present a case study of a mildly symptomatic patient with anal cancer diagnosed with SARS-CoV-2 from a staging PET-CT scan. RESULTS: PET-CT scan for anal cancer staging demonstrated pulmonary avidity suspicious for an infectious, rather than malignant, process. In the setting of these imaging findings and new-onset anosmia, viral polymerase chain reaction was ordered and found to be positive for SARS-CoV-2. To avoid myelosuppression in the setting of active infection, planned chemoradiation was delayed until cessation of viral shedding. CONCLUSION: In the COVID-19 era, oncologists obtaining routine staging imaging should have high diagnostic suspicion for subclinical SARS-CoV-2 infection. To avoid precipitating severe pneumonia and hospitalization, multidisciplinary discussion with risk-benefit analysis is recommended before initiating immunosuppressive therapies such as chemoradiation. url: https://doi.org/10.1007/s13566-020-00436-w doi: 10.1007/s13566-020-00436-w id: cord-343196-vlwzzrgc author: Kiambi, Stella title: Detection of distinct MERS-Coronavirus strains in dromedary camels from Kenya, 2017 date: 2018-11-28 words: 1494.0 sentences: 71.0 pages: flesch: 50.0 cache: ./cache/cord-343196-vlwzzrgc.txt txt: ./txt/cord-343196-vlwzzrgc.txt summary: The MERS-CoV RNA-positive animals belonged to two different dromedary camel herds in Dabel and Lombolio, which are both located within Isiolo country. To experimentally confirm the presence of two independently circulating MERS-CoV strains and to rule out sample cross-contamination, we generated complete MERS-CoV genome sequences using a previously established protocol 10 . Other confirmed MERS-CoVpositive samples were assigned to two different MERS-CoV isolates ("Dabel" or "Lombolio") by amplifying and sequencing single-nucleotide polymorphisms in the spike gene and the open reading frame 3 (Supplementary Table) . The previously described clade C African MERS-CoV strains 4,5 had several mutations in the spike protein, which is responsible for cellular receptor interaction, virus entry, and antibody-directed virus neutralization 12 . An explanation for this observation may again be a lack of testing of imported animals and/or the fact that previous clade A/B MERS-CoV infections may have established herd immunity in the Arabian dromedary populations. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/30482895/ doi: 10.1038/s41426-018-0193-z id: cord-336775-d4hi9myk author: Kirtipal, Nikhil title: From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses date: 2020-08-13 words: 8606.0 sentences: 442.0 pages: flesch: 46.0 cache: ./cache/cord-336775-d4hi9myk.txt txt: ./txt/cord-336775-d4hi9myk.txt summary: Abstract Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – diseases termed as COVID-19. Hence, acute respiratory distress syndrome (ARDS) is caused by cytokine storm that triggers a destruction in host cells via immune system and subsequently results into multiple organs failure or death as stated in case of SARS-CoV-2 outbreak; similar observations were noted in case of SARS-CoV infection (Kumar et al., 2020) . When developing novel therapeutic strategies to check the immunoregulatory cytokines such as TNFβ and IL6, investigation should be considered on the viral strain and targeted organ specificity; for example, SARS-CoV-2 has more affinity to ACE2 which are scattering on different organs like lung and kidney while MERS-like CoV can even infect T-cells. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) abstract: Abstract Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – diseases termed as COVID-19. Current SARS-CoV-2 outbreak have fueled ongoing efforts to exploit various viral target proteins for therapy, but strategies aimed at blocking the viral proteins as in drug and vaccine development have largely failed. In fact, evidence has now shown that coronaviruses undergoes repaid recombination to generate new strains of altered virulence; additionally, escaped the host antiviral defense system and target humoral immune system which further results in severe deterioration of the body such as by cytokine storm. This demands the understanding of phenotypic and genotypic classification, and pathogenesis of SARS-CoV-2 for the production of potential therapy. In lack of clear clinical evidences for the pathogenesis of COVID-19, comparative analysis of previous pandemic HCoVs associated immunological responses can provide insights into COVID-19 pathogenesis. In this Review, we summarize the possible origin and transmission mode of CoVs and the current understanding on the viral genome integrity of known pandemic virus against SARS-CoV-2. We also consider the host immune response and viral evasion based on available clinical evidences which would be helpful to remodel COVID-19 pathogenesis; and hence, development of therapeutic against broad spectrum of coronaviruses. url: https://doi.org/10.1016/j.meegid.2020.104502 doi: 10.1016/j.meegid.2020.104502 id: cord-264267-weat0qs6 author: Kleine-Weber, Hannah title: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus date: 2020-01-21 words: 7200.0 sentences: 325.0 pages: flesch: 47.0 cache: ./cache/cord-264267-weat0qs6.txt txt: ./txt/cord-264267-weat0qs6.txt summary: Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. For host cell entry, the surface unit, S1, of MERS-CoV S binds to the cellular type-II transmembrane protein dipeptidyl peptidase 4 (DPP4, CD26) [15] . For the binding studies with solMERS-S1-Fc, a similar protocol was followed as described for the analysis of DPP4 surface expression with the exceptions that sol-MERS-S1-Fc was used instead of the primary antibody (1:10 dilution in PBS/BSA) and that an AlexaFluor488conjugated anti-human antibody (goat, 1:500 dilution in PBS/BSA, ThermoFisher Scientific) was employed as the secondary antibody. Reduced MERS-CoV S-driven host cell entry is caused by inefficient S protein binding to DPP4 harboring polymorphic amino acid residues. abstract: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients. url: https://doi.org/10.1080/22221751.2020.1713705 doi: 10.1080/22221751.2020.1713705 id: cord-300968-dtaasxk1 author: Kliger, Yossef title: From genome to antivirals: SARS as a test tube date: 2005-03-01 words: 5104.0 sentences: 272.0 pages: flesch: 46.0 cache: ./cache/cord-300968-dtaasxk1.txt txt: ./txt/cord-300968-dtaasxk1.txt summary: Abstract The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. This strategy seems promising in developing anti-viral therapeutic peptides to other viruses that possess type 1 viral fusion proteins [e.g. measles virus and respiratory syncytial virus (RSV)], which share some structural motifs with HIV. Similar to HIV, binding of the viral spike glycoprotein to some receptor(s) on host cells is the first step in SARS-CoV infection. HIV entry involves the binding of the viral envelope glycoproteins (comprising gp120 and gp41, which are the homologous of SARS-CoV S1 and S2, respectively) to CD4 on the host cell plasma membrane. Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoproteinmediated viral entry Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeatderived peptides abstract: Abstract The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/15749283/ doi: 10.1016/s1359-6446(04)03320-3 id: cord-345381-9cckppk2 author: Klimek, Ludger title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) date: 2020-09-07 words: 6146.0 sentences: 332.0 pages: flesch: 43.0 cache: ./cache/cord-345381-9cckppk2.txt txt: ./txt/cord-345381-9cckppk2.txt summary: title: Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)(A), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)(B), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)(C), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)(D), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)(E), Österreichische Gesellschaft für Pneumologie (ÖGP)(F) in co-operation with the German, Austrian, and Swiss ARIA groups(G), and the European Academy of Allergy and Clinical Immunology (EAACI)(H) Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontane-ous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. abstract: Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for “social distancing” and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. Materials and methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 – April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients. url: https://doi.org/10.5414/alx02166e doi: 10.5414/alx02166e id: cord-267770-ik1ib3zb author: Koo, Hyun Jung title: RadioGraphics Update: Radiographic and CT Features of Viral Pneumonia date: 2020-06-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Editor’s Note.—Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article. url: https://www.ncbi.nlm.nih.gov/pubmed/32501740/ doi: 10.1148/rg.2020200097 id: cord-323905-ayufx3wv author: Kort, N. P. title: Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members date: 2020-08-18 words: 3708.0 sentences: 225.0 pages: flesch: 53.0 cache: ./cache/cord-323905-ayufx3wv.txt txt: ./txt/cord-323905-ayufx3wv.txt summary: title: Recommendations for resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: the European Hip Society and European Knee Associates Survey of Members The April 2020 SARS-CoV-2 survey completed by EHS and EKA members in Europe has confirmed the impact of SARS-CoV-2: this pandemic has resulted in a tremendous reduction in primary hip and knee arthroplasty procedures as shown in the survey. The benefits of hip and knee arthroplasty should be carefully weighed against the risks of viral transmission and infection, complications and mortality in the mostly elderly population requiring joint arthroplasty Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: pre-operative phase 1. Is there a need for -Modification or reorganization of hospital wards (patient density, bed density, medical and nursing stuff density, etc.)?417 (81) 70 (14) Resuming elective hip and knee arthroplasty in the setting of the SARS-CoV-2 pandemic: post-operative phase 1. abstract: PURPOSE: The COVID-19 pandemic has disrupted the health care system around the entire globe. A consensus is needed about resuming total hip and knee procedures. The European Hip Society (EHS) and the European Knee Association (EKA) formed a panel of experts that have produced a consensus statement on how the safe re-introduction of elective hip and knee arthroplasty should be undertaken. METHODS: A prospective online survey was done among members of EHS and EKA. The survey consisted of 27 questions. It includes basic information on demographics and details the participant’s agreement with each recommendation. The participant could choose among three options (agree, disagree, abstain). Recommendations focussed on pre-operative, peri-operative, and post-operative handling of patients and precautions. RESULTS: A total of 681 arthroplasty surgeons participated in the survey, with 479 fully completing the survey. The participants were from 44 countries and 6 continents. Apart from adhering to National and Local Guidelines, the recommendations concerned how to make elective arthroplasty safe for patients and staff. CONCLUSION: The survey has shown good-to-excellent agreement of the participants with regards to the statements made in the recommendations for the safe return to elective arthroplasty following the first wave of the COVID-19 pandemic. url: https://doi.org/10.1007/s00167-020-06212-0 doi: 10.1007/s00167-020-06212-0 id: cord-321624-z2mntwef author: Kowitdamrong, Ekasit title: Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019 date: 2020-10-09 words: 3382.0 sentences: 184.0 pages: flesch: 57.0 cache: ./cache/cord-321624-z2mntwef.txt txt: ./txt/cord-321624-z2mntwef.txt summary: AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. The objective of this study was to investigate the response of IgA and IgG antibodies to SARS--CoV-2 in serial blood samples collected from a population of Thai patients with confirmed COVID-19, and the association of these responses with the severity of the illness. The second subgroup included 49 plasma samples collected from May 1 to May 31, 2020, from patients under investigation (PUI) for COVID-19 with RT-PCR results that were negative for SARS-CoV-2. In the present study, 30% of COVID-19 patients developed positive IgA antibodies very early, within 3 days after the onset of symptoms. In the present study, 20% of the patients with mild symptoms did not develop any IgG antibodies specific to COVID-19, even after 2 weeks after the onset of symptoms. abstract: BACKGROUND: A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. METHODS: Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. RESULTS: A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8–93.6) and 84.8% (95% CI: 76.2–91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). CONCLUSION: The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection. url: https://www.ncbi.nlm.nih.gov/pubmed/33035234/ doi: 10.1371/journal.pone.0240502 id: cord-333703-1ku3jc9s author: Kraus, Aurora title: A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date: 2020-11-08 words: 8452.0 sentences: 605.0 pages: flesch: 57.0 cache: ./cache/cord-333703-1ku3jc9s.txt txt: ./txt/cord-333703-1ku3jc9s.txt summary: Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. In mice and humans, ace2 expression is detected in 121 sustentacular cells, olfactory stem cells known as horizontal and globose basal cells in the 122 olfactory epithelium, and vascular cells (pericytes) in the olfactory bulb (Brann et al., 2020 The present study reports for the first time that zebrafish larvae exposed to SARS-CoV-2 appear 134 to mount innate immune responses that resemble cytokine responses of mild COVID-19 patients. There are copious amounts of immune cells in the teleost olfactory organ ( Intranasal delivery of SARS-CoV-2 S RBD induces inflammatory responses and 318 widespread loss of olfactory receptor expression in adult zebrafish olfactory organ 319 320 abstract: The COVID-19 pandemic has prompted the search for animal models that recapitulate the pathophysiology observed in humans infected with SARS-CoV-2 and allow rapid and high throughput testing of drugs and vaccines. Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. Intranasal administration of SARS-CoV-2 S RBD in adult zebrafish recombinant protein caused severe olfactory and mild renal histopathology. Zebrafish intranasally treated with SARS-CoV-2 S RBD became hyposmic within minutes and completely anosmic by 1 day to a broad-spectrum of odorants including bile acids and food. Single cell RNA-Seq of the adult zebrafish olfactory organ indicated widespread loss of expression of olfactory receptors as well as inflammatory responses in sustentacular, endothelial, and myeloid cell clusters. Exposure of wildtype zebrafish larvae to SARS-CoV-2 in water did not support active viral replication but caused a sustained inhibition of ace2 expression, triggered type 1 cytokine responses and inhibited type 2 cytokine responses. Combined, our results establish adult and larval zebrafish as useful models to investigate pathophysiological effects of SARS-CoV-2 and perform pre-clinical drug testing and validation in an inexpensive, high throughput vertebrate model. url: https://doi.org/10.1101/2020.11.06.368191 doi: 10.1101/2020.11.06.368191 id: cord-024317-w1ep0wq8 author: Ku, Zhiqiang title: Antibody therapies for the treatment of COVID-19 date: 2020-04-30 words: 2215.0 sentences: 152.0 pages: flesch: 47.0 cache: ./cache/cord-024317-w1ep0wq8.txt txt: ./txt/cord-024317-w1ep0wq8.txt summary: Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. The spike protein of SARS-CoV-2 plays an essential role in virus entry into host cells and is a primary target of neutralizing antibodies 5, 9 (Figures 1C,D) . Two MERS-CoV neutralizing mAbs, G2 and 7D10, target the S1-NTD region and function by blocking spike protein interaction with the host receptor DPP4 47, 48 . In the monkey study, researchers found that rhesus macaques infected with SARS-CoV-2 through the intratracheal route had mild illness, and their lungs showed signs of pneumonia similar to those in humans with COVID-19 58 . abstract: An outbreak of COVID-19, the disease caused by infection of the coronavirus SARS-CoV-2, that began in December 2019 in Wuhan, China has caused more than 2,990,559 confirmed human infections and 207,446 deaths as of April 27, 2020 (Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University). Scientists are working quickly on multiple aspects of the pandemic. Genetic analyses are conducted to reveal the source and evolution of SARS-CoV-2, providing knowledge that can be used to contain it and to avoid future outbreaks. Epidemiological studies which incorporates lessons learned from outbreaks of previous related viral diseases can guide development of public health measures effective to contain the current and future outbreaks. Basic virology studies reveal viral structure and function. Pathology studies inform development of strategies to interfere with infection. COVID-19 prevention and treatment strategies are being developed in preclinical and clinical studies. Antibody-based therapy is one viable treatment option. Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. We discuss in this review the current state of discovery and development of such antibodies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197606/ doi: 10.1093/abt/tbaa007 id: cord-256146-d599uera author: Kuiken, Thijs title: Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome date: 2003-07-26 words: 5686.0 sentences: 281.0 pages: flesch: 49.0 cache: ./cache/cord-256146-d599uera.txt txt: ./txt/cord-256146-d599uera.txt summary: METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, human metapneumovirus, and other respiratory pathogens. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. . Serial dilutions of the SARS-CoV virus stock and SARS-CoV-infected Vero cells from patient 5688 were made and tested with the NP and polymerase-specific RT-PCRs. Samples from the respiratory tract (nasal swabs, pharyngeal swabs, postmortem trachea, and lung samples) were also monitored for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E), and human metapneumovirus with use of essentially the same RT-PCR methods but with specific primers. Virological examinations of nasal and pharyngeal swabs, and tracheal and lung samples from all four macaques by RT-PCR for influenza A and B virus, respiratory syncytial virus A and B, rhinovirus, coronavirus (OC43 and 229E) and human metapneumovirus were negative. abstract: BACKGROUND: The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARSCoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS. METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, human metapneumovirus, and other respiratory pathogens. We infected four cynomolgus macaques (Macaca fascicularis) with SARS-CoV in an attempt to replicate SARS and did necropsies on day 6 after infection. FINDINGS: SARS-CoV infection was diagnosed in 329 (75%) of 436 patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 41 (12%) of 335, and other respiratory pathogens were diagnosed only sporadically. SARS-CoV was, therefore, the most likely causal agent of SARS. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection. Three of four macaques developed diffuse alveolar damage, similar to that in SARS patients, and characterised by epithelial necrosis, serosanguineous exudate, formation of hyaline membranes, type 2 pneumocyte hyperplasia, and the presence of syncytia. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. INTERPRETATION: Replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfill the criteria required to prove that SARS-CoV is the primary cause of SARS. Published online July 22, 2003 http://image.thelancet.com/extras/03art6318web.pdf url: https://www.ncbi.nlm.nih.gov/pubmed/12892955/ doi: 10.1016/s0140-6736(03)13967-0 id: cord-353392-rqeultbq author: Kumar, Govindarajan Venkat title: A short review on antibody therapy for COVID-19 date: 2020-04-20 words: 1944.0 sentences: 105.0 pages: flesch: 48.0 cache: ./cache/cord-353392-rqeultbq.txt txt: ./txt/cord-353392-rqeultbq.txt summary: Abstract The beginning of the novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). The third outbreak of severe illness caused by the novel SARS-CoV-2 coronavirus (COVID-19) that emerged in the Wuhan city, China, is pandemic and spread to more than 200 countries [5, 6, 7] . Based on the previous studies and reports in treating other coronaviruses such as SARS and MERS, the early administration of convalescent plasma from patients that contains raised antibodies can possibly reduce the spreading of infection and mortality [19, 20, 21, 22] . reported that the convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with SARS-CoV-2 infections. After getting approval from the ethical committee, Shenzhen, Third People''s Hospital, they administrated convalescent plasma containing neutralizing antibodies to 5 critically ill patients with SARS-CoV-2. abstract: Abstract The beginning of the novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). By April 07, 2020, SARS-CoV-2 has affected more than 1.36 million people worldwide and caused more than 75,900 deaths. To date, the anti-malaria drug hydroxychloroquine found to be a treatment option for SARS-CoV-2. In addition to supportive treatment, such as oxygen supply in moderate cases and extracorporeal membrane oxygenation in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed the antibody therapy might be an immediate strategy for emergency prophylaxis and SARS-CoV-2 therapy. url: https://doi.org/10.1016/j.nmni.2020.100682 doi: 10.1016/j.nmni.2020.100682 id: cord-275565-xerr4vki author: Kumar, Manish title: Decay of SARS-CoV-2 RNA along the wastewater treatment outfitted with Upflow Anaerobic Sludge Blanket (UASB) system evaluated through two sample concentration techniques date: 2020-09-15 words: 3456.0 sentences: 230.0 pages: flesch: 58.0 cache: ./cache/cord-275565-xerr4vki.txt txt: ./txt/cord-275565-xerr4vki.txt summary: For the first time, we present, i) an account of decay in the genetic material loading of SARS-CoV-2 during Upflow Anaerobic Sludge Blanket (UASB) treatment of wastewater, and ii) comparative evaluation of polyethylene glycol (PEG), and filtration as virus concentration methods from wastewater for the quantification of SARS-CoV-2 genes. Thus, there still remains questions pertaining to: i) capability of conventional WWTPs to reduce the abundance of SARS-CoV-2 RNA, ii) better understanding of the protocol, virus J o u r n a l P r e -p r o o f Journal Pre-proof precipitation through PEG and filtration which one is better methods for concentrating the samples before RNA isolation. Appraising the genetic loading reduction through Upflow Anaerobic Sludge Blanket (UASB) systems, and iii) Comparing the performances between PEG and filtration as virus concentration methods in terms of SARS-CoV-2 RNA sensitivity and inhibition removal. abstract: For the first time, we present, i) an account of decay in the genetic material loading of SARS-CoV-2 during Upflow Anaerobic Sludge Blanket (UASB) treatment of wastewater, and ii) comparative evaluation of polyethylene glycol (PEG), and filtration as virus concentration methods from wastewater for the quantification of SARS-CoV-2 genes. The objectives were achieved through tracking of SARS-CoV-2 genetic loadings i.e. ORF1ab, N and S protein genes on 8th and 27th May 2020 along the wastewater treatment plant (106 million liters per day) equipped with UASB system in Ahmedabad, India. PEG method performed better in removing materials inhibiting RT-qPCR for SARS-CoV-2 gene detection from the samples, as evident from constant and lower CT values of control (MS2). Using the PEG method, we found a reduction >1.3 log10 in SARS-CoV-2 RNA abundance during UASB treatment, and the RNA was not detected at all in the final effluent. The study implies that i) conventional wastewater treatment systems is effective in SARS-CoV-2 RNA removal, and ii) UASB system significantly reduces SARS-CoV-2 genetic loadings. Finally, PEG method is recommended for better sensitivity and inhibition removal during SARS-CoV-2 RNA quantification in wastewater. url: https://api.elsevier.com/content/article/pii/S0048969720358587 doi: 10.1016/j.scitotenv.2020.142329 id: cord-296986-8fuj072z author: Kumar, Manish title: A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment date: 2020-05-15 words: 4465.0 sentences: 308.0 pages: flesch: 52.0 cache: ./cache/cord-296986-8fuj072z.txt txt: ./txt/cord-296986-8fuj072z.txt summary: The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): increased transmission beyond China-fourth update abstract: Abstract In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope. url: https://www.sciencedirect.com/science/article/pii/S0048969720327959?v=s5 doi: 10.1016/j.scitotenv.2020.139278 id: cord-320935-3n157yl4 author: Kumar, Manish title: Making Waves Perspectives of Modelling and Monitoring of SARS-CoV-2 in Aquatic Environment for COVID-19 Pandemic date: 2020-09-12 words: 6613.0 sentences: 346.0 pages: flesch: 44.0 cache: ./cache/cord-320935-3n157yl4.txt txt: ./txt/cord-320935-3n157yl4.txt summary: This paper aims to collate information on recent developments on WBE in monitoring the trend of community-scale SARS-CoV-2 prevalence as well as models to predict virus spread and transmission among populations. While several studies have identified the presence of SARS-CoV-2 in the faecal matter of corona-infected patients [35, 36] , there is a growing concern on the transmission of the virus through water treatment plants (WTPs) and WWTPs. Several studies also detected the genetic material of the virus in raw wastewater across the globe [22, 26, 27] . These studies provided enough excellent reasons for modelling the spread of 2019-nCoV with the external environmental conditions, assuming that the cases of infection will decrease through secondary infection routes due to the inactivation of the virus on different surfaces; however, the possibility of transmission via direct contact remains unchanged. abstract: Prevalence of SARS-CoV-2 in the aquatic environment pertaining to the COVID-19 pandemic has been a global concern. Though SARS-CoV-2 is known as a respiratory virus, its detection in faecal matter and wastewater demonstrates its enteric involvement resulting in vulnerable aquatic environment. Here, we provide the latest updates on wastewater-based epidemiology, which is gaining interest in the current situation as a unique tool of surveillance and monitoring of the disease. Transport pathways with its migration through wastewater to surface and subsurface waters, probability of infectivity and ways of inactivation of SARS-CoV-2 are discussed in detail. Epidemiological models, especially compartmental projections, have been explained with an emphasis on its limitation and the assumptions on which the future predictions of disease propagation are based. Besides, this review covers various predictive models to track and project disease spread in the future and gives an insight into the probability of a future outbreak of the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32953402/ doi: 10.1007/s40726-020-00161-5 id: cord-252389-xrdbmosj author: Kumar, Mukesh title: Neurological manifestations and comorbidity associated with COVID-19: an overview date: 2020-10-14 words: 5447.0 sentences: 265.0 pages: flesch: 41.0 cache: ./cache/cord-252389-xrdbmosj.txt txt: ./txt/cord-252389-xrdbmosj.txt summary: In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, exploring the neurologic manifestations associated with COVID-19 is urgently required for better understanding the SARS-CoV-2 brain infections, inhibiting the additional spread and treating patients affected by this pandemic. The neuronal cells infected with virus, immune systems (microphase, T cells, and monocytes) triggered, and inflammatory system activated leads to cytokine storm, oxidative stress, and associated neurological manifestations neuroinvasiveness of SARS-CoV-2 [11, 35] . In a recent review [51] , authors have categorized the reported neurological findings related to COVID-19 into three categories: a) Central (headache, dizziness, impaired consciousness, acute cerebrovascular disease, ataxia, seizures, and special senses) b) Peripheral (hypogeusia, hyposmia) c) Musculoskeletal (ischemic or hemorrhagic) Apart from the above, increasing evidence indicated that coronaviruses may invade the CNS, causing neurological disorders. abstract: First in 2002, severe acute respiratory syndrome coronavirus (SARS-CoV), second in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), and now the third in the December 2019, emergence of tremendously pathogenic and large-scale epidemic novel coronavirus (SARS-CoV-2) has brought the worst conditions into the human inhabitants of the twenty-first century. The SARS-CoV-2 uses the resembling receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly feasts through the respiratory tract. The ACE2 receptor appearances have been also detected upon glial cells and neurons, which makes them a potential target of SARS-CoV-2 disease (COVID-19). Consequently, cells expressing ACE2, apart from lung and cardiovascular tissue, neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 systemic infection as well as its central nervous system (CNS) comorbidities. Investigation of the neurological manifestations of COVID-19 is a step towards better understanding the SARS-CoV-2 infections, inhibiting the additional spread and treating patients affected by this pandemic. In this concern, more clinical examinations for CNS involvement of SARS-CoV-2 are warranted. In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, in the perspective of COVID-19 pandemic, clinicians and healthcare workers should be aware of a wide spectrum of neurological manifestations associated with COVID-19 along with their signs and symptoms for initial diagnosis and isolation of the patients. url: https://doi.org/10.1007/s10072-020-04823-6 doi: 10.1007/s10072-020-04823-6 id: cord-311214-eqwxkwqa author: Kumar, Roshan title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 words: 2724.0 sentences: 184.0 pages: flesch: 60.0 cache: ./cache/cord-311214-eqwxkwqa.txt txt: ./txt/cord-311214-eqwxkwqa.txt summary: Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. A manually annotated reference database was generated using the Genbank 128 file of Severe acute respiratory syndrome coronavirus 2 isolate-SARS-CoV-129 2/SH01/human/2020/CHN (Accession number: MT121215) and open reading frames (ORFs) 130 were predicted against the formatted database using prokka (-gcode 1) [22] . All these isolates 189 were found to harbor 9 open reading frames coding for ORF1a (13218 bp) and ORF1b (7788 190 bp) polyproteins, surface glycoprotein or S-protein (3822 bp), ORF3a protein (828 bp Our analysis revealed that strains of human infecting SARS-CoV-2 are novel and highly 201 identical (>99.9%). In this study, the analysis was 358 performed on the genomes of the novel SARS-CoV-2 isolates recently reported from different 359 countries to understand viral pathogenesis. abstract: The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies. url: https://doi.org/10.1101/2020.03.25.006213 doi: 10.1101/2020.03.25.006213 id: cord-277841-7sp8ftbc author: Kumari, Pratibha title: Potential diagnostics and therapeutic approaches in COVID-19 date: 2020-08-12 words: 4873.0 sentences: 279.0 pages: flesch: 45.0 cache: ./cache/cord-277841-7sp8ftbc.txt txt: ./txt/cord-277841-7sp8ftbc.txt summary: Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. COVID-19 is a contagious disease, caused by a novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2). In this article, we evaluated literature for reports informing various diagnostic methods, potential antiviral chemical therapeutics, and effective treatment strategies towards clinical management of COVID-19 patients. Molecular diagnostic methods target to detect either specific regions of the viral genome or RNA-dependent RNA polymerase (RdRP) and/or structural proteins of SARS-CoV-2 (Table 1) . Like most immunological diagnostic protocols, Enzyme-Linked Immunosorbent Assay (ELISA) for COVID-19 detection uses IgM and IgG antibody against nucleocapsid (N) and receptor binding domain spike proteins (S) of SARS-CoV-2. Table 2: Primers and probes for targeting SARS-Cov-2 genes in an RT-PCR test for COVID-19 diagnosis. abstract: Abstract The most important aspect of controlling COVID-19 is its timely diagnosis. Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. This review highlights the underlying mechanisms, advancements, and clinical limitations for each of the diagnostic techniques authorized by the Food and Drug Administration (USA). Significance of diagnosis triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted to make medical and research community more informed so that better clinical strategies are developed. We have discussed here the clinical manifestations and hospital outcomes along with the underlying mechanisms for several drugs administered to COVID-19 prophylaxis. In addition to favourable clinical outcomes, the challenges, and the future directions of management of COVOD-19 are highlighted. Having a comprehensive knowledge of the diagnostic approaches of SARS-CoV-2, and its pathogenesis will be of great value in designing a long-term strategy to tackle COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0009898120303958?v=s5 doi: 10.1016/j.cca.2020.08.013 id: cord-293578-yu2i0u2h author: Kusadasi, Nuray title: A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy date: 2020-08-10 words: 3914.0 sentences: 259.0 pages: flesch: 38.0 cache: ./cache/cord-293578-yu2i0u2h.txt txt: ./txt/cord-293578-yu2i0u2h.txt summary: The potential role of plasma kallikrein in case of SARS-CoV-2 infection may be summarized as (1) the activation of FXII with the end-product thrombin (coagulation system) (2) the generation of bradykinin with subsequent vascular permeability and leakage (kallikrein-kinin system), (3) the activation of the renin-angiotensin system through conversion of renin from pre-renin leading to a pro-inflammatory state through increased angiotensin 1 receptor activation and (4) the activation of C5, in part through activation of C1 via FXII and in part through activation of C3 via plasmin (complement system). 54, 55 Since prekallikrein is seen as a potential regulator in the fibrin clot formation through FXII activation and is involved in the pathogenesis of thrombosis, there might be an important role for controlling the hypercoagulable state of the patients infected with SARS-CoV-2 as a therapeutic target. Taken together, all these mechanisms may contribute to the complex hypercoagulable state of the critically ill patients infected with SARS-CoV-2 having severe hypoxia and ongoing endothelial activation. abstract: Recent evidence is focusing on the presence of a hypercoagulable state with development of both venous and arterial thromboembolic complications in patients infected with SARS-CoV-2. The ongoing activation of coagulation related to the severity of the illness is further characterized by thrombotic microangiopathy and endotheliitis. These microangiopathic changes cannot be classified as classical disseminated intravascular coagulation (DIC). In this short review we describe the interaction between coagulation and inflammation with focus on the possible mechanisms that might be involved in SARS-CoV-2 infection associated coagulopathy in the critically ill. url: https://doi.org/10.1097/hs9.0000000000000457 doi: 10.1097/hs9.0000000000000457 id: cord-104500-m0kfom0x author: Kyriakopoulos, Anthony M. title: The Potential Role of Super Spread Events in SARS-COV-2 Pandemic; a Narrative Review date: 2020-09-21 words: 6842.0 sentences: 357.0 pages: flesch: 40.0 cache: ./cache/cord-104500-m0kfom0x.txt txt: ./txt/cord-104500-m0kfom0x.txt summary: A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic" and were published before 20(th) of August 2020. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. Following this initial selection stage, further screening was performed by all reviewers, using the previously described search items to identify parameters determining the global impact of COVID-19 due to SSEs. Identified parameters included the global impact of immunity and vaccination, the holy cup and religion transmission, and the austerity caused by COVID-19 and other coronavirus epidemics due to restrictions applied. abstract: Coronaviruses, members of Coronaviridae family, cause extensive epidemics of vast diseases like severe acute respiratory syndrome (SARS) and Coronavirus Disease-19 (COVID-19) in animals and humans. Super spread events (SSEs) potentiate early outbreak of the disease and its constant spread in later stages. Viral recombination events within species and across hosts lead to natural selection based on advanced infectivity and resistance. In this review, the importance of containment of SSEs was investigated with emphasis on stopping COVID-19 spread and its socio-economic consequences. A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the “potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic” and were published before 20(th) of August 2020. Overall, ninety-eight articles were found eligible and reviewed. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. The effect of SSEs on previous SARS epidemics has been documented in detail. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. This is crucial for SARS-COV-2 pandemic containment as the vaccine(s) development process will take considerable time to safely establish its potential usefulness for future clinical usage. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587986/ doi: nan id: cord-332080-923jpec0 author: Lai, Chih-Cheng title: In vitro diagnostics of coronavirus disease 2019: technologies and application date: 2020-06-05 words: 1189.0 sentences: 92.0 pages: flesch: 58.0 cache: ./cache/cord-332080-923jpec0.txt txt: ./txt/cord-332080-923jpec0.txt summary: Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. (Hangzhou Bigfish Bio-tech Co., Ltd., Zhejiang, China) was recently registered 127 as a CE-IVD for detecting SARS-CoV-2 ORF-1ab and N genes in 128 nasopharyngeal swabs, sputum, and BAL fluids. The 145 performance of the Xpress SARS-CoV-2 test was clinically evaluated in 146 patients with respiratory illnesses from whom contrived nasopharyngeal swab 147 samples were collected into viral transport media. Serological tests that can detect SARS-CoV-2 IgG-IgM antibodies are simpler 248 than rRT-PCR, and do not require complicated equipment and protocols 249 (Table 3) . During the previous SARS 251 epidemic, the IgM antibody was the first line of defense during viral infections 252 and was detectable in blood samples from patients after 3 -6 days. Dynamics of 617 anti-SARS-Cov-2 IgM and IgG antibodies among COVID-19 patients abstract: Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19. url: https://api.elsevier.com/content/article/pii/S1684118220301407 doi: 10.1016/j.jmii.2020.05.016 id: cord-267782-4pjfnund author: Lan, Fan-Yun title: Association between SARS-CoV-2 infection, exposure risk and mental health among a cohort of essential retail workers in the USA date: 2020-10-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVES: To investigate SARS-CoV-2 (the virus causing COVID-19) infection and exposure risks among grocery retail workers, and to investigate their mental health state during the pandemic. METHODS: This cross-sectional study was conducted in May 2020 in a single grocery retail store in Massachusetts, USA. We assessed workers’ personal/occupational history and perception of COVID-19 by questionnaire. The health outcomes were measured by nasopharyngeal SARS-CoV-2 reverse transcriptase PCR (RT-PCR) results, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULTS: Among 104 workers tested, 21 (20%) had positive viral assays. Seventy-six per cent positive cases were asymptomatic. Employees with direct customer exposure had an odds of 5.1 (95% CI 1.1 to 24.8) being tested positive for SARS-CoV-2 after adjustments. As to mental health, the prevalence of anxiety and depression (ie, GAD-7 score >4 or PHQ-9 score >4) was 24% and 8%, respectively. After adjusting for potential confounders, those able to practice social distancing consistently at work had odds of 0.3 (95% CI 0.1 to 0.9) and 0.2 (95% CI 0.03 to 0.99) screening positive for anxiety and depression, respectively. Workers commuting by foot, bike or private cars were less likely to screen positive for depression (OR 0.1, 95% CI 0.02 to 0.7). CONCLUSIONS: In this single store sample, we found a considerable asymptomatic SARS-CoV-2 infection rate among grocery workers. Employees with direct customer exposure were five times more likely to test positive for SARS-CoV-2. Those able to practice social distancing consistently at work had significantly lower risk of anxiety or depression. url: https://www.ncbi.nlm.nih.gov/pubmed/33127659/ doi: 10.1136/oemed-2020-106774 id: cord-326017-qw4qynqv author: Laskar, Partha title: “Tomorrow Never Dies”: Recent Advances in Diagnosis, Treatment, and Prevention Modalities against Coronavirus (COVID-19) amid Controversies date: 2020-08-06 words: 14797.0 sentences: 760.0 pages: flesch: 42.0 cache: ./cache/cord-326017-qw4qynqv.txt txt: ./txt/cord-326017-qw4qynqv.txt summary: Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Considering this, we have summarized diverse research areas covering the current known biological properties of SARS-CoV-2, diagnostic tools for detection, therapeutic measurements for possible treatment, and prevention techniques to stop further spreading of this pandemic. Overall, real-time RT-PCR based method enables developing a high-throughput testing for rapid, on-demand, low-cost, reliable, quantitative detection technique against COVID-19 in clinical settings [39] . Another newly developed method, SARS-CoV-2 DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR), was found to perform simultaneous reverse transcription and isothermal amplification by (i) RT-LAMP for RNA extracted (for nasopharyngeal or oropharyngeal swabs), (ii) Cas12 detection of predefined coronavirus sequences, and (iii) cleavage of a reporter molecule confirms, which detects the virus [56] . abstract: The outbreak of novel coronavirus disease (2019-nCoV or COVID-19) is responsible for severe health emergency throughout the world. The attack of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found to be responsible for COVID-19. The World Health Organization has declared the ongoing global public health emergency as a pandemic. The whole world fights against this invincible enemy in various capacities to restore economy, lifestyle, and safe life. Enormous amount of scientific research work(s), administrative strategies, and economic measurements are in place to create a successful step against COVID-19. Furthermore, differences in opinion, facts, and implementation methods laid additional layers of complexities in this battle against survival. Thus, a timely overview of the recent, important, and overall inclusive developments against this pandemic is a pressing need for better understanding and dealing with COVID-19. In this review, we have systematically summarized the epidemiological studies, clinical features, biological properties, diagnostic methods, treatment modalities, and preventive measurements related to COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32781617/ doi: 10.3390/diseases8030030 id: cord-270533-s2d3q4ob author: Lau, Yu-Lung title: SARS: future research and vaccine date: 2004-11-05 words: 3000.0 sentences: 167.0 pages: flesch: 47.0 cache: ./cache/cord-270533-s2d3q4ob.txt txt: ./txt/cord-270533-s2d3q4ob.txt summary: Severe acute respiratory syndrome (SARS), a newly emerged infectious disease of humans in the 21st century, appeared in Guangdong Province in Southern China in November 2002 and spread to 26 countries on five continents along international air travel routes, causing large scale outbreaks in Hong Kong, Singapore and Toronto in early 2003. This novel CoV has satisfied Koch''s postulates for causation by its consistent isolation from SARS patients, viral isolation, reproduction of disease in non-human primates after inoculation and the presence of specific antibody response against the virus in both patients and experimentally infected primates 8 . Indeed, sporadic reemergence of cases have been reported in Guangdong Province as well as from research laboratories Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. abstract: Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. A novel coronavirus (CoV) was identified as its aetiological agent and its genome was sequenced within months of the World Health Organisation issuing a global threat on SARS. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. This will depend on understanding the pathogenesis and immune response to SARS CoV. Further understanding of the ecology of SARS CoV in human and animals will help prevent future cross species transmission. Likewise for the super-spreading events, clarification of the underlying reasons will be important to prevent a large scale outbreak of SARS. Lastly it is of utmost importance that international research collaboration should be strengthened to deal with SARS and any other emerging infectious disease that can seriously threaten our future. url: https://www.ncbi.nlm.nih.gov/pubmed/15531254/ doi: 10.1016/j.prrv.2004.07.005 id: cord-296602-19noki6p author: Law, Helen KW title: Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells date: 2009-06-08 words: 4427.0 sentences: 230.0 pages: flesch: 53.0 cache: ./cache/cord-296602-19noki6p.txt txt: ./txt/cord-296602-19noki6p.txt summary: In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. Interestingly, the SARS-CoV infected DCs showed low expression of antiviral cytokines (IFN-α, IFN-β, IFN-γ and IL-12p40), moderate upregulation of proinflammatory cytokines (TNF-α and IL-6) but significant upregulation of inflammatory chemokines (macrophage inflammatory protein (MIP)-1α/CCL3, regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL-5, interferon-inducible protein of 10 kD (IP-10)/CXCL10 and monocyte chemotactic protein (MCP)-1/CCL2. abstract: BACKGROUND: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. RESULTS: Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted. url: https://www.ncbi.nlm.nih.gov/pubmed/19505311/ doi: 10.1186/1471-2172-10-35 id: cord-304418-k9owyolj author: Le Maréchal, M. title: COVID-19 in clinical practice: a narrative synthesis date: 2020-09-29 words: 6288.0 sentences: 367.0 pages: flesch: 49.0 cache: ./cache/cord-304418-k9owyolj.txt txt: ./txt/cord-304418-k9owyolj.txt summary: Plasmatic detection of SARS-CoV-2 has been reported but only with low viral titers, and mainly in clinically severe cases [44] ; bloodstream infectivity has yet to be demonstrated. The first large clinical trial published on LPV/RTV on SARS-CoV-2 compared 99 patients receiving the antiviral vs 100 receiving SoC alone [124] ; there was no difference between the 2 groups regarding the primary end point (time to improvement) (15 vs 16 days, p=0.09). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China Severity or Risk of Death in Patients with Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China abstract: The coronavirus disease 2019 (COVID-19) was first reported in the city of Wuhan, China. The disease rapidly spread to the rest of China, to Southern-East Asia, then to Europe, America, and on to the rest of the world. COVID-19 is associated with a betacoronavirus named SARS-CoV-2. The virus penetrates the organism through the respiratory tract, conveyed by contaminated droplets. The main cell receptor targeted is the surface-bound ACE-2. As of the 26th July 2020, 15,200,000 COVID-19 cases and 650,000 deaths were reported worldwide. The mortality rate is estimated between 1.3 and 18.3%. The reproductive rate without any public health intervention is estimated around 4-5.1 in France. Most hospitalized patients for COVID-19 present respiratory symptoms, which in some cases is associated with fever. Up to 86% of admissions to ICU are related to acute respiratory failure. To date, no anti-viral therapy has proven its efficacy considering randomized trials. Only immunomodulatory treatments such as corticosteroids have shown to cause significant improvement in patient outcome. url: https://www.ncbi.nlm.nih.gov/pubmed/33007400/ doi: 10.1016/j.medmal.2020.09.012 id: cord-324557-4u8dja0n author: Leblanc, Jean‐François title: Risk of Transmission of Severe Acute Respiratory Syndrome Coronavirus‐2 by Transfusion: A Literature Review date: 2020-08-15 words: 3044.0 sentences: 195.0 pages: flesch: 50.0 cache: ./cache/cord-324557-4u8dja0n.txt txt: ./txt/cord-324557-4u8dja0n.txt summary: Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biological sample and infectivity requires a minimal RNA load, which is rarely, if at all observed, in blood components. More specifically, PubMed was interrogated with a series of queries aimed at identifying references that relate to COVID-19/SARS-CoV-2 and the detection of viral genomic material in blood, plasma, or serum. From this screen, 23 references reporting any data or stating any information on the detection of SARS-CoV-2 genomic material in human blood, plasma, or serum, were selected ( Table 2) . An exhaustive search strategy led to the identification of 23 references reporting data on the detection of SARS-CoV-2 genomic material in blood components (Table 2) . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel human coronavirus responsible for coronavirus disease 2019 (COVID‐19). The emergence of this virus in Wuhan (China) at the end of 2019, and its worldwide spread to reach the pandemic stage, has raised concerns about the possible risk that it might be transmissible by transfusion. This theoretical risk is further supported by reports of the detection of viral RNA in the blood of some infected individuals. To further address this risk, a thorough PubMed literature search was performed to systematically identify studies reporting data on the detection of SARS‐CoV‐2 RNA in blood or its components. Complementary searches were done to identify articles reporting data on the in vitro infectivity of blood components. At least 23 articles presenting data on the detection of SARS‐CoV‐2 RNA in blood, plasma, or serum were identified. Of these, three studies reported on blood donors with COVID‐19 infection identified post‐donation, and no cases of transfusion transmission were identified. A few studies mentioned results of in vitro infectivity assays of blood components in permissive cell lines, none of which were able to detect infectious virus in blood or its components. Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biological sample and infectivity requires a minimal RNA load, which is rarely, if at all observed, in blood components. Overall, the available evidence suggests that the risk of transmission of SARS‐CoV‐2 by transfusion remains theoretical. url: https://doi.org/10.1111/trf.16056 doi: 10.1111/trf.16056 id: cord-279105-e2zjxjox author: Lee, Cheryl Yi-Pin title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 words: 3872.0 sentences: 212.0 pages: flesch: 44.0 cache: ./cache/cord-279105-e2zjxjox.txt txt: ./txt/cord-279105-e2zjxjox.txt summary: With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection. abstract: Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control. url: https://www.ncbi.nlm.nih.gov/pubmed/32391022/ doi: 10.3389/fimmu.2020.00879 id: cord-265366-vmuqbpkk author: Leibowitz, Jill title: Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without SARS-CoV-2 Infection date: 2020-10-09 words: 2626.0 sentences: 142.0 pages: flesch: 54.0 cache: ./cache/cord-265366-vmuqbpkk.txt txt: ./txt/cord-265366-vmuqbpkk.txt summary: 7, 8, 9, 10, 11, 12, 13 The largest case series to date describes 18 infants younger than 90 days of age who tested positive for SARS-CoV-2, 14 of whom were febrile. 9 The objective of this study was to compare the clinical and demographic characteristics and hospital course of febrile infants who presented to Cohen Children''s Medical Center (CCMC) during March and April of 2020, the time period of peak COVID-19 incidence in our region, to febrile infants treated in CCMC during March and April of previous years. The key findings of our study are that during the peak of the COVID-19 pandemic in New York, SARS-CoV-2 was the predominant pathogen identified among febrile infants younger than 57 days of age, and the disease was self-limited in all infants with COVID-19. 26 Infants with COVID-19 presented with lethargy and feeding difficulty more with SARS-CoV-2 infection among infants younger than 90 days of age. abstract: OBJECTIVE: To determine features that distinguish febrile young infants with SARS-CoV-2 infection. STUDY DESIGN: Retrospective single-center study included febrile infants <57 days evaluated in the Emergency Department of Cohen Children’s Medical Center of Northwell Health, New Hyde Park, New York during March 1-April 30 of 2018, 2019, and 2020. Sociodemographic and clinical features were compared between those seen during the 2020 COVID-19 pandemic and previous years, as well as between SARS-CoV-2 infected infants and SARS-CoV-2 uninfected infants (SARS-CoV-2 negative or evaluated during 2018 and 2019). RESULTS: In all, 124 febrile infants <57 days of age were identified; 38 during the 2-month study period in 2018, 33 in 2019, and 53 in 2020. During 2020, fewer febrile infants had a serious bacterial infection (SBI) or a positive respiratory viral panel (RVP) than in prior years (6% versus 21%, P = .02; 15% versus 53%, p<.001, respectively). SARS-CoV-2 was the most frequent pathogen detected in 2020; of 30 infants tested, 20 tested positive. Infants with SARS-CoV-2 were more likely to identify as Hispanic (p=.004), have public insurance or were uninsured (p=.01), exhibited lethargy (p=.02), had feeding difficulties (p=.002), and had lower white blood cell (p=.001), neutrophil (p<.001), and lymphocyte counts (p=.005) than the 81 infants without SARS-CoV-2 infection. None of the infants with SARS-CoV-2 had concurrent SBI or detection of another virus. Overall, disease in infants with SARS-CoV-2 was mild. CONCLUSIONS: During the peak of the pandemic, SARS-CoV-2 was the predominant pathogen among febrile infants. Socioeconomic, historical, and laboratory features differed significantly between SARS-CoV-2 infected and uninfected infants. None of the 20 infants with SARS-CoV-2 infection had an identified co-viral or serious bacterial infection. url: https://www.sciencedirect.com/science/article/pii/S0022347620312646?v=s5 doi: 10.1016/j.jpeds.2020.10.002 id: cord-346777-zmmnn9b2 author: Lester, Sandra title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies date: 2019-09-11 words: 5372.0 sentences: 256.0 pages: flesch: 44.0 cache: ./cache/cord-346777-zmmnn9b2.txt txt: ./txt/cord-346777-zmmnn9b2.txt summary: title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. These results demonstrate that the MERS-CoV-S protein pseudotyped VSV particle-based neutralization assay would serve as a safe, reliable and highly specific alternative method to detect MERS-CoV neutralizing antibodies to be used for future sero-epidemiological studies. A laboratory-confirmed SARS-CoV patient serum sample and a panel of human sera with confirmed high neutralizing antibody titres to human coronaviruses 229E, HKU1, OC43 and NL63 were used in this study to evaluate the VSV-MERS-CoV-S particle-based neutralization assay for potential cross-neutralization. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic coronavirus that was identified in 2012. MERS-CoV infection in humans can result in an acute, severe respiratory disease and in some cases multi-organ failure; the global mortality rate is approximately 35 %. The MERS-CoV spike (S) protein is a major target for neutralizing antibodies in infected patients. The MERS-CoV microneutralization test (MNt) is the gold standard method for demonstrating prior infection. However, this method requires the use of live MERS-CoV in biosafety level 3 (BSL-3) containment. The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. Using a panel of human sera from confirmed MERS-CoV patients, the VSV-MERS-CoV particle neutralization assay produced results that were highly comparable to those of the microneutralization test using live MERS-CoV. The results suggest that the VSV-MERS-CoV-S pseudotype neutralization assay offers a highly specific, sensitive and safer alternative method to detect MERS-CoV neutralizing antibodies in human sera. url: https://doi.org/10.1099/acmi.0.000057 doi: 10.1099/acmi.0.000057 id: cord-338205-sy91rnse author: Li, Chenxi title: Laboratory Diagnosis of Coronavirus Disease-2019 (COVID-19) date: 2020-07-02 words: 7515.0 sentences: 436.0 pages: flesch: 51.0 cache: ./cache/cord-338205-sy91rnse.txt txt: ./txt/cord-338205-sy91rnse.txt summary: With limited understanding of COVID-19, it is difficult to exclude SARS-CoV-2 infection based on a single negative PCR result, especially when testing was used for upper respiratory tract specimens. The study found that SARS-CoV-2 could be detected in all primer-probe sets applied in the qRT-PCR tests, but significant discrepancy was observed in the detection limit and the ability to identify negatives and positives with a lower viral load. Compared with the qRT-PCR kit, nested RT-PCR analysis showed higher sensitivity and specificity, indicating that it is more suitable for clinical application to detect SARS-CoV-2 in cases with low viral load. In cases where RT-PCR assays are negative and there is a strong epidemiological link to SARS-CoV-2 infection, paired serum samples (in the acute and convalescent-phase) could support diagnosis once validated serology tests are available with the initial samples collected in the first week of COVID-19 and the second collected after 2-4 weeks [28] . abstract: Abstract The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Point-of-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32621814/ doi: 10.1016/j.cca.2020.06.045 id: cord-341254-xnj6slby author: Li, Hua title: A new and rapid approach for detecting COVID‐19 based on S1 protein fragments date: 2020-06-05 words: 1945.0 sentences: 120.0 pages: flesch: 46.0 cache: ./cache/cord-341254-xnj6slby.txt txt: ./txt/cord-341254-xnj6slby.txt summary: Based on it, the detection of IgM/IgG in blood became an optional approach to improve the diagnosis, especially for the COVID-19 patient with negative nucleic acid test result. 2. Colloidal gold-labeled mouse-antihuman lgM/lgG antibody was manufactured by SAIYA Hebei Biotechnology Co., Ltd. To obtain the well-performance antibody, the antibody was selected for functional test including the positive and negative coincidence rates, minimum test threshold, and accelerated stability. Due to only around 50% positive rate of SARS-CoV-2 nucleic acid test 8, 12 under various condition of sample collection and storage, viral infection regions, RNA extraction methods, the quality of nucleic acid detection kit, and so on, 13 detection of IgM/IgG became a powerful approach for the early diagnosis of COVID-19 and could help identify the patients with negative nucleic acid but with obvious clinical symptoms. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis abstract: The pandemic of novel coronavirus disease 2019 (COVID‐19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor‐binding domain of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS‐CoV‐2 rapid test kit: the colloidal gold‐labeled mouse‐antihuman lgM/lgG antibody, the recombinant SARS‐CoV‐2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription‐polymerase chain reaction (RT‐PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS‐CoV‐2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID‐19. url: https://www.ncbi.nlm.nih.gov/pubmed/32508026/ doi: 10.1002/ctm2.90 id: cord-298067-awo3smgp author: Li, Huanjie title: Transmission Routes Analysis of SARS-CoV-2: A Systematic Review and Case Report date: 2020-07-10 words: 4853.0 sentences: 268.0 pages: flesch: 51.0 cache: ./cache/cord-298067-awo3smgp.txt txt: ./txt/cord-298067-awo3smgp.txt summary: Through associating infection symptoms with the transmission routes of virus and the patient course of the disease, we expect to provide guidelines for clinical diagnosis and the basis for suppressing the spread of the virus and antiviral treatment. On February 1, 2020, respiratory samples of four patients were confirmed SARS-CoV-2 infections by real-time PCR in Jinan Central Hospital, Shandong province, China. Summarizing the published articles, including SARS-CoV and SARS-CoV-2, we combined with epidemiological and clinical data to analyze the possible routes of asymptomatic patients with virus infection in order to provide the basis for suppressing the spread of the virus, and antiviral treatment and advice for the protection of medical staff. The study found that the detection of SARS-CoV-2 nucleic acid positive in a few feces of patients with confirmed COVID-19 cases indicated the presence of a live virus. abstract: The global outbreak of SARS-CoV-2 spread rapidly throughout the world which transmitted among humans through various routes. Asymptomatic (carriers) and possible fecal-oral transmission, resulted into a large-scale spread. These issues pose great challenges to disease diagnosis and epidemic control. We obtained data on 29 cases of COVID-19 patients in Jinan, China, and reported the clinical data of asymptomatic patients confirmed with stool samples positive. Some patients with gastrointestinal infections are secondary to pulmonary infections, and during the patients' recovery period, the virus may still existin the patient's gastrointestinal tract over 7 days. We combined with epidemiological and clinical data of asymptomatic patients to analyze the possible routes of viral transmission and infection, including eyes-nose, hands-eyes, fecal-oral, and eyes-oral, et al., thus first presented the two-way transmission through eyes-oral. Through associating infection symptoms with the transmission routes of virus and the patient course of the disease, we expect to provide guidelines for clinical diagnosis and the basis for suppressing the spread of the virus and antiviral treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/32754600/ doi: 10.3389/fcell.2020.00618 id: cord-029547-9ei1ram3 author: Li, Jingwei title: The epidemiology and therapeutic options for the COVID-19 date: 2020-05-28 words: 7841.0 sentences: 499.0 pages: flesch: 48.0 cache: ./cache/cord-029547-9ei1ram3.txt txt: ./txt/cord-029547-9ei1ram3.txt summary: According to the Diagnosis and Treatment Program of Novel Coronavirus Pneumonia, only a suspected case has one of the pieces of evidence of etiology or serology, such as positive nucleic acid, confirmation of gene sequencing, and virus specific antibody, to be confirmed to be COVID-19 patient, 55 and the suspected cases were identified by a comprehensive analysis of epidemiological history and clinical manifestations. 64 There have been tens of clinical trials to confirm the safety and efficiency of chloroquine in treating COVID-19 patients, and its mechanism can be described as interfering with the glycosylation of ACE2 or alkalizing the phagolysosome to inhibit viral replication, 65, 66 which prevents the SARS-Cov-2 entering the host cells. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial abstract: An outbreak of coronavirus disease 2019 (COVID-19), a disease caused by a novel pneumonia virus, has affected over 200 countries and regions worldwide. With the increasing number of patients and deaths, WHO have declared it as a global pandemic currently, indicating a third large-scale epidemic coronavirus has appeared since the emergence of severe acute respiratory syndrome coronavirus (SARS) and Middle-East respiratory syndrome (MERS) in the twenty-first century. Considering the great harm it has caused, researchers throughout the world have been chasing to exploit the pathophysiology, characteristics, and potential remedies for COVID-19 to better battle the outbreak. Therefore, the current study revisits advances of the virology, epidemiology, clinical features, therapeutic options, and prevention of COVID-19. The features of asymptomatic carriers are also been explored. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376264/ doi: 10.1093/pcmedi/pbaa017 id: cord-253905-zknmfgsh author: Li, Xingguang title: Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 date: 2020-03-11 words: 3846.0 sentences: 194.0 pages: flesch: 49.0 cache: ./cache/cord-253905-zknmfgsh.txt txt: ./txt/cord-253905-zknmfgsh.txt summary: To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. Homology plot analysis of "dataset_6" also revealed that BetaCoV/bat/Yunnan/ RaTG13/2013 was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378), consistent with phylogenetic analysis ( Figure S5 ). 46, 47 Bayesian analyses with the tip-dating method using a strict clock as well as constant size coalescent tree prior indicated that SARS-CoV-2 is evolving at a rate of 1.24 × 10 −3 substitutions per site per year (Table 1 ), in accordance with our prior research 46, 47 and similar to that found for other human F I G U R E 4 Estimated maximum-clade-credibility tree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using tip-dating method. abstract: To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS‐CoV‐2 virus, we reanalyzed virome data sets from pangolins and representative SARS‐related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood‐mapping, and comparative analyses of the genomes. Based on Bayesian time‐scaled phylogenetic analysis using the tip‐dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS‐CoV‐2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10(−3) substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS‐CoV‐2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS‐CoV‐2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS‐CoV‐2 virus, which is responsible for the recent outbreak of COVID‐19, did not come directly from pangolins. url: https://doi.org/10.1002/jmv.25731 doi: 10.1002/jmv.25731 id: cord-312664-tgpaidhp author: Liang, Julia title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex date: 2020-05-28 words: 3050.0 sentences: 189.0 pages: flesch: 52.0 cache: ./cache/cord-312664-tgpaidhp.txt txt: ./txt/cord-312664-tgpaidhp.txt summary: title: Interaction of the prototypical α-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. Further, molecular dynamics simulations highlight the stability of the interaction of the α-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (ΔG = -25.2 and -22.3 kcal/mol for protomers A and B). Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M pro . abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. In the absence of a vaccine, or an approved effective therapeutic, there is an intense interest in repositioning available drugs or designing small molecule antivirals. In this context, in silico modelling has proven to be an invaluable tool. An important target is the SARS-CoV-2 main protease (M(pro)), involved in processing translated viral proteins. Peptidomimetic α-ketoamides represent prototypical inhibitors of M(pro). A recent attempt at designing a compound with enhanced pharmacokinetic properties has resulted in the synthesis and evaluation of the α-ketoamide 13b analogue. Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of α-ketoamide 13b with the active site of the SARS-CoV-2 M(pro). We included the widely used antibiotic, amoxicillin, for comparison. Our findings indicate that α-ketoamide 13b binds more tightly (predicted GlideScore = -8.7 and -9.2 kcal/mol for protomers A and B, respectively), to the protease active site compared to amoxicillin (-5.0 and -4.8 kcal/mol). Further, molecular dynamics simulations highlight the stability of the interaction of the α-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (ΔG = -25.2 and -22.3 kcal/mol for protomers A and B). In contrast, amoxicillin interacts unfavourably with the protease (ΔG = +32.8 kcal/mol for protomer A), with unbinding events observed in several independent simulations. Overall, our findings are consistent with those previously observed, and highlight the need to further explore the α-ketoamides as potential antivirals for this ongoing COVID-19 pandemic. url: https://www.sciencedirect.com/science/article/pii/S1476927120304205?v=s5 doi: 10.1016/j.compbiolchem.2020.107292 id: cord-274834-24v2b509 author: Lima, Rosiane title: Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children date: 2020-09-11 words: 5588.0 sentences: 268.0 pages: flesch: 40.0 cache: ./cache/cord-274834-24v2b509.txt txt: ./txt/cord-274834-24v2b509.txt summary: Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. Specific questions that must be addressed revolve around the role children play in viral transmission, differences in pediatric viral susceptibility and immune responses, which could guide potential therapies for adults, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the development of severe hyperinflammatory shock and cardiac damage seen in Multisystem Inflammatory Syndrome in Children (MIS-C). In order to capture the full range of SARS-CoV-2 infection in the pediatric population, a COVID-19 biospecimen collection study was designed and implemented, including patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2-infected mothers, and asymptomatic children. abstract: BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies. url: https://www.ncbi.nlm.nih.gov/pubmed/32917141/ doi: 10.1186/s12874-020-01110-y id: cord-276630-qci7khki author: Lima, William Gustavo title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review date: 2020-06-08 words: 3727.0 sentences: 214.0 pages: flesch: 49.0 cache: ./cache/cord-276630-qci7khki.txt txt: ./txt/cord-276630-qci7khki.txt summary: Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. Only seven drugs (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, Table 1 Clinical evidence of potential candidates for drug repositioning against COVID-19 (SARS-CoV-2) *Lopinavir (400 mg) + ritonavir (100 mg), q12h, orally; associated with umifenovir (200 mg), q12h, orally. [14] reported that the use of arbidol in combination with lopinavir/ritonavir inhibits the aggravation of pneumonia caused by SARS-CoV-2 and promotes a virus-negative conversion in patients from China. Of these, only six drugs (lopinavir/ritonavir, umifenovir (arbidol), remdesivir, chloroquine, and hydroxychloroquine) have shown promising results in preclinical trials and have clinically lessened the symptoms of COVID-19. Although lopinavir/ ritonavir had low anti-SARS-CoV-2 activity, arbidol, remdesivir, and chloroquine/hydroxychloroquine showed promising effects against this coronavirus. abstract: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s00705-020-04693-5 doi: 10.1007/s00705-020-04693-5 id: cord-272603-nbosceoz author: Lin, Qiuyuan title: Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min date: 2020-07-02 words: 1882.0 sentences: 98.0 pages: flesch: 42.0 cache: ./cache/cord-272603-nbosceoz.txt txt: ./txt/cord-272603-nbosceoz.txt summary: Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. 26 To meet the challenge of the large epidemic, we describe the development of a point-of-care microfluidic platform integrating a homemade fluorescence detection analyzer ( Figure 1A ), SARS-CoV-2 diagnostic microchips ( Figure 1B) , and multiple immunoassays ( Figure 1C ) for detecting three biomarkers (IgG, IgM, and antigen). This robust microfluidic immunoassay system can provide a useful tool for SARS-CoV-2 diagnosis in public health laboratories as well as for timely screening potentially infected patients to monitor and prevent the epidemic owning to its capability of easy, fast, cost-effective, and point-of-care detection. abstract: [Image: see text] The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide. url: https://doi.org/10.1021/acs.analchem.0c01635 doi: 10.1021/acs.analchem.0c01635 id: cord-270116-r2rnnsfh author: Lippi, Giuseppe title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) date: 2020-05-11 words: 4742.0 sentences: 192.0 pages: flesch: 37.0 cache: ./cache/cord-270116-r2rnnsfh.txt txt: ./txt/cord-270116-r2rnnsfh.txt summary: As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Recent studies have also been published on the possibility to use rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for SARS-CoV-2 detection, but additional evidence is needed at this point in time for validating their routine usage in COVID-19 diagnostics (38, 39) . As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. abstract: Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays. (www.actabiomedica.it) url: https://www.ncbi.nlm.nih.gov/pubmed/32420937/ doi: 10.23750/abm.v91i2.9548 id: cord-334773-yw2qgv13 author: Lisco, Giuseppe title: Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review date: 2020-08-10 words: 7901.0 sentences: 359.0 pages: flesch: 32.0 cache: ./cache/cord-334773-yw2qgv13.txt txt: ./txt/cord-334773-yw2qgv13.txt summary: This concern has been further confirmed by the results of a cohort study among 85 fatal cases of COVID-19 in Wuhan, hence defining DM as a potentially harmful comorbidity predisposing to worse clinical course or death once SARS-CoV-2 infection occurred [49] . Different hypothesis should be considered for explaining this clinical phenomenon, including glucose control at baseline and during the infection course, pathophysiology and immune system response in SARS-CoV-2 infected patients with T2D, diabetes-related comorbidities and concomitant medications. In conclusion, diabetic patients especially elderly individuals and those with worse baseline glucose control may exhibit immune system dysregulation that predispose them to a less effective response against SARS-CoV-2 and to a dysfunctional inflammation that requires to be carefully monitored in confirmed cases of COVID-19, for preventing or avoiding a harmful progression of the disease. Immune response and systemic inflammation play a crucial role in SARS-CoV-2 infection, particularly in case of severe clinical course of the disease. abstract: PURPOSE: Epidemiological data suggest that comorbid patients, mostly those with type 2 diabetes (T2D), are predisposed to poor prognosis in Coronavirus disease 2019 (COVID-19), leading to serious healthcare concerns. The aim of the present manuscript is to review the main relevant mechanisms possibly contributing to worsen the clinical course of COVID-19 in T2D. RESULTS: Poor glucose control, high glycaemic variability and diabetes-related comorbidities at baseline, particularly cardiovascular diseases and obesity, contribute in worsening the prognosis in the above-mentioned cluster of patients. Moreover, both a lower efficient innate immune system response and cytokine dysregulation predispose patients with T2D to impaired viral clearance and more serious pulmonary and systemic inflammation once the SARS-CoV-2 infection occurred. Inconclusive data are currently available for specifically indicate or contraindicate concurrent medications for managing T2D and its comorbidities in infected patients. CONCLUSIONS: T2D individuals should be considered as more vulnerable to COVID-19 than general population, and thus require adequate advices about hygienic tips to protect themselves during the pandemic. A careful management of glucose levels and diabetes-related comorbidities remains essential for avoiding further complications, and patient monitoring during the pandemic should be performed also at distance by means of telemedicine. Further studies are needed to clarify whether medications normally used for managing T2D and its associated comorbidities could have a protective or detrimental effect on COVID-19 clinical course. url: https://doi.org/10.1007/s12020-020-02444-9 doi: 10.1007/s12020-020-02444-9 id: cord-345371-pjbviagq author: Lisi, Lucia title: Approaching Coronavirus Disease 2019: mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2 date: 2020-07-23 words: 10648.0 sentences: 512.0 pages: flesch: 37.0 cache: ./cache/cord-345371-pjbviagq.txt txt: ./txt/cord-345371-pjbviagq.txt summary: The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. Here, we review the recently published literature on the pharmacological treatments used so far and/or undergoing evaluation in clinical trials, with focus on the biochemical mechanisms of action of repurposed or investigational drugs, classified as agents directly targeting the virus ( Figure 1 and Table 1 ) and those used to treat the respiratory distress and inflammation associated with the cytokine release syndrome ( Figure 2 and Table 2 ). abstract: On March 11, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) a global pandemic. As of July 2020, SARS-CoV-2 has infected more than 14 million people and provoked more than 590,000 deaths, worldwide. From the beginning, a variety of pharmacological treatments has been empirically used to cope with the life-threatening complications associated with Corona Virus Disease 2019 (COVID-19). Thus far, only a couple of them and not consistently across reports have been shown to further decrease mortality, respect to what can be achieved with supportive care. In most cases, and due to the urgency imposed by the number and severity of the patients’ clinical conditions, the choice of treatment has been limited to repurposed drugs, approved for other indications, or investigational agents used for other viral infections often rendered available on a compassionate-use basis. The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. In several months, an exceptionally large number of clinical trials have been designed to evaluate the safety and efficacy of anti-COVID-19 therapies in different clinical settings (treatment or pre- and post-exposure prophylaxis) and levels of disease severity, but only few of them have been completed so far. This review focuses on the molecular mechanisms of action that have provided the scientific rationale for the empirical use and evaluation in clinical trials of structurally different and often functionally unrelated drugs during the SARS-CoV-2 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32710969/ doi: 10.1016/j.bcp.2020.114169 id: cord-277253-vy0mvzeb author: Liu, Hongbo title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 words: 2265.0 sentences: 154.0 pages: flesch: 52.0 cache: ./cache/cord-277253-vy0mvzeb.txt txt: ./txt/cord-277253-vy0mvzeb.txt summary: title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. Inspired by the previous studies, several covalent inhibitors were experimentally identified to inhibit the 3CL pro activity and viral replication of SARS-CoV-2, and some of the complex crystal structures were solved [14, 15] . baicalensis inhibits SARS-CoV-2 3CL pro activity and the most active ingredient baicalein exhibits an IC50 of 0.39 M. We also identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL pro activity at microM concentration. baicalensis and tested its inhibitory activity against SARS-CoV-2 3CL pro . baicalensis extract at different concentrations on SARS-CoV-2 3CL pro activity were 6 shown in Figure 1A . abstract: COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CLpro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root of Scutellaria baicalensis has been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts of S. baicalensis have exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredient compounds. We found that the ethanol extract of S. baicalensis inhibits SARS-CoV-2 3CLpro activity in vitro and the replication of SARS-CoV-2 in Vero cells with an EC50 of 0.74 μg/ml. Among the major components of S. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CLpro activity with an IC50 of 0.39 μM. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. Our study demonstrates that the extract of S. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. url: https://doi.org/10.1101/2020.04.10.035824 doi: 10.1101/2020.04.10.035824 id: cord-353484-q7d0ysbo author: Liu, Xue title: COVID-19: Progress in diagnostics, therapy and vaccination date: 2020-06-19 words: 8557.0 sentences: 465.0 pages: flesch: 41.0 cache: ./cache/cord-353484-q7d0ysbo.txt txt: ./txt/cord-353484-q7d0ysbo.txt summary: Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic. Another type of rapid diagnostic test (RDT) that detects the presence of viral antigens expressed by SARS-CoV-2 virus in a respiratory tract sample is of low complexity and may provide results typically within 30 minutes [68, 69] . Studies in Vero E6 cells have suggested that favipiravir can cripple the SARS-CoV-2 virus (EC50 = 61.88 μM) [88] , and patients with COVID-19 are being recruited in randomized trials to evaluate the efficacy of favipiravir plus other antivirals (e.g., ClinicalTrials.gov: ChiCTR2000029600, ChiCTR2000029544). As no specific therapeutic agents or vaccines are available for COVID-19, this therapy is the only strategy that is immediately available for use to prevent and treat a novel, emerging infectious disease such as SARS-CoV-2 infection [121, 122] . abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently become a pandemic. As the sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and the economy, the development of strategies to contain the virus's spread are urgently needed. At present, various diagnostic kits to test for SARS-CoV-2 are available for use to initiate appropriate treatment faster and to limit further spread of the virus. Several drugs have demonstrated in vitro activity against SARS-CoV-2 or potential clinical benefits. In addition, institutions and companies worldwide are working tirelessly to develop treatments and vaccines against COVID-19. However, no drug or vaccine has yet been specifically approved for COVID-19. Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic. url: https://doi.org/10.7150/thno.47987 doi: 10.7150/thno.47987 id: cord-319194-ukuia48s author: Liò, Pietro title: Phylogenomics and bioinformatics of SARS-CoV date: 2004-02-04 words: 4488.0 sentences: 201.0 pages: flesch: 45.0 cache: ./cache/cord-319194-ukuia48s.txt txt: ./txt/cord-319194-ukuia48s.txt summary: Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. Figure 1 shows the maximum likelihood tree produced using a set of homologous replicases from five SARS-CoV strains, 12 other coronaviruses representing both groups 1 and 2 of the genus [2, 3] , one torovirus (Breda virus) and one okavirus [yellow head (YH) virus], which were determined to most closely represent the consensus coronavirus sequence by a PSI-Blast search [12] . abstract: Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The topology and branch lengths of the phylogenetic relationships among the family Coronaviridae, including SARS-CoV, have been estimated using the replicase polyprotein. The spike protein fragments S1 (involved in receptor-binding) and S2 (involved in membrane fusion) have been found to have different mutation rates. Fragment S1 can be further divided into two regions (S1A, which comprises approximately the first 400 nucleotides, and S1B, comprising the next 280) that also show different rates of mutation. The phylogeny presented on the basis of S1B shows that SARS-CoV is closely related to MHV (murine hepatitis virus), which is known to bind the murine receptor CEACAM1. The predicted structure, accessibility and mutation rate of the S1B region is also presented. Because anti-SARS drugs based on S2 heptads have short half-lives and are difficult to manufacture, our findings suggest that the S1B region might be of interest for anti-SARS drug discovery. url: https://api.elsevier.com/content/article/pii/S0966842X04000216 doi: 10.1016/j.tim.2004.01.005 id: cord-266987-ikt8r2o1 author: Loeffelholz, Michael J. title: Laboratory diagnosis of emerging human coronavirus infections – the state of the art date: 2020-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32196430/ doi: 10.1080/22221751.2020.1745095 id: cord-263481-w5ytp1q7 author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach date: 2020-06-02 words: 3013.0 sentences: 171.0 pages: flesch: 54.0 cache: ./cache/cord-263481-w5ytp1q7.txt txt: ./txt/cord-263481-w5ytp1q7.txt summary: MERS-CoV uses dipeptidyl peptidase-4 (DPP4) as entry receptor [11] whereas SARS-CoV and SARS-CoV-2 utilize ACE-2 (angiotensin converting enzyme-2) [12] , abundantly available in lung alveolar epithelial cells and enterocytes, suggesting S glycoprotein as a potential drug target to halt the entry of SARS-with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. abstract: The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure. url: https://www.sciencedirect.com/science/article/pii/S1567134820302203?v=s5 doi: 10.1016/j.meegid.2020.104389 id: cord-343517-vf32wxkx author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 words: 2745.0 sentences: 163.0 pages: flesch: 53.0 cache: ./cache/cord-343517-vf32wxkx.txt txt: ./txt/cord-343517-vf32wxkx.txt summary: However, SARS-CoV-2 has emerged with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. The evolutionary distances showed that all the SARS-CoV-2 spike proteins cluster in the same node of the phylogenetic tree confirming the sequences are similar to Refseq YP_009724390 (Fig. 2) . abstract: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation. url: https://doi.org/10.1101/2020.04.07.030924 doi: 10.1101/2020.04.07.030924 id: cord-334313-v2syspu6 author: Long, S. Wesley title: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date: 2020-05-03 words: 4525.0 sentences: 251.0 pages: flesch: 48.0 cache: ./cache/cord-334313-v2syspu6.txt txt: ./txt/cord-334313-v2syspu6.txt summary: We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. Because in vitro resistance of SARS-CoV to remdesivir has been reported to be caused by either of two amino acid replacements in RdRp (Phe476Leu and Val553Leu), we interrogated our data for polymorphisms in the nsp12 gene. abstract: We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. These genomes were from the viruses causing infections in the earliest recognized phase of the pandemic affecting Houston. Substantial viral genomic diversity was identified, which we interpret to mean that the virus was introduced into Houston many times independently by individuals who had traveled from different parts of the country and the world. The majority of viruses are apparent progeny of strains derived from Europe and Asia. We found no significant evidence of more virulent viral types, stressing the linkage between severe disease, underlying medical conditions, and perhaps host genetics. We discovered a signal of selection acting on the spike protein, the primary target of massive vaccine efforts worldwide. The data provide a critical resource for assessing virus evolution, the origin of new outbreaks, and the effect of host immune response. Significance COVID-19, the disease caused by the SARS-CoV-2 virus, is a global pandemic. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. We identified no evidence that a particular strain or its progeny causes more severe disease, underscoring the connection between severe disease, underlying health conditions, and host genetics. Some amino acid replacements in the spike protein suggest positive immune selection is at work in shaping variation in this protein. Our analysis traces the early molecular architecture of SARS-CoV-2 in Houston, and will help us to understand the origin and trajectory of future infection spikes. url: https://doi.org/10.1101/2020.05.01.072652 doi: 10.1101/2020.05.01.072652 id: cord-287658-c2lljdi7 author: Lopez-Rincon, Alejandro title: Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date: 2020-09-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from available repositories, separating the genome of different virus strains from the Coronavirus family with considerable accuracy. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets on existing datasets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from NGDC, separating the genome of different virus strains from the Coronavirus family with accuracy 98.73%. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. The proposed methodology has a substantial added value over existing methods, as it is able to both identify promising primer sets for a virus from a limited amount of data, and deliver effective results in a minimal amount of time. Considering the possibility of future pandemics, these characteristics are invaluable to promptly create specific detection methods for diagnostics. url: https://doi.org/10.1101/2020.03.13.990242 doi: 10.1101/2020.03.13.990242 id: cord-314051-dr27bsvt author: Lother, Sylvain A. title: Preoperative SARS-CoV-2 screening: Can it really rule out COVID-19? date: 2020-06-23 words: 3121.0 sentences: 259.0 pages: flesch: 56.0 cache: ./cache/cord-314051-dr27bsvt.txt txt: ./txt/cord-314051-dr27bsvt.txt summary: If viral carriage is not detected by testing, patients may proceed with elective surgery whereby signs and symptoms of coronavirus disease (COVID-19) may arise in the postoperative period, leading to adverse outcomes. 3 While screening with RT-PCR may detect some presymptomatic preoperative patients, the window of diagnostic utility is small, and careful interpretation of negative and positive test results must be considered prior to altering the course of therapy. A positive RT-PCR result identifies a group of patients who may be infected with SARS-CoV-2 and should have elective surgeries delayed. Si la présence virale n''est pas dépistée par un test, les patients peuvent aller de l''avant avec leur chirurgie non urgente, à la suite de laquelle les signes et symptômes d''une atteinte au coronavirus (COVID-19) pourraient survenir en période postopératoire, entraînant des devenirs défavorables. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32578049/ doi: 10.1007/s12630-020-01746-w id: cord-297599-y4lu8m4k author: Luo, Hua title: Anti-COVID-19 drug screening: Frontier concepts and core technologies date: 2020-10-28 words: 7665.0 sentences: 373.0 pages: flesch: 44.0 cache: ./cache/cord-297599-y4lu8m4k.txt txt: ./txt/cord-297599-y4lu8m4k.txt summary: This paper thoroughly summarizes interdisciplinary notions and techniques, including disease model, biochip, network pharmacology, and molecular docking technology, etc., providing a reference for researchers in the screening of drugs for COVID-19 prevention and treatment. Some researchers are currently using mice as an animal model to test drugs and vaccines and to investigate the nature of the infection of SARS-CoV-2 [49] [50] [51] . In fact, in a study led by Qin Chuan on SARS, engineered mice that could express human ACE2 protein was successfully established, leading this Chinese team pioneered the establishment of a SARS-CoV-2 infected hACE2 transgenic mouse model [54] . For example, an effective and convenient novel mouse model in evaluating in vivo protective capacity of the SARS-CoV-2 vaccines was developed through stitching the human gene for ACE2 into an adenovirus by Perlman et al. abstract: The outbreak of COVID-19 has recently evolved into a global pandemic. Up to July 2020, almost every country has confirmed COVID-19 cases reported worldwide. Many leading experts have predicted that the epidemic will persist for relatively a long period of time. Thus far, there have been no remedies proven effective against the disease. As the nation where COVID-19 broke out first, China has adopted a combination of traditional Chinese medicine and western medicine to fight against the disease, and has achieved significant clinical result. Up to now, the COVID-19 pandemic has been effectively controlled in China. However, the rest of the world (except for a limited number of countries and regions) is still in deep water. This paper thoroughly summarizes interdisciplinary notions and techniques, including disease model, biochip, network pharmacology, and molecular docking technology, etc., providing a reference for researchers in the screening of drugs for COVID-19 prevention and treatment. These methodologies may facilitate researchers to screen out more potential drugs for treating COVID-19 pneumonia and to tackle this global crisis. url: https://www.ncbi.nlm.nih.gov/pubmed/33133232/ doi: 10.1186/s13020-020-00393-z id: cord-336057-tj9qcuf8 author: Lv, Yantian title: No intrauterine vertical transmission in pregnancy with COVID-19: a case report date: 2020-08-05 words: 1338.0 sentences: 88.0 pages: flesch: 59.0 cache: ./cache/cord-336057-tj9qcuf8.txt txt: ./txt/cord-336057-tj9qcuf8.txt summary: The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. Amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were collected during the operation and tested for the SARS-COV-2 nucleic acid, and the mother and infant were separated after the operation. In addition, not only SARS-COV-2 nucleic acid test results were negative in 4 times pharyngeal swabs, but also the anal swab, amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were negative. Li 9 also reported a 35-week pregnant woman with COVID-19, whose amniotic fluid, cord blood and placenta, breast milk samples as well as neonates swab SARS-COV-2 nucleic acid were all negative. abstract: Abstract The coronavirus disease 2019(COVID-19)has been a worldwide pandemic diseases, nearly 400,000 people died at now. The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. The SARS-COV-2 nucleic acid test results of these specimens were negative. there is no evidence of intrauterine vertical transmission during delivery in the third trimester, but the data are limited and need to be further explored. url: https://api.elsevier.com/content/article/pii/S1341321X2030266X doi: 10.1016/j.jiac.2020.07.015 id: cord-305587-xtqvtleb author: Ma, Cuiqing title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date: 2020-05-11 words: 2310.0 sentences: 122.0 pages: flesch: 40.0 cache: ./cache/cord-305587-xtqvtleb.txt txt: ./txt/cord-305587-xtqvtleb.txt summary: Identification and characterization of novel neutralizing epitopes in the 506 receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated 507 SARS-CoV vaccine Intranasal vaccination of recombinant adeno-associated virus 533 encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces 534 strong mucosal immune responses and provides long-term protection against SARS-CoV infection Receptor-binding domain of SARS-CoV spike protein induces highly 556 potent neutralizing antibodies: implication for developing subunit vaccine Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies 613 primarily targeting the receptor binding region Receptor-binding domain of severe acute respiratory syndrome coronavirus 621 spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. Cross-neutralization of human and palm civet severe acute 636 respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein abstract: The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics. url: https://api.elsevier.com/content/article/pii/S1286457920300824 doi: 10.1016/j.micinf.2020.05.004 id: cord-269289-6uog10j4 author: Mabillard, Holly title: Electrolyte Disturbances in SARS-CoV-2 Infection date: 2020-07-22 words: 5684.0 sentences: 289.0 pages: flesch: 44.0 cache: ./cache/cord-269289-6uog10j4.txt txt: ./txt/cord-269289-6uog10j4.txt summary: These include additional respiratory complications (pulmonary fibrosis -reported in 21% of those hospitalised with SARS-CoV-2 9 months post-discharge in one study 3 ) 7 , cardiovascular complications (acute cardiac injury (7% 8 ), cardiomyopathy (1/3 patients 9 ), cardiac tamponade, heart failure, dysrhythmias (17% 8 ) and venous thromboembolic events (20% 10 )) 11 , neurological complications (myopathy, acute stroke (5.7% of those with severe infection 12 ), Guillain-Barre syndrome (0.4% hospitalised patients 11 ) and encephalopathy) 13 , acute liver and/or pancreatic injury (29% and 17% respectively in one cohort) 14 , cytokine storm syndrome, septic shock, DIC, diarrhoea, Kawasaki-like disease 14 and renal complications (acute tubular injury, rhabdomyolysis, proteinuria, secondary focal segmental glomerulosclerosis and possible renin-angiotensinaldosterone system activation) 15 . The study reported that the degree of hypokalaemia correlated with severity of SARS-CoV-2 symptoms and they suggested that hypokalaemia can be difficult to correct as seen in two patients because the renal potassium wasting persists until clinical recovery from the virus. abstract: The global pandemic secondary to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to unprecedented global morbidity and mortality. With a bewildering array of complications, renal involvement in various forms is common, including serum electrolyte derangements. Hypokalaemia secondary to SARS-CoV-2 was common in a reported Chinese cohort. Here we review the emerging evidence on hypokalaemia and SARS-CoV-2 infection, the potential pathophysiological mechanisms based on early clinical and histopathological data and important clinical implications. Mechanisms of hypokalaemia are multifactorial and so the electrolyte disturbance can be difficult to avoid. We provide further support to the theory of renin-angiotensin-aldosterone (RAS) activation, discuss the strengths and weaknesses of implicating RAS involvement and highlight the importance of calculating the transtubular potassium gradient to identify those at risk of hypokalaemia and its complications. url: https://www.ncbi.nlm.nih.gov/pubmed/33093945/ doi: 10.12688/f1000research.24441.2 id: cord-009476-4emc4o6n author: Madani, Tariq A title: Case definition and management of patients with MERS coronavirus in Saudi Arabia date: 2014-09-22 words: 1014.0 sentences: 47.0 pages: flesch: 36.0 cache: ./cache/cord-009476-4emc4o6n.txt txt: ./txt/cord-009476-4emc4o6n.txt summary: 16 outbreak and prevent human-to-human and animalto-human transmission; an appropriate management algorithm, including best-practice guidelines for accurate diagnosis, infection control, intensive care, emergency medicine, and treatment; prioritise research related to the MERS-CoV outbreak such as case-control and cohort studies, seroprevalence studies, and clinical trials; and to eff ectively monitor outbreak control activities. 2 The new case defi nition (appendix) was developed based on reported health-care-associated MERS-CoV pneumonia (added as category 2 in the new case defi nition) and non-respiratory characteristics of patients with confi rmed infection who fi rst presented with acute febrile dengue-like illness with body aches, leucopenia, and thrombocytopenia (added as category 3). WHO Revised interim case defi nition for reporting to WHO-Middle East respiratory syndrome coronavirus (MERS-CoV): as of First confi rmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and Public Health Authorities abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158994/ doi: 10.1016/s1473-3099(14)70918-1 id: cord-258312-3v5t4k8d author: Majachani, Nicole title: A Case of a Newborn Baby Girl Infected with SARS-CoV-2 Due to Transplacental Viral Transmission date: 2020-10-25 words: 1962.0 sentences: 131.0 pages: flesch: 51.0 cache: ./cache/cord-258312-3v5t4k8d.txt txt: ./txt/cord-258312-3v5t4k8d.txt summary: Patient: Female, 31-year-old Final Diagnosis: COVID-19 • SARS-CoV-2 Symptoms: Asymptomatic Medication:— Clinical Procedure: — Specialty: Pediatrics and Neonatology OBJECTIVE: Unusual clinical course BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus and is responsible for the current pandemic. CASE REPORT: 31-year-old Hispanic woman in the final week of pregnancy developed mild respiratory symptoms of COVID-19 pneumonia and tested positive for SARS-CoV-2 infection. In response to the potential risks to both the mother and fetus, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control have developed guidelines which provide a framework for detecting infections early and preventing potential transmission of SARS-CoV-2. Although similar viruses like severe acute respiratory syndrome coronavirus 1 have not demonstrated the ability to cause fetal infection, SARS-CoV-2 is able to bind ACE2 with much higher affinity [11] , thus increasing the probability of transplacental transmission. abstract: Patient: Female, 31-year-old Final Diagnosis: COVID-19 • SARS-CoV-2 Symptoms: Asymptomatic Medication:— Clinical Procedure: — Specialty: Pediatrics and Neonatology OBJECTIVE: Unusual clinical course BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus and is responsible for the current pandemic. It mainly infects cells of the lower respiratory tract and has been linked to severe respiratory complications. Although multiple routes of transmission have been reported in the literature, there is no definitive evidence for transplacental transmission. We present a case of neonatal SARS-CoV-2 likely due to transplacental transmission. CASE REPORT: 31-year-old Hispanic woman in the final week of pregnancy developed mild respiratory symptoms of COVID-19 pneumonia and tested positive for SARS-CoV-2 infection. She had a history of Human immunodeficiency virus (HIV) infection and gestational diabetes. Two days later, she gave birth to a baby girl who tested positive for SARS-CoV-2 on the first day after birth. She was delivered via elective cesarean section adhering to a strict infection control protocol. CONCLUSIONS: This report presents a case of a 31-year-old mother with mild symptoms of COVID-19 pneumonia who was positive for SARS-CoV-2 infection and who gave birth to a baby girl who was also positive for SARS-CoV-2. This case supports the possibility of transplacental transmission of SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/33099570/ doi: 10.12659/ajcr.925766 id: cord-292152-gmru83ac author: Makrinioti, Heidi title: Intussusception in two children with SARS-CoV-2 infection in children date: 2020-08-08 words: 1752.0 sentences: 109.0 pages: flesch: 45.0 cache: ./cache/cord-292152-gmru83ac.txt txt: ./txt/cord-292152-gmru83ac.txt summary: This report compares intussusception as likely associated with SARS-CoV-2 infection in infants that presented in Wuhan and London. Based on the data so far, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in children is shown to run a milder course with lower reported mortality rates (1, 2) . However, as the definition of suspected cases does not include presentations with gastrointestinal symptoms only, there is still no clear answer to the question "should we screen for SARS-CoV-2 infection in children who require admission to hospital with gastrointestinal symptoms?". In addition to the fact that most of the presentations of the infection in children are atypical, there is very recent evidence showing that the highest viral shedding is taking place 2 to 3 days before onset of symptoms (https://www.nature.com/articles/s41591-020-0869-5). This brief report describes two cases of intussusception in infants found to be positive with SARS-CoV-2. This report describes two infants with intussusception and SARS-CoV-2 infection. abstract: This report compares intussusception as likely associated with SARS-CoV-2 infection in infants that presented in Wuhan and London. While the intussusception was reduced by enemas in Wuhan, the outcome was fatal. Whereas the intussusception was not reduced by enemas in London and required surgery, the outcome was favourable. url: https://doi.org/10.1093/jpids/piaa096 doi: 10.1093/jpids/piaa096 id: cord-255815-5d9bqji0 author: Malik, Ajamaluddin title: MERS‐CoV papain-like protease (PL(pro)): expression, purification, and spectroscopic/thermodynamic characterization date: 2017-05-30 words: 3925.0 sentences: 243.0 pages: flesch: 59.0 cache: ./cache/cord-255815-5d9bqji0.txt txt: ./txt/cord-255815-5d9bqji0.txt summary: An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. In a similar experiment, MERS-CoV PL pro was gradually heated from 20 to 80°C at a rate of 1°C/min during which tryptophan fluorescence was measured by exciting at 295 nm and collecting at 330 and 350 nm to obtain the temperature melting curve. Commonly, protein unfolding fluorescence spectra are characterized by a long wavelength shift ''''red-shift.'''' But some proteins, Fig. 2 a Sequence of C-terminal His-tagged MERS-CoV PL pro showing ten Tyr and five Trp residues, which are highlighted in green and blue, respectively. Our result showed that the band intensity of the supernatant samples incubated from 20 to 70°C was apparently unchanged (Fig. 5) , indicating Fig. 3 Thermally induced structural changes in MERS-CoV PL pro as monitored by the intrinsic tryptophan fluorescence spectroscopy. abstract: Within a decade, MERS-CoV emerged with nearly four times higher case fatality rate than an earlier outbreak of SARS-CoV and spread out in 27 countries in short span of time. As an emerging virus, combating it requires an in-depth understanding of its molecular machinery. Therefore, conformational characterization studies of coronavirus proteins are necessary to advance our knowledge of the matter for the development of antiviral therapies. In this study, MERS-CoV papain-like protease (PL(pro)) was recombinantly expressed and purified. Thermal folding pathway and thermodynamic properties were characterized using dynamic multimode spectroscopy (DMS) and thermal shift assay. DMS study showed that the PL(pro) undergoes a single thermal transition and follows a pathway of two-state folding with T (m) and van’t Hoff enthalpy values of 54.4 ± 0.1 °C and 317.1 ± 3.9 kJ/mol, respectively. An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. Our findings provide significant understandings of the thermodynamic and structural properties of MERS-CoV PL(pro). url: https://doi.org/10.1007/s13205-017-0744-3 doi: 10.1007/s13205-017-0744-3 id: cord-335122-8s3bcyo8 author: Marshall, Steve title: COVID-19: What do we know? date: 2020-09-21 words: 5249.0 sentences: 375.0 pages: flesch: 41.0 cache: ./cache/cord-335122-8s3bcyo8.txt txt: ./txt/cord-335122-8s3bcyo8.txt summary: 44, 45, [47] [48] [49] The amount of viable SARS-CoV-2 in droplet nuclei remains unclear, but in subjects infected with other respiratory viruses, such as influenza, experiments comparing coughing and breathing suggest an equivalent production of viral RNA and replication-competent virus, detected at close range (< 12 inches). 78 In situations where healthcare workers wearing personal protective equipment (PPE) attend to patients with COVID-19 and do not perform medical AGPs, direct airborne transmission of replicationcompetent SARS-CoV-2 has not been confirmed. 79 The results of hospital studies evaluating aerosolization of body fluids and respiratory droplets of SARS-CoV-1 infected patients generated during certain medical AGPs (tracheal intubation, non-invasive ventilation, bronchoscopy, etc.), suggest that airborne transmission of SARS-CoV-2 may be possible during these procedures. Currently there are no studies reporting airborne viable (replication-competent) SARS-CoV-2 virus J o u r n a l P r e -p r o o f in hospital settings where infected patients are cared for, but not subjected to medical AGPs, by healthcare workers wearing surgical masks. abstract: Evidence regarding provision of orthodontic care during COVID-19 pandemic is examined. url: https://www.sciencedirect.com/science/article/pii/S0889540620305758?v=s5 doi: 10.1016/j.ajodo.2020.08.010 id: cord-291436-cu5o8ipw author: Martínez-Hernández, Fernando title: Assessing the SARS-CoV-2 threat to wildlife: Potential risk to a broad range of mammals date: 2020-10-05 words: 2947.0 sentences: 176.0 pages: flesch: 57.0 cache: ./cache/cord-291436-cu5o8ipw.txt txt: ./txt/cord-291436-cu5o8ipw.txt summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect animals, however, the whole range of potential hosts is still unknown. This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) —both recognized as receptors and protease for coronavirus spike protein— and the genetic variation of the viral protein spike in the recognition sites. Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is causing the biggest pandemic 52 of this century, and could potentially infect between 30 to 40% of the world''s populations (De 53 Soto et al., 2020) . Due to its high transmission rate and mortality, researches around the world 54 are trying to get some insight about its origin through the analysis of related-virus genes 55 sequences in humans and animals (Lu R et al., 2020) , and looking for Angiotensin-Converting 56 abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect animals, however, the whole range of potential hosts is still unknown. This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) —both recognized as receptors and protease for coronavirus spike protein— and the genetic variation of the viral protein spike in the recognition sites. The sequences from different mammals, birds, reptiles, and amphibians, and the sequence from SARS-CoV-2 S protein were obtained from the GenBank. Comparisons of aligned sequences were made by selecting amino acids residues of ACE2, TMPRSS2 and S protein; phylogenetic trees were reconstructed using the same sequences. The species susceptibility was ranked by substituting the values of amino acid residues for both proteins. Our results ranked primates at the top, but surprisingly, just below are carnivores, cetaceans and wild rodents, showing a relatively high potential risk, as opposed to lab rodents that are typically mammals at lower risk. Most of the sequences from birds, reptiles and amphibians occupied the lowest ranges in the analyses. Models and phylogenetic trees outputs showed the species that are more prone to getting infected with SARS-CoV-2. Interestingly, during this short pandemic period, a high haplotypic variation was observed in the RBD of the viral S protein, suggesting new risks for other hosts. Our findings are consistent with other published results reporting laboratory and natural infections in different species. Finally, urgent measures of wildlife monitoring are needed regarding SARS-CoV-2, as well as measures for avoiding or limiting human contact with wildlife, and precautionary measures to protect wildlife workers and researchers; monitoring disposal of waste and sewage than can potentially affect the environment, and designing protocols for dealing with the outbreak. url: https://api.elsevier.com/content/article/pii/S2530064420300596 doi: 10.1016/j.pecon.2020.09.008 id: cord-318934-dxipu00r author: Matsuyama, Shutoku title: Enhancement of SARS-CoV Infection by Proteases date: 2006 words: 1861.0 sentences: 109.0 pages: flesch: 56.0 cache: ./cache/cord-318934-dxipu00r.txt txt: ./txt/cord-318934-dxipu00r.txt summary: Moreover, SARS-CoV entry from the cell surface mediated by proteases was a 100-fold more efficient infection than entry through endosomes. However, no S2 band was detected in SARS-CoV infected cells treated with proteases that failed to induce fusion. 3 stated that SARS-CoV is able to enter cells directly from their surface, if receptor-bound virus is treated with trypsin and other proteases that induce fusion. Treatment of VeroE6 cells with bafilomycin was shown to suppress SARS-CoV infection via the endosomal pathway to less than 1/100 (Fig. 2) . Pseudotype VSV bearing SARS-CoV S protein infection was also facilitated in bafilomycin-treated VeroE6 cells after treatment with proteases that induce fusion of SARS-CoV infected cells. These observations suggest that proteases that facilitate SARS-CoV entry from the cell surface support efficient SARS-CoV infection. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/17037538/ doi: 10.1007/978-0-387-33012-9_42 id: cord-331193-33cyvidx author: Mawhinney, Jamie A title: Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode date: 2020-06-14 words: 2512.0 sentences: 161.0 pages: flesch: 50.0 cache: ./cache/cord-331193-33cyvidx.txt txt: ./txt/cord-331193-33cyvidx.txt summary: Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. [9] [10] [11] [12] This article outlines a case of COVID-19 presenting with an acute manic episode necessitating emergency intubation and discusses potential mechanisms for the development of neuropsychiatric disease. ► The neuroinvasive potential of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (neurotropism) has been reported, but the pathophysiology remains unclear with uncertainty over its long-term consequences. abstract: A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient’s mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid. url: https://doi.org/10.1136/bcr-2020-236123 doi: 10.1136/bcr-2020-236123 id: cord-292742-mio4przi author: McAloose, Denise title: From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo date: 2020-10-13 words: 6364.0 sentences: 309.0 pages: flesch: 47.0 cache: ./cache/cord-292742-mio4przi.txt txt: ./txt/cord-292742-mio4przi.txt summary: KEYWORDS One Health, Panthera leo, Panthera tigris, SARS-CoV-2, in situ hybridization, lion, rRT-PCR, tiger, virus isolation, whole-genome sequencing, zoo, zoonotic infection C oronaviruses are a recognized cause of disease in humans and animals (1) . Subsequent to confirmation of SARS-CoV-2 infection in the animals, an epidemiologic investigation of zoo staff identified 10 zoo keepers and two managers who provided care for and had close (Յ1.8-m) but not direct contact with the tigers or lions between 16 March 2020 (the date on which the zoo was closed to the public due to the pandemic) and 27 March to 3 April 2020 (timeline of disease onset in the animals). Nine complete SARS-CoV-2 genome sequences (from four tigers, three lions, and two keepers) and eight full-length S gene sequences (from seven symptomatic animals and one asymptomatic animal) were generated directly from respiratory and/or fecal samples (Data Sets 3 and 4). abstract: Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species. url: https://doi.org/10.1128/mbio.02220-20 doi: 10.1128/mbio.02220-20 id: cord-256737-ptjng78b author: McBride, Corrin E. title: Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein date: 2010-09-01 words: 8233.0 sentences: 414.0 pages: flesch: 58.0 cache: ./cache/cord-256737-ptjng78b.txt txt: ./txt/cord-256737-ptjng78b.txt summary: The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Importantly, we show that SARS-CoV S palmitoylation is not necessary for efficient interaction with SARS-CoV M, which differs from published experiments for MHV (Thorp et al., 2006) and suggests a significant difference between the two viruses that may have important implications for virus assembly and infectivity. To determine if SARS-CoV S becomes palmitoylated in a pre-medial Golgi compartment, HEK293T cells exogenously expressing SARS-CoV S were labeled for 30 min with 35 S-methionine/ cysteine to measure total protein expression or 3 H-palmitic acid to measure palmitoylated protein. Although both SARS-CoV S and S PN were present at the cell surface, it is possible that there could be a difference in the amount of protein at the plasma membrane at steady state if palmitoylation affects a post-Golgi trafficking step. abstract: Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein, and may point to important differences in assembly and infectivity of these two coronaviruses. url: https://doi.org/10.1016/j.virol.2010.05.031 doi: 10.1016/j.virol.2010.05.031 id: cord-329010-n0mz098o author: McKee, Dwight L. title: Candidate drugs against SARS-CoV-2 and COVID-19 date: 2020-04-29 words: 5193.0 sentences: 260.0 pages: flesch: 41.0 cache: ./cache/cord-329010-n0mz098o.txt txt: ./txt/cord-329010-n0mz098o.txt summary: Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. Drugs that have recently been shown to target MERS-CoV in mice [15] , and to inhibit Ebola virus RdRP and SARS-CoV-2 proteases in humans, such as remdesivir and ritonavir/lopinavir, also constitute candidate drugs against SARS-CoV-2 and are now investigated for their therapeutic efficacy in COVID-19 patients in 2 international clinical trials (SOLIDARITY Trial and DisCoVeRy Trial). The emergence of the novel beta coronavirus SARS-CoV-2 from Wuhan, Hubei province, China in December 2019 rapidly led to a pandemic involving more than 2,500,000 infected persons and more proven drugs such as camostat mesilate which prevents virus host cell entry by inhibiting TMPRSS2 [8] , and chloroquine phosphate which inhibits terminal phosphorylation of ACE2, or hydroxychloroquine which is metabolized in vivo to chloroquine [44] . abstract: Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. url: https://www.sciencedirect.com/science/article/pii/S1043661820311671?v=s5 doi: 10.1016/j.phrs.2020.104859 id: cord-260048-yis26g81 author: McNamara, Ryan P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-10-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 is constantly evolving. Prior studies focused on high case-density locations, such as the U.S. Northern and Western metropolitan areas. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant, which was associated with higher genome copy numbers and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3’ untranslated region. The data are consistent with community spread within local populations and the larger continental U.S. The data instill confidence in current testing sensitivity and validate “testing by sequencing” as an option to uncover cases, particularly non-standard COVID-19 clinical presentations. This study contributes to the understanding of COVID-19 through an extensive set of genomes from a non-urban setting and informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. url: https://www.ncbi.nlm.nih.gov/pubmed/33113345/ doi: 10.1016/j.celrep.2020.108352 id: cord-314445-4cb4a9r5 author: McNamara, Ryan P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-06-19 words: 1960.0 sentences: 131.0 pages: flesch: 53.0 cache: ./cache/cord-314445-4cb4a9r5.txt txt: ./txt/cord-314445-4cb4a9r5.txt summary: This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. The current COVID-19 pandemic is an urgent public health emergency with over 112,000 deaths in the United States (U.S.) alone. At a CP ≥35 most positive samples still yielded reads that mapped to the target genome 227 and thus allowed detection of SARS-CoV-2 sequences; however, the results were less consistent, 228 and coverage was more variable. In sum, this study generated exhaustive SNV information representing the introduction and 325 spread of SARS-CoV-2 across a suburban low-density area in the Southern U.S. All samples were 326 from symptomatic cases and the majority of genomes clustered with variants that predominate the 327 outbreak in the U.S., rather than Europe or China. abstract: SARS-CoV-2 is constantly evolving. Prior studies have focused on high case-density locations, such as the Northern and Western metropolitan areas in the U.S. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant. The presence of D614G was associated with a higher genome copy number and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3’ untranslated region. The data are consistent with community spread within the local population and the larger continental U.S. No strain had mutations in the target sites used in common diagnostic assays. The data instill confidence in the sensitivity of current tests and validate “testing by sequencing” as a new option to uncover cases, particularly those not conforming to the standard clinical presentation of COVID-19. This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. url: https://doi.org/10.1101/2020.06.19.161141 doi: 10.1101/2020.06.19.161141 id: cord-281679-xmbnpawj author: Meekins, David A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 words: 3402.0 sentences: 191.0 pages: flesch: 46.0 cache: ./cache/cord-281679-xmbnpawj.txt txt: ./txt/cord-281679-xmbnpawj.txt summary: In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Cats, hamsters, and ferrets are highly susceptible to SARS-CoV-2 infection, demonstrate varying clinical and pathological disease manifestations, readily transmit the virus to naïve animals, and mount a virusspecific immune response [22] [23] [24] [25] [26] [27] [28] . Pigs are therefore unlikely to play an important role in the COVID-19 pandemic as a virus reservoir or as a pre-clinical animal model to study SARS-CoV-2 pathogenesis or develop novel countermeasures. abstract: The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics. url: https://doi.org/10.1101/2020.08.15.252395 doi: 10.1101/2020.08.15.252395 id: cord-322129-uyswj4ow author: Melin, Amanda D. title: Comparative ACE2 variation and primate COVID-19 risk date: 2020-10-27 words: 6310.0 sentences: 305.0 pages: flesch: 47.0 cache: ./cache/cord-322129-uyswj4ow.txt txt: ./txt/cord-322129-uyswj4ow.txt summary: Infection studies of rhesus monkeys, long-tailed macaques, and vervets as biomedical models have made it clear that at least some nonhuman primate species are permissive to SARS-CoV-2 infection and develop symptoms in response to infection that resemble those of humans following the development of COVID-19, including similar age-related effects [11] [12] [13] [14] [15] [16] . We assessed the variation at amino acid residues identified as critical for ACE2 recognition by the SARS-CoV-2 RBD and undertook an analysis of positive selection and protein modeling to gauge the potential for adaptive differences and the likely effects of protein variation. In particular, the twelve sites in the ACE2 protein that are critical for binding of the SARS-CoV-2 virus are invariant across the Catarrhini, which includes great apes, gibbons, and monkeys of Africa and Asia (Fig. 1) . abstract: The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species. url: https://www.ncbi.nlm.nih.gov/pubmed/33110195/ doi: 10.1038/s42003-020-01370-w id: cord-296268-kb7fgfaq author: Mendonça, Luiza title: SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date: 2020-11-05 words: 2647.0 sentences: 161.0 pages: flesch: 57.0 cache: ./cache/cord-296268-kb7fgfaq.txt txt: ./txt/cord-296268-kb7fgfaq.txt summary: Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Understanding the genome 27 replication, assembly and egress of SARS-CoV-2, a multistage process that involves different 28 cellular compartments and the activity of many viral and cellular proteins, is critically Krios to identify each individual infected cell (39.2 % for MOI of 0.1 and 45.4% for MOI 124 0.5) where cryoET tilt series were collected at the cell periphery. The grids were then 125 transferred to a FIB/SEM dualbeam instrument and the same infected cells were subjected to 126 either serial cryoFIB/SEM volume imaging (Zhu et al., 2021) or cryoFIB milling of cellular 127 lamellae where additional cryoET tilt series were collected (Sutton et al., 2020) . abstract: Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified recombinant viral components and inactivated viruses. However, investigation of the SARS-CoV-2 infection in the native cellular context is scarce, and there is a lack of comprehensive knowledge on SARS-CoV-2 replicative cycle. Understanding the genome replication, assembly and egress of SARS-CoV-2, a multistage process that involves different cellular compartments and the activity of many viral and cellular proteins, is critically important as it bears the means of medical intervention to stop infection. Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Our results reveal at the whole cell level profound cytopathic effects of SARS-CoV-2 infection, exemplified by a large amount of heterogeneous vesicles in the cytoplasm for RNA synthesis and virus assembly, formation of membrane tunnels through which viruses exit, and drastic cytoplasm invasion into nucleus. Furthermore, cryoET of cell lamellae reveals how viral RNAs are transported from double-membrane vesicles where they are synthesized to viral assembly sites; how viral spikes and RNPs assist in virus assembly and budding; and how fully assembled virus particles exit the cell, thus stablishing a model of SARS-CoV-2 genome replication, virus assembly and egress pathways. url: https://doi.org/10.1101/2020.11.05.370239 doi: 10.1101/2020.11.05.370239 id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 words: 4218.0 sentences: 237.0 pages: flesch: 44.0 cache: ./cache/cord-334220-sqvfr31q.txt txt: ./txt/cord-334220-sqvfr31q.txt summary: The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. abstract: In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) triggered by all the 28 proteins of SARS-CoV-2, or each single viral protein one-by-one. The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, an explorative network-based approach was applied to Bradykinin Storm, highlighting a possible direct action of ORF3a and NS7b to enhancing this condition. This network-based model for SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. url: https://doi.org/10.1101/2020.11.03.366666 doi: 10.1101/2020.11.03.366666 id: cord-283966-eln8ljjj author: Meyer, Benjamin title: Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013 date: 2014-04-17 words: 4017.0 sentences: 207.0 pages: flesch: 49.0 cache: ./cache/cord-283966-eln8ljjj.txt txt: ./txt/cord-283966-eln8ljjj.txt summary: Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases. Animals from the Arabian Peninsula had high neutralizing serum activities overall and reciprocal antibody titers <320-1,280, which support recent infection with MERS-CoV or a highly related virus. Expanding upon these studies, we used in the present study a recombinant MERS-CoV spike protein immunofluroescence assay (rIFA) augmented by a validated protein microarray (10, 21) , followed by MERS-CoV-specific neutralization assay, to screen 651 dromedary serum samples from the United Arabian Emirates. In the tested panel of camel serum samples, vIFA titers corresponded well to titers determined by rIFA and generally equal to or higher than titers in the rIFA (Table 1) To confirm results from affinity assays with results from a functional test, we determined endpoint virus neutralization titers by using a microneutralization test against MERS-CoV and BCoV. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein–specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV–neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases. url: https://doi.org/10.3201/eid2004.131746 doi: 10.3201/eid2004.131746 id: cord-274122-n9jnu2ah author: Mielech, Anna M. title: MERS-CoV papain-like protease has deISGylating and deubiquitinating activities date: 2014-02-01 words: 4845.0 sentences: 242.0 pages: flesch: 51.0 cache: ./cache/cord-274122-n9jnu2ah.txt txt: ./txt/cord-274122-n9jnu2ah.txt summary: Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. In this study, we demonstrate the deISGylating and deubiquitinating (DUB) activities of the papain-like protease from MERS-CoV, and provide new information on the potential role of coronavirus protease/DUBs to inhibit the innate immune response. Our results suggest that PLpro might contribute to the modulation of innate immune responses upon SARS-CoV and MERS-CoV infection, however, the exact mechanism and the role of coronavirus PLPs and their associated DUB and deISGylating activities in these processes remains to be determined. abstract: Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Here, we investigate the predicted DUB activity of the PLpro domain of the recently described Middle East Respiratory Syndrome Coronavirus (MERS-CoV). We found that expression of MERS-CoV PLpro reduces the levels of ubiquitinated and ISGylated host cell proteins; consistent with multifunctional PLpro activity. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. We show that expression of SARS-CoV and MERS-CoV PLpros blocks upregulation of cytokines CCL5, IFN-β and CXCL10 in stimulated cells. Overall these results indicate that the PLpro domains of MERS-CoV and SARS-CoV have the potential to modify the innate immune response to viral infection and contribute to viral pathogenesis. url: https://www.sciencedirect.com/science/article/pii/S0042682213006624 doi: 10.1016/j.virol.2013.11.040 id: cord-287847-rmhvc5n5 author: Miles, Brett A. title: Tracheostomy during SARS‐CoV‐2 pandemic: Recommendations from the New York Head and Neck Society date: 2020-04-20 words: 3458.0 sentences: 166.0 pages: flesch: 38.0 cache: ./cache/cord-287847-rmhvc5n5.txt txt: ./txt/cord-287847-rmhvc5n5.txt summary: Patients with significant medical comorbidities, acute respiratory distress syndrome/severe respiratory failure and a low chance of recovery who are infected with SARS-CoV-2 should be carefully evaluated, and discussions with family members, consultants, institutional ethics committees and the treating team should focus on overall prognosis and goals of care prior to performing tracheostomy as a routine matter of care. Although there are limited data on the current pandemic to fully inform personal protective equipment (PPE) recommendations, performing tracheostomy in an actively infected SARS-CoV-2 patient is certainly a high-risk procedure for health care workers. Techniques to manage the acute airway with endotracheal intubation, video laryngoscope for example, should be utilized if possible to avoid emergent tracheostomy in SARS-CoV-2 patients due to the high risk of unsafe conditions and health care worker contaminations. • When clinically appropriate, delay of tracheostomy procedures is recommended to allow for reduced viral load and to decrease the risk of nosocomial infection to critical health care providers. abstract: The rapid spread of SARS‐CoV‐2 in 2019 and 2020 has resulted in a worldwide pandemic characterized by severe pulmonary inflammation, effusions, and rapid respiratory compromise. The result of this pandemic is a large and increasing number of patients requiring endotracheal intubation and prolonged ventilator support. The rapid rise in endotracheal intubations coupled with prolonged ventilation requirements will certainly lead to an increase in tracheostomy procedures in the coming weeks and months. Performing tracheostomy in the setting of active SARS‐CoV‐2, when necessary, poses a unique situation, with unique risks and benefits for both the patient and the health care providers. The New York Head and Neck Society has collaborated on this document to provide guidance on the performance of tracheostomies during the SARS‐CoV‐2 pandemic. url: https://doi.org/10.1002/hed.26166 doi: 10.1002/hed.26166 id: cord-266156-xmf4emln author: Miller, Tyler E. title: Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital date: 2020-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The diagnosis of COVID‐19 requires integration of clinical and laboratory data. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS‐CoV‐2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. We conducted a single‐center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR‐positive SARS‐CoV‐2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70%‐71% from Days 9 to 11, and 30% at Day 21. To calculate daily clinical sensitivity by serology, we utilized 157 PCR‐positive patients with a total of 197 specimens tested by enzyme‐linked immunosorbent assay for IgM, IgG, and IgA anti‐SARS‐CoV‐2 antibodies. In contrast to PCR, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after Day 7, >80% after Day 12, and 100% by Day 21. Taken together, PCR and serology are complimentary modalities that require time‐dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32856766/ doi: 10.1096/fj.202001700rr id: cord-356166-fpno9zg5 author: Miyakawa, Kei title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles date: 2020-09-15 words: 1548.0 sentences: 94.0 pages: flesch: 52.0 cache: ./cache/cord-356166-fpno9zg5.txt txt: ./txt/cord-356166-fpno9zg5.txt summary: title: Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles However, a simple, convenient, rapid, and high-throughput test capable of directly detecting nAbs with high specificity, which could act as an ideal alternative to the neutralization assay, is yet to be developed (Ozcurumez et al., 2020) . In this report, we have developed a HiBiT-VLP-based neutralization test (hiVNT) that can readily detect SARS-CoV-2 nAbs ( Figure 1A ). We noticed a robust increase in NanoLuc activity when the LgBiT-expressing We next tested whether our newly developed hiVLP-SARS2 system could detect nAbs in the serum of COVID-19 patients. In this study, we established the hiVNT, a simple, high-throughput assay system for the quantitative and rapid determination of SARS-CoV-2 nAbs in the sera of individuals after recovery from symptomatic or subclinical COVID-19. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients'' B Cells abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32931563/ doi: 10.1093/jmcb/mjaa047 id: cord-275313-mfyff9ne author: Modjarrad, Kayvon title: Treatment strategies for Middle East respiratory syndrome coronavirus date: 2016-01-01 words: 3776.0 sentences: 174.0 pages: flesch: 40.0 cache: ./cache/cord-275313-mfyff9ne.txt txt: ./txt/cord-275313-mfyff9ne.txt summary: Most recently, Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a novel cause of severe acute respiratory illness after first being identified in a Saudi Arabian patient in 2012 [2] . Much of the work to develop safe and effective MERS-CoV countermeasures has centred on vaccines, but the relatively low prevalence of the disease, the sporadic nature of the case clusters and the dearth of detailed knowledge on chains of transmission highlight the need for greater investments into the discovery of effective therapeutic and secondary prophylactic regimens for infected and exposed individuals. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection abstract: Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations. url: https://www.ncbi.nlm.nih.gov/pubmed/26866060/ doi: nan id: cord-262786-otxpc46a author: Mohammadi, Soheil title: Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms date: 2020-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer’s disease, Parkinson’s disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement. url: https://www.ncbi.nlm.nih.gov/pubmed/32869183/ doi: 10.1007/s12035-020-02094-y id: cord-284068-sbon3aes author: Mok, Chee Keng title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 words: 1798.0 sentences: 104.0 pages: flesch: 49.0 cache: ./cache/cord-284068-sbon3aes.txt txt: ./txt/cord-284068-sbon3aes.txt summary: Validation assays to determine changes in infectious virus titres upon treatment was carried out by testing selected hit compounds in dose-dependent assays in Vero E6 to confirm the primary screen observation and also in the human hepatocarcinoma HuH7 cell line as the latter cell line expresses high levels of the ACE2 receptor (10) and supports replication of coronaviruses (11) . While recent data has shown that vitamin D levels are negatively associated with morbidity and mortality of COVID-19 cases (13, 14) , this is the first report of a direct inhibitory effect of calcitriol on SARS-CoV-2. The authors speculated that vitamin D supplementation could protect against SARS-CoV-2 infection and improve patient disease outcomes (16) , and our finding certainly provides credence to this hypothesis. Given the high transmissibility of SARS-CoV-2 globally (23), if these findings can be replicated in clinical trials, calcitriol may certainly prove to be an effective tool in the effort to control the pandemic while waiting for an effective vaccine to be rolled out globally. abstract: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients. url: https://doi.org/10.1101/2020.06.21.162396 doi: 10.1101/2020.06.21.162396 id: cord-340516-9dfaqsv7 author: Moore, Anne C. title: Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date: 2020-09-06 words: 6679.0 sentences: 335.0 pages: flesch: 48.0 cache: ./cache/cord-340516-9dfaqsv7.txt txt: ./txt/cord-340516-9dfaqsv7.txt summary: We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody. abstract: There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development. url: https://doi.org/10.1101/2020.09.04.283853 doi: 10.1101/2020.09.04.283853 id: cord-289407-8fje16z1 author: Moore, G. title: Detection of SARS-CoV-2 within the healthcare environment: a multicentre study conducted during the first wave of the COVID-19 outbreak in England date: 2020-09-25 words: 4720.0 sentences: 328.0 pages: flesch: 59.0 cache: ./cache/cord-289407-8fje16z1.txt txt: ./txt/cord-289407-8fje16z1.txt summary: Understanding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is spread within the hospital setting is essential if staff are to be adequately protected, effective infection control measures are to be implemented and nosocomial transmission is to be prevented. 6 Air samples taken during tracheostomy procedures, high flow nasal oxygen treatment, non-invasive ventilation and nebulisation have not contained SARS-CoV-2 RNA 7 and HCWs exposed to unrecognised COVID-19 patients undergoing similar high-risk AGPs have not become infected. . https://doi.org/10.1101/2020.09.24.20191411 doi: medRxiv preprint Several studies, utilising a range of air and surface sampling methods, have been carried out to determine the presence and prevalence of SARS-CoV-2 in the healthcare environment. [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] The detection of viral RNA in air samples differs with study with some reporting widespread airborne contamination 14, 18, 21 but many reporting low or non-detectable concentrations 13, 15, 16, 19 even in samples collected 10 cm from the face of positive patients. Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients abstract: Understanding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is spread within the hospital setting is essential if staff are to be adequately protected, effective infection control measures are to be implemented and nosocomial transmission is to be prevented. The presence of SARS-CoV-2 in the air and on environmental surfaces around hospitalised patients, with and without respiratory symptoms, was investigated. Environmental sampling was carried out within eight hospitals in England during the first wave of the COVID-19 outbreak. Samples were analysed using reverse transcription polymerase chain reaction (RT-PCR) and virus isolation assays. SARS-CoV-2 RNA was detected on 30 (8.9%) of 336 environmental surfaces. Ct values ranged from 28.8 to 39.1 equating to 2.2 x 105 to 59 genomic copies/swab. Concomitant bacterial counts were low, suggesting the cleaning performed by nursing and domestic staff across all eight hospitals was effective. SARS-CoV-2 RNA was detected in four of 55 air samples taken < 1 m from four different patients. In all cases, the concentration of viral RNA was low and ranged from < 10 to 460 genomic copies per m3 of air. Infectious virus was not recovered from any of the PCR positive samples analysed. Effective cleaning can reduce the risk of fomite (contact) transmission but some surface types may facilitate the survival, persistence and/or dispersal of SARS-CoV-2. The presence of low or undetectable concentrations of viral RNA in the air supports current guidance on the use of specific PPE ensembles for aerosol and non-aerosol generating procedures. url: http://medrxiv.org/cgi/content/short/2020.09.24.20191411v1?rss=1 doi: 10.1101/2020.09.24.20191411 id: cord-292256-jp80u828 author: Moriguchi, Takeshi title: A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 date: 2020-04-03 words: 1742.0 sentences: 121.0 pages: flesch: 53.0 cache: ./cache/cord-292256-jp80u828.txt txt: ./txt/cord-292256-jp80u828.txt summary: We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. (Wang et al., 2020a,b) A preliminary report warned that SARS-CoV-2 could have neuroinvasive potential because some patients showed neurologic symptoms such as headache, nausea, and vomiting . This brief report describes the first case of the patient, which brought in by the ambulance due to a convulsion accompanied by unconsciousness, was diagnosed with aseptic encephalitis with SARS-CoV-2 RNA in cerebrospinal fluid. This case shows the neuroinvasive potential of the virus and that we cannot exclude SARS-CoV-2 infections even if the RT-PCR test for SARS-CoV-2 using the patient''s nasopharyngeal specimen is negative. abstract: Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day 2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms. url: https://doi.org/10.1016/j.ijid.2020.03.062 doi: 10.1016/j.ijid.2020.03.062 id: cord-261566-fn08b0y2 author: Mudgal, Rajat title: Prospects for mucosal vaccine: shutting the door on SARS-CoV-2 date: 2020-09-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The sudden emergence of a highly transmissible and pathogenic coronavirus SARS-CoV-2 in December 2019 from China and its rapid global spread has posed an international health emergency. The rapid development of an effective vaccine is imperative to control the spread of SARS-CoV-2. A number of concurrent efforts to find an effective therapeutic agent or vaccine for COVID-19 (coronavirus disease 2019) are being undertaken globally. Oral and nasal mucosal surfaces serve as the primary portal of entry for pathogens like coronaviruses in the human body. As evidenced by studies on similar coronaviruses (SARS-CoV and MERS-CoV), mucosal vaccination can provide a safe and effective means for the induction of long-lasting systemic and mucosal immunity to confer protection against SARS-CoV-2. This article summarizes the approaches to an effective mucosal vaccine formulation which can be a rewarding approach to combat the unprecedented threat posed by this emerging global pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32931361/ doi: 10.1080/21645515.2020.1805992 id: cord-304073-f3iwclkm author: Mullick, Jhinuk Basu title: Animal Models to Study Emerging Technologies Against SARS-CoV-2 date: 2020-07-27 words: 5315.0 sentences: 322.0 pages: flesch: 50.0 cache: ./cache/cord-304073-f3iwclkm.txt txt: ./txt/cord-304073-f3iwclkm.txt summary: Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies. Non-human primates, Syrian hamsters, ferrets, cats, and engineered chimeras mimic the human infection more closely and hold strong potential as animal models of SARS-CoV-2 infection and progression of resulting human disease. Overall, the studies show that the Syrian hamster is a useful animal model for SARS-CoV-2 infection especially to study viral replication, shedding, and transmission through the respiratory tract. In all studies, animals developed NAbs. Overall, the rhesus macaque model has been similar in many aspects to the human COVID-19 pathogenesis. abstract: New technologies are being developed toward the novel coronavirus SARS-CoV-2 to understand its pathogenesis and transmission, to develop therapeutics and vaccines, and to formulate preventive strategies. Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies. Importantly, applications of traditional mice and rat models are limited for studying SARS-CoV-2 and development of COVID-19. Non-human primates, Syrian hamsters, ferrets, cats, and engineered chimeras mimic the human infection more closely and hold strong potential as animal models of SARS-CoV-2 infection and progression of resulting human disease. url: https://doi.org/10.1007/s12195-020-00638-9 doi: 10.1007/s12195-020-00638-9 id: cord-293988-f5gvwjyh author: Musso, Nicolò title: New SARS-CoV-2 Infection Detected in an Italian Pet Cat by RT-qPCR from Deep Pharyngeal Swab date: 2020-09-11 words: 3223.0 sentences: 186.0 pages: flesch: 54.0 cache: ./cache/cord-293988-f5gvwjyh.txt txt: ./txt/cord-293988-f5gvwjyh.txt summary: The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. In this study, a domestic cat with clear clinical signs of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. The World Health Organization (WHO) declared COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a worldwide pandemic [1] . As the cat''s pathology evolved rapidly and harmfully (the animal died in as little as three days), with clinical signs and rate of disease progression similar to human COVID-19 patients, and because previously published papers reported different cases of feline infection [10, [13] [14] [15] [16] , a nasal swab was collected in order to verify a possible infection with SARS-CoV-2. abstract: The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite close pet–human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear clinical signs of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study responding to the request of the scientific community to focus attention on the possible role of pets as a viral reservoir. An important question remains unanswered: did the cat actually die due to SARS-CoV-2 infection? url: https://www.ncbi.nlm.nih.gov/pubmed/32932800/ doi: 10.3390/pathogens9090746 id: cord-332448-5fz8ef4f author: Mutnal, M. B. title: Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses date: 2020-05-02 words: 2583.0 sentences: 159.0 pages: flesch: 55.0 cache: ./cache/cord-332448-5fz8ef4f.txt txt: ./txt/cord-332448-5fz8ef4f.txt summary: Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. . https://doi.org/10.1101/2020.04.30.20086116 doi: medRxiv preprint of this study is to encourage other laboratories to consider an early start to testing during pandemics, share 74 initial trends in this part of the world and possible impact of SARS-CoV-2 on other seasonal respiratory 75 This report describes the early trends of SARS-CoV-2 infections in the central and north Texas, 76 USA and impact of epidemiological interventions that may have led to the decrease in the incidence of was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. BSWH laboratory provided test results data on both ambulatory and inpatient 275 population, and shared patient demographics with local public health officials. abstract: Introduction: Rapid diagnosis and isolation are key to containing the rapid spread of a pandemic agent like SARS-CoV-2, which has spread globally since its initial outbreak in Wuhan province in China. SARS-CoV-2 is novel to most parts of the world including USA and the effect on normally prevalent viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March, 2020. Methods: This is a retrospective cohort study post launching of SARS-CoV-2 testing at BSWH, Temple TX. Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. Results: More than 3500 tests were performed during the first two weeks of testing for SARS-CoV-2 and identified 168 (4.7%) positive patients. Sixty-two (3.2%) of the 1,912 ambulatory patients and 106 (6.3%) of the 1,659 ED/inpatients were tested positive. Higher rate of infection (6.9%) were noted in the patients belonging to age group 25-34 years and least number of positive cases were noted in <25 years old (2%) group. The TX State county specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a sudden decrease in the occurrence of other infections due to seasonal viruses, perhaps due to increased epidemiological awareness, about SARS-CoV-2, among general public. Authors would also like to share a small study on SARS-CoV-2 serological assay for the detection of IgG antibodies. Conclusions: This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS-CoV-2. url: http://medrxiv.org/cgi/content/short/2020.04.30.20086116v1?rss=1 doi: 10.1101/2020.04.30.20086116 id: cord-287758-da11ypiy author: Mônica Vitalino de Almeida, Sinara title: COVID-19 therapy: what weapons do we bring into battle? date: 2020-09-10 words: 17412.0 sentences: 1034.0 pages: flesch: 45.0 cache: ./cache/cord-287758-da11ypiy.txt txt: ./txt/cord-287758-da11ypiy.txt summary: The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell. abstract: Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents. url: https://doi.org/10.1016/j.bmc.2020.115757 doi: 10.1016/j.bmc.2020.115757 id: cord-309147-c3ikb81g author: Nadeem, Muhammad Shahid title: Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) date: 2020-04-22 words: 4984.0 sentences: 315.0 pages: flesch: 51.0 cache: ./cache/cord-309147-c3ikb81g.txt txt: ./txt/cord-309147-c3ikb81g.txt summary: According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The recent reports have suggested that SARS-CoV-2 is a modified coronavirus of bat origin [22, 32] , which came to humans as a result of zoonotic transmission [33, 34] . The receptor-binding domain (RBD) of pangolin-CoV has only a one amino acid difference with that of SARS-CoV-2; the infected pangolins exhibit pathological symptoms similar to humans suffering from COVID-19, and their blood circulating antibodies can react with the spike protein of SARS-CoV-2 [35, 36] . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges abstract: The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions. url: https://www.ncbi.nlm.nih.gov/pubmed/32331255/ doi: 10.3390/pathogens9040307 id: cord-256217-fnjer0e0 author: Neri, Piergiorgio title: COVID-19 and the eye immunity: lesson learned from the past and possible new therapeutic insights date: 2020-04-20 words: 1928.0 sentences: 88.0 pages: flesch: 43.0 cache: ./cache/cord-256217-fnjer0e0.txt txt: ./txt/cord-256217-fnjer0e0.txt summary: Corona virus represents nowadays the hot topic in the scientific world due to the outbreak of a novel serotype formerly named coronavirus disease (COVID)-19 and now identified as severe acute respiratory syndrome (SARS)-COV-2 [1] . Although ECOR was used to study retinal degeneration specifically, it might represent a possible experimental model for interesting speculations on how to approach severe SARS-COV-2 pulmonary complications. Looking at the ECOR model, it gives the impression that coronavirus creates two different phases: the first is represented by the primary infection which induces the triggering of the immune system, while the second phase is likely to be an autoimmune disease where the role of the severe postviral inflammation represents a severe occurrence worth of prompt intervention. Albeit it is true that anti-IL-6 receptor monoclonal antibody has given promising results for the control of severe SARS-COV-2 pneumonia, it is interesting to notice that retinal degeneration in ECOR is associated with an evident increase in TNF-alpha, as well as soluble TNFR2, inducing an anomaly of TNF-alpha signaling [12] . abstract: nan url: https://doi.org/10.1007/s10792-020-01389-2 doi: 10.1007/s10792-020-01389-2 id: cord-302707-cap2rgf7 author: Ng, Dianna L. title: SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood date: 2020-09-17 words: 4364.0 sentences: 224.0 pages: flesch: 50.0 cache: ./cache/cord-302707-cap2rgf7.txt txt: ./txt/cord-302707-cap2rgf7.txt summary: Here, we present data validating the use of the EUA authorized Abbott Architect SARS-CoV-2 IgG test for antibody detection in two populations in March 2020, a hospitalized COVID-19 patient cohort at a tertiary care hospital in San Francisco and a cohort of blood donors from the San Francisco Bay Area. These studies demonstrate that SARS-CoV-2 seroprevalence in the San Francisco Bay Area was very low, suggesting limited circulation of the virus in the community as of early March, and that IgG and IgM titers are predictive of neutralizing activity, with high positive percent agreement. To evaluate assay sensitivity, we assembled a cohort of 38 hospitalized patients and 5 outpatients at University of California, San Francisco (UCSF) Medical Center and the San Francisco Veterans Affairs (SFVA) Health Care System, all of whom received care at adult inpatient units or clinics and were real-time polymerase chain reaction (RT-PCR) positive for SARS-CoV-2 from nasopharyngeal and/or oropharyngeal swab testing ( Fig. 1a and Supplementary Table 1 ). abstract: Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity. url: https://www.ncbi.nlm.nih.gov/pubmed/32943630/ doi: 10.1038/s41467-020-18468-8 id: cord-339762-lh8czr0a author: Ng, Dianna L. title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 date: 2016-03-31 words: 3207.0 sentences: 162.0 pages: flesch: 38.0 cache: ./cache/cord-339762-lh8czr0a.txt txt: ./txt/cord-339762-lh8czr0a.txt summary: title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a sputum specimen of a patient who died of respiratory and renal failure in Saudi Arabia in 2012. Although the pathogenesis of severe and fatal MERS-CoV infection is unknown, these postmortem findings provide critical insights, including evidence that pneumocytes are important targets, suggesting that direct cytopathic effects contribute to MERS-CoV respiratory symptoms. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans. url: https://www.sciencedirect.com/science/article/pii/S0002944015006471 doi: 10.1016/j.ajpath.2015.10.024 id: cord-291523-4dtk1kyh author: Nguyen, Thanh Thi title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 words: 5361.0 sentences: 313.0 pages: flesch: 62.0 cache: ./cache/cord-291523-4dtk1kyh.txt txt: ./txt/cord-291523-4dtk1kyh.txt summary: Outcomes of a phylogenetic analysis suggest that the virus belongs to the genus Betacoronavirus, sub-genus Sarbecovirus, which includes many bat SARS-like CoVs and SARS CoVs. Another study in [5] confirms this finding by analysing genomes obtained from three adult patients admitted to a hospital in Wuhan on December 27, 2019. With the cut-off parameter C is set equal to 0.7, the hierarchical clustering algorithm separates the reference sequences into 6 clusters in which cluster "5" comprises all examined viruses of the Sarbecovirus sub-genus, including many SARS CoVs, bat SARS-like CoVs and pangolin CoVs (Fig. 7A) . With the results obtained in Fig. 7D (and also in the experiments with the DBSCAN method presented next), we support a hypothesis that bats or pangolins are the probable origin of SARS-CoV-2. In this Appendix, we first present results of the hierarchical clustering method applied to the dataset that combines Set 1 of reference sequences (Table 1 ) with all 334 SARS-CoV-2 sequences (see Fig. 9 ). abstract: Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins. url: https://doi.org/10.1101/2020.05.12.091397 doi: 10.1101/2020.05.12.091397 id: cord-293688-g6kag5ij author: Nora, Holtmann title: Assessment of SARS-CoV-2 in human semen - a cohort study date: 2020-05-29 words: 2231.0 sentences: 146.0 pages: flesch: 57.0 cache: ./cache/cord-293688-g6kag5ij.txt txt: ./txt/cord-293688-g6kag5ij.txt summary: OBJECTIVE: To investigate the presence of viral RNA in human semen of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) recovered and positive patients and to evaluate its presence and relevance on semen parameters. SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19 positive males. SARS-CoV-2 RNA could neither be detected in semen samples from recovered nor from acute infected subjects. On another note, it is of interest, that although it was described before in the literature that viral infections have a negative impact on semen parameters like 306 volume, number of spermatozoa and motility we could not detect a negative influence of the SARS-CoV-2 infection in respect of the aforementioned sperm count parameters in recovered subjects with mild symptoms. We found no evidence of SARS-CoV-2 shedding in semen of recovered males or patients with an acute COVID-19 infection after a recovery time of 32,7 days on average. abstract: OBJECTIVE: To investigate the presence of viral RNA in human semen of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) recovered and positive patients and to evaluate its presence and relevance on semen parameters. DESIGN: Pilot cohort study SETTING: University hospital PATIENTS: 34 adult males were distributed into a) patients in convalescence (patients with confirmed SARS-CoV-2 infection in pharyngeal swab by RT-PCR and/or antibodies), b) negative control group (no antibodies) and c) patients with an acute infection (detection of SARS-CoV-2 in pharyngeal swab). INTERVENTION: Semen and a blood sample were collected from each individual. MAIN OUTCOME MEASURES: Analysis of semen quality according to the WHO standards. Detection of SARS-CoV-2 by RT-PCR in the native semen sample and after density gradient preparation. Confirmation of Immunoglobulin (Ig)-A und Ig-G antibodies in the blood. RESULTS: 18 semen samples from recovered males were obtained 8 to 54 days after absence of symptoms, 14 samples from controls and 2 samples from patients with an active COVID-19 infection. No RNA was detected by RT-PCR in the semen including semen samples from two patients with an acute COVID-19 infection. Subjects with a moderate infection showed an impairment of sperm quality. CONCLUSION: A mild COVID-19 infection is not likely to affect testis and epididymis function, whereas semen parameters did seem impaired after a moderate infection . SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19 positive males. This suggests no viral transmission during sexual contact and assisted reproductive techniques (ART), however, further data need to be obtained. url: https://doi.org/10.1016/j.fertnstert.2020.05.028 doi: 10.1016/j.fertnstert.2020.05.028 id: cord-303297-fiievwy7 author: Oberemok, Volodymyr V. title: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship date: 2020-04-30 words: 4082.0 sentences: 174.0 pages: flesch: 49.0 cache: ./cache/cord-303297-fiievwy7.txt txt: ./txt/cord-303297-fiievwy7.txt summary: In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In addition, it seems that the virus is also more likely to affect the heart than any other similar viruses, so although pneumonia is often the main cause of death, cardiologists and infectionists, for example in Russia, are seeing infected patients whose worst symptoms are not respiratory, but cardiac and many people infected with COVID-19 are dying from heart attacks, as a possible complication of SARS-CoV-2 infection. Despite the initial reports stating that most of the laboratory-confirmed infected patients (27 of 41 cases) had links to the Wuhan seafood market where different animals, including bats, snakes, birds, pangolins, and other small mammals are normally traded within the market [6] , it is now obvious that the newly identified coronavirus SARS-CoV-2 is transmitted with enormous efficacy from human to human via respiratory droplets or close contact. abstract: At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population. url: https://www.ncbi.nlm.nih.gov/pubmed/32350571/ doi: 10.1007/s00011-020-01352-y id: cord-348192-ibohbjfb author: Odih, Erkison E. title: Could Water and Sanitation Shortfalls Exacerbate SARS-CoV-2 Transmission Risks? date: 2020-06-09 words: 2676.0 sentences: 163.0 pages: flesch: 49.0 cache: ./cache/cord-348192-ibohbjfb.txt txt: ./txt/cord-348192-ibohbjfb.txt summary: Endemic and epidemic transmission of multiple feco-oral pathogens via this route continues to be documented in areas without safely managed sanitation, and, therefore, the risk of SARS-CoV-2 transmission needs to be evaluated, tracked, and forestalled in such settings. Furthermore, environmental surveillance of SARS-CoV-2 in wastewater and accumulated human waste, as well as efforts to mitigate the virus'' entry into unprotected household water sources, should be a priority part of the COVID-19 response in settings without safely managed sanitation for the duration of the pandemic. 3, 5, 6 Considerable concern has been expressed in the literature that the feco-oral transmission potential for SARS-CoV-2 places endoscopists, caregivers of diapered children who shed the virus, 7 and fecal transplant recipients 8 at high risk of contracting the infection. 20, 21 Although there are as yet no reports of transmission of SARS-CoV-2 via sewage or fecal matter in settings without safely managed sanitation, or recovery from household water, these examples demonstrate that feco-oral transmission by endemic pathogenic organisms is commonplace in these settings. abstract: SARS-CoV-2, the etiologic agent of COVID-19, is shed in stool. SARS coronaviruses have been detected in wastewater during outbreaks in China, Europe, and the United States. In this perspective, we outline the risk fecal shedding poses at locations without safely managed sanitation, as in most of Nigeria where we work. We believe that feco-oral transmission could occur if community transmission becomes high and sustained in densely populated cities without proper sanitation in Nigeria and many other African and Asian settings. In the absence of basic sanitation, or where existing sanitation is not safely managed, groundwater, which is often drawn up from wells and boreholes for drinking and household use, can become contaminated with enteric bacteria and viruses from fecal matter. Endemic and epidemic transmission of multiple feco-oral pathogens via this route continues to be documented in areas without safely managed sanitation, and, therefore, the risk of SARS-CoV-2 transmission needs to be evaluated, tracked, and forestalled in such settings. We suggest that fecal matter from treatment facilities and recovered patients should be carefully and properly disposed. Furthermore, environmental surveillance of SARS-CoV-2 in wastewater and accumulated human waste, as well as efforts to mitigate the virus’ entry into unprotected household water sources, should be a priority part of the COVID-19 response in settings without safely managed sanitation for the duration of the pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32524953/ doi: 10.4269/ajtmh.20-0462 id: cord-254916-y1rw9q11 author: Ogando, Natacha S. title: SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology date: 2020-06-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of non-structural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (remdesivir, alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that – upon passaging in Vero E6 cells – SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative furin-like cleavage site in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays. url: https://www.ncbi.nlm.nih.gov/pubmed/32568027/ doi: 10.1099/jgv.0.001453 id: cord-349682-kpg0vley author: Ojha, Probir Kumar title: Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to date: 2020-09-02 words: 7923.0 sentences: 416.0 pages: flesch: 49.0 cache: ./cache/cord-349682-kpg0vley.txt txt: ./txt/cord-349682-kpg0vley.txt summary: For example, the broad-spectrum antiviral drug Arbidol recently entered the clinical trial for the treatment of SARS-CoV-2 which may act by inhibiting virus-host cell fusion, thus preventing the viral entry into host cells against influenza virus [37] [38] [39] . Smith and Smith [22] analyzed 8000 small drug molecules and natural products (SWEETLEAD library database) employing restrained temperature replica-exchange MD simulations combining virtual screening through the ensemble docking to identify the effective drug for COVID-19 which might stop the virus by two ways: (a) disrupting S protein and ACE2 receptor interface stability; or (b) by troubling the capability of the S protein to recognize Table 2 Pharmacological safety data of selected potential drug candidates [11, 12, 14, 34, 38, 39, 43-45, 57-59, 64, 69, 70, 89] Drug Dose Drug-drug interaction Toxicity Chloroquine phosphate (Aralen) [11, 12, 14, 43, 89] This is a genetically engineered vaccine candidate with the replicationdefective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein. abstract: ABSTRACT: After the 1918 Spanish Flu pandemic caused by the H1N1 virus, the recent coronavirus disease 2019 (COVID-19) brought us to the time of serious global health catastrophe. Although no proven therapies are identified yet which can offer a definitive treatment of the COVID-19, a series of antiviral, antibacterial, antiparasitic, immunosuppressant drugs have shown clinical benefits based on repurposing theory. However, these studies are made on small number of patients, and, in majority of the cases, have been carried out as nonrandomized trials. As society is running against the time to combat the COVID-19, we present here a comprehensive review dealing with up-to-date information of therapeutics or drug regimens being utilized by physicians to treat COVID-19 patients along with in-depth discussion of mechanism of action of these drugs and their targets. Ongoing vaccine trials, monoclonal antibodies therapy and convalescent plasma treatment are also discussed. Keeping in mind that computational approaches can offer a significant insight to repurposing based drug discovery, an exhaustive discussion of computational modeling studies is performed which can assist target-specific drug discovery. GRAPHIC ABSTRACT: [Image: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/32880078/ doi: 10.1007/s11030-020-10134-x id: cord-308110-cco3aq4n author: Okamoto, Mika title: The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date: 2020-07-30 words: 2689.0 sentences: 148.0 pages: flesch: 51.0 cache: ./cache/cord-308110-cco3aq4n.txt txt: ./txt/cord-308110-cco3aq4n.txt summary: In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. Since not only the inhibition of viral replication but also the control of excessive immune activation is mandatory to save COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. abstract: Cenicriviroc (CVC) is a small-molecule chemokine receptor antagonist with highly potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity through antagonizing C-C chemokine receptor type 5 (CCR5) as a coreceptor of HIV-1. CVC also strongly antagonizes C-C chemokine receptor type 2b (CCR2b), thereby it has potent anti-inflammatory and immunomodulatory effects. CVC is currently under clinical trials in the patients for treatment of nonalcoholic steatohepatitis, in which immune cell activation and dysregulation of proinflammatory cytokines play an important role in its pathogenesis. In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Interestingly, the CCR5-specific antagonist maraviroc did not show any anti-SARS-CoV-2 activity. Although the mechanism of SARS-CoV-2 inhibition by CVC remains to be elucidated, CCR2b does not seem to be its target molecule. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. url: https://doi.org/10.1016/j.antiviral.2020.104902 doi: 10.1016/j.antiviral.2020.104902 id: cord-332948-h297ukuu author: Olotu, Fisayo A. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. date: 2020-10-16 words: 5176.0 sentences: 315.0 pages: flesch: 51.0 cache: ./cache/cord-332948-h297ukuu.txt txt: ./txt/cord-332948-h297ukuu.txt summary: authors: Olotu, Fisayo A.; Omolabi, Kehinde F.; Soliman, Mahmoud E.S. title: Leaving no stone unturned: Allosteric targeting of SARS-CoV-2 Spike protein at putative druggable sites disrupts human angiotensin-converting enzyme interactions at the receptor binding domain. 30 Identification of other functional (allosteric) sites on the prefusion S protein could present another dynamic and effective approach of preventing SARS-CoV-2 infectivity relative to its interaction with the host cell ACE2 and proteases. 53 Relatively, this study was implemented to (i) identify potential druggable sites across the S1 and S2 domains of the SARS-CoV-2 S protein other than the RBD-hACE2 interface (ii) perform high-throughput (virtual) screening of ~1500 FDA approved drugs against the most druggable site(s) (iii) investigate the binding dynamics and interaction mechanisms of the compounds and their consequential effects on the S-protein RBD-ACE2 complex. We believe this systematic study will be able to provide structural and molecular insights into possible allosteric sites on SARS-CoV-2 S protein suitable for selective targeting and structureComputational methodologies abstract: The systematic entry of SARS-CoV-2 into host cells, as mediated by its Spike (S) protein, is highly essential for pathogenicity in humans. Hence, targeting the viral entry mechanisms remains a major strategy for COVID-19 treatment. Although recent efforts have focused on the direct inhibition of S-protein receptor-binding domain (RBD) interactions with human angiotensin-converting enzyme 2 (hACE2), allosteric targeting remains an unexplored possibility. Therefore, in this study, for the first time, we employed an integrative meta-analytical approach to investigate the allosteric inhibitory mechanisms of SARS-CoV-2 S-protein and its association with hACE2. Findings revealed two druggable sites (Sites 1 and 2) located at the N-terminal domain (NTD) and S2 regions of the protein. Two high-affinity binders; ZINC3939013 (Fosaprepitant – Site 1) and ZINC27990463 (Lomitapide – Site 2) were discovered via site-directed high-throughput screening against a library of ∼1500 FDA approved drugs. Interestingly, we observed that allosteric binding of both compounds perturbed the prefusion S-protein conformations, which in turn, resulted in unprecedented hACE2 displacement from the RBD. Estimated ΔG(binds) for both compounds were highly favorable due to high-affinity interactions at the target sites. In addition, Site 1 residues; R190, H207, K206 and K187, I101, R102, I119, F192, L226, V126 and W104 were identified for their crucial involvement in the binding and stability of ZINC3939013. Likewise, energy contributions of Q957, N953, Q954, L303, Y313, Q314, L858, V952, N953, and A956 corroborated their importance to ZINC27990463 binding at the predicted Site 2. We believe these findings would pave way for the structure-based discovery of allosteric SARS-CoV-2 S-protein inhibitors for COVID-19 treatment. url: https://api.elsevier.com/content/article/pii/S2352914820306018 doi: 10.1016/j.imu.2020.100451 id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 words: 4209.0 sentences: 254.0 pages: flesch: 53.0 cache: ./cache/cord-255997-oer5lxxr.txt txt: ./txt/cord-255997-oer5lxxr.txt summary: Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . abstract: Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease. url: https://doi.org/10.1101/2020.07.10.197343 doi: 10.1101/2020.07.10.197343 id: cord-318316-9unfl966 author: Ortega, Joseph T. title: Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies date: 2020-10-23 words: 4022.0 sentences: 236.0 pages: flesch: 46.0 cache: ./cache/cord-318316-9unfl966.txt txt: ./txt/cord-318316-9unfl966.txt summary: SUMMARY: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Another early target evaluated against SARS-CoV-2 is a cellular protease related to the priming of the spike protein (S), which exposes the fusion motive and allows the release of viral RNA into the cytosol. HCQ, hydroxychloroquine; RdRp, RNA-dependent RNA polymerase; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; ORF, open reading frame. Favipiravir, another antiviral agent with broad activity against other RNA viruses by inhibiting the RdRp, halting viral replication, was evaluated against SARS-CoV-2, showing effects in vitro and in vivo [43] [44] [45] . abstract: BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease CO­VID-19 has strongly encouraged the search for antiviral compounds. Most of the evaluated drugs against SARS-CoV-2 derive from drug repurposing of Food and Drug Administration-approved molecules. These drugs have as target three major processes: (1) early stages of virus-cell interaction, (2) viral proteases, and (3) the viral RNA-dependent RNA polymerase. SUMMARY: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. KEY MESSAGES: We hypothesized that blocking of both entry mechanisms could allow a more effective antiviral effect compared to the partial results obtained with chloroquine or its derivatives alone. This approach, already used to achieve an antiviral effect higher than that offered by every single drug administered separately, has been successfully applied in several viral infections such as HIV and HCV. This review will contribute to expanding the perception of the possible therapeutic targets in SARS-CoV-2 infection and highlight the benefits of using combination therapies. url: https://doi.org/10.1159/000512141 doi: 10.1159/000512141 id: cord-286683-mettlmhz author: Ortiz-Prado, Esteban title: Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review date: 2020-05-30 words: 13299.0 sentences: 726.0 pages: flesch: 45.0 cache: ./cache/cord-286683-mettlmhz.txt txt: ./txt/cord-286683-mettlmhz.txt summary: Interestingly, the increased amounts of proinflammatory cytokines in serum associated with pulmonary inflammation and extensive lung damage described both in SARS [59] and MERS diseases [60] were also reported in the early study of 41 patients with COVID-19 in Wuhan [41] . A recently published case report of a patient with mild-to-moderate COVID-19 revealed the presence of an increased activated CD4+ T cells and CD8+ T cells, antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), and anti-SARS-CoV-2 IgM and IgG antibodies, suggesting that both cellular and humoral responses are important in containing the virus and inhibiting severe pathology [82] . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series abstract: Abstract Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20th May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19). url: https://doi.org/10.1016/j.diagmicrobio.2020.115094 doi: 10.1016/j.diagmicrobio.2020.115094 id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 words: 12332.0 sentences: 742.0 pages: flesch: 38.0 cache: ./cache/cord-262119-s6hc7fxs.txt txt: ./txt/cord-262119-s6hc7fxs.txt summary: title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms abstract: We hereby describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied to the contents of the COVID-19 Disease Map for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases. url: https://doi.org/10.1101/2020.10.26.356014 doi: 10.1101/2020.10.26.356014 id: cord-302382-eifh95zm author: Owji, Hajar title: Immunotherapeutic approaches to curtail COVID-19 date: 2020-08-21 words: 11312.0 sentences: 606.0 pages: flesch: 40.0 cache: ./cache/cord-302382-eifh95zm.txt txt: ./txt/cord-302382-eifh95zm.txt summary: Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. Nevertheless, the similarity of severe respiratory failure induced by SARS-CoV-2 to acute respiratory distress syndrome (ARDS) and the deterioration of patients'' conditions in around a week following the first symptoms implicate the role of immunity dysregulation in COVID-19 profile [6] . Subsequently, plasma transfusion was recommended as a safe and effective way for the prevention or treatment of the Ebola virus in 2014 and also several other severe viral infections, including MERS, SARS-CoV, and avian influenza A [35, 36] . CP extracted from the SARS-COV-2 survivors may be a promising approach for the protection of COVID-19 patients with antibody deficiency before the development of an effective vaccine [44] . abstract: COVID-19, the disease induced by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed an unpredictable burden on the world. Drug repurposing has been employed to rapidly find a cure; but despite great efforts, no drug or vaccine is presently available for treating or prevention of COVID-19. Apart from antivirals, immunotherapeutic strategies are suggested considering the role of the immune response as the host defense again the virus, and the fact that SARS-CoV-2 suppresses interferon induction as an immune evasion strategy. Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. The focus would be on passive immunotherapeutic interventions. Interferons might be helpful in some stages. Vaccine development has been followed with unprecedented speed. Some of these vaccines have been advanced to human clinical trials. Convalescent plasma therapy is already practiced in many countries to help save the lives of severely ill patients. Different antibodies that target various steps of SARS-CoV-2 pathogenesis or the associated immune responses are also proposed. For treating the cytokine storm induced at a late stage of the disease in some patients, immune modulation through JAK inhibitors, corticosteroids, and some other cognate classes are evaluated. Given the changing pattern of cytokine induction and immune responses throughout the COVID-19 disease course, different adapted approaches are needed to help patients. Gaining more knowledge about the detailed pathogenesis of SARS-CoV-2, its interplay with the immune system, and viral-mediated responses are crucial to identify efficient preventive and therapeutic approaches. A systemic approach seems essential in this regard. url: https://www.sciencedirect.com/science/article/pii/S1567576920324309?v=s5 doi: 10.1016/j.intimp.2020.106924 id: cord-328395-2cakgmsj author: Oxford, Alexandra E. title: Endothelial Cell Contributions to COVID-19 date: 2020-09-25 words: 6707.0 sentences: 353.0 pages: flesch: 39.0 cache: ./cache/cord-328395-2cakgmsj.txt txt: ./txt/cord-328395-2cakgmsj.txt summary: Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. This review will focus on the concept of endothelial cell infection and dysfunction as an active driver of COVID-19, which begins as a respiratory illness, with vascular pathology contributing significantly to the most negative patient outcomes. Endothelial cell infection that proceeds via ACE2 shows how SARS-CoV-2 can replicate into a wide range of cells, which may explain some of the clinical symptoms found in COVID-19 patients. Thus far, we have discussed the viral mechanisms of SARS-CoV-2 and resultant COVID-19 sequelae as they relate to endotheliitis and endothelial cell infection mediated by viral spike protein-ACE2 interaction. The successful use of anti-interleukin drugs to treat the inflammatory symptoms seen in severe COVID-19 would have marked effects on endothelial pathology as these cells are highly responsive to cytokine signaling [59] . abstract: Understanding of the clinical, histological and molecular features of the novel coronavirus 2019 (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has remained elusive. Coronavirus disease 2019 (COVID-19) caused by this virus has unusual clinical presentation with regard to other related coronaviruses. Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. Likewise, mounting evidence associates vascular and endothelial cell dysfunction with increased mortality. This review focuses on understanding how endothelial cell pathology is caused by SARS-CoV-2 at the molecular and cellular levels and how these events relate to COVID-19. A detailed examination of current knowledge regarding canonical inflammatory reaction pathways as well as alteration of endothelial cell-derived exosomes and transdifferentiation by SARS-CoV-2 is included in this assessment. Additionally, given an understanding of endothelial contributions to COVID-19, potential therapeutic aims are discussed, particularly as would affect endothelial function and pathology. url: https://doi.org/10.3390/pathogens9100785 doi: 10.3390/pathogens9100785 id: cord-278370-fuu20ae7 author: Palao, M. title: Multiple Sclerosis following SARS-CoV-2 infection date: 2020-07-07 words: 1544.0 sentences: 93.0 pages: flesch: 44.0 cache: ./cache/cord-278370-fuu20ae7.txt txt: ./txt/cord-278370-fuu20ae7.txt summary: However, available information about demyelinating complications of the central nervous system (CNS) is limited with only one report of acute disseminated encephalomyelitis (ADEM) in a severe COVID-19 patient being published to date 5 and a single case of meningo-encephalitis 6 , the latter with the presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) confirmed by PCR. As viral infections have been linked to the development of demyelinating diseases 7 it would be interesting to know if this relationship also exists in the case of SARS-CoV-2. We present a case of first presentation of demyelinating disease in the form of optic neuritis following SARS-CoV-2 infection. In our case, the patient presented symptoms attributed to COVID-19 infection (anosmia and dysgeusia) prior to the visual manifestations. In this case, SARS-CoV-2 may have acted as a precipitating factor rather than multiple sclerosis being a direct consequence of the infection. abstract: SARS-CoV-2 infection can produce neurological features. The most common are headache, anosmia and dysgeusia but patients may also develop other central nervous system (CNS) injuries. We present a patient affected by Covid-19 who initially consulted for decreased visual acuity. The MRI showed inflammation in the right optic nerve and demyelinating lesions in the CNS. We speculate that an immune mechanism induced by SARS-CoV-2, which can activate lymphocytes and an inflammatory response, plays a role in the clinical onset of the disease. This pathogen may be associated with either the triggering or the exacerbation of inflammatory/demyelinating disease. url: https://api.elsevier.com/content/article/pii/S2211034820304521 doi: 10.1016/j.msard.2020.102377 id: cord-301730-flv5lnv8 author: Pandey, Anamika title: Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak date: 2020-10-15 words: 7101.0 sentences: 346.0 pages: flesch: 50.0 cache: ./cache/cord-301730-flv5lnv8.txt txt: ./txt/cord-301730-flv5lnv8.txt summary: Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. Medicinal plant extracts have been reported to impede the replication of several viruses including human immunodeficiency virus (HIV), hepatitis B virus (HBV), poxvirus, severe acute respiratory syndrome (SARS) virus, and herpes simplex virus type 2 (HSV-2) (Vermani and Garg, 2002; Kotwal et al., 2005; Huang et al., 2006) . Different researchers are investigating diverse plant forms based on ethnopharmacological data to find effective anti-CoV drugs with novel action mechanisms especially targeting viral replication. Moreover, creating an effective phyto-anti-COVID drug during this pandemic may provide an idea on the duration and the strategy required for the development of potent plant-based therapeutics in case of such random viral outbreaks (Figure 1) . abstract: The sudden emergence of COVID-19 caused by a novel coronavirus (nCoV) led the entire world to search for relevant solutions to fight the pandemic. Although continuous trials are being conducted to develop precise vaccines and therapeutic antibodies, a potential remedy is yet to be developed. Plants have largely contributed to the treatment of several human diseases and different phytoconstituents have been previously described to impede the replication of numerous viruses. Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. In this article, we discuss varying perspectives on why phyto-anti-viral drug clinical trials were not successful in the case of COVID-19. The issue has been discussed in light of the usage of plant-based therapeutics in previous coronavirus outbreaks. Through this article, we aim to identify the disadvantages in this research area and suggest some measures to ensure that phytoconstituents can efficiently contribute to future random viral outbreaks. It is emphasized that if used strategically phyto-inhibitors with pre-established clinical data for other diseases can save the time required for long clinical trials. The scientific community should competently tap into phytoconstituents and take their research up to the final stage of clinical trials so that potential phyto-anti-COVID drugs can be developed. url: https://www.ncbi.nlm.nih.gov/pubmed/33178237/ doi: 10.3389/fpls.2020.568890 id: cord-318164-6rqi17oz author: Paoli, D. title: Sperm cryopreservation during the SARS-CoV-2 pandemic date: 2020-10-10 words: 3258.0 sentences: 177.0 pages: flesch: 48.0 cache: ./cache/cord-318164-6rqi17oz.txt txt: ./txt/cord-318164-6rqi17oz.txt summary: This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation. This study thus aimed to evaluate the safety of sperm cryopreservation of cancer patients referred to our sperm bank after the onset of the pandemic in Italy through the assessment of the risk of SARS-CoV-2 exposure and, in selected volunteers, viral RNA testing of semen samples. This was further confirmed by testing seminal fluid samples from 10 asymptomatic cancer patients for SARS-CoV-2 RNA. abstract: PURPOSE: Sperm cryopreservation is fundamental in the management of patients undergoing gonadotoxic treatments. Concerns have risen in relation to SARS-CoV-2 and its potential for testicular involvement, since SARS-CoV-2-positive cryopreserved samples may have unknown effects on fertilization and embryo safety. This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. METHODS: We recruited 10 cancer patients (mean age 30.5 ± 9.6 years) referred to our Sperm Bank during the Italian lockdown (from March 11th to May 4th 2020) who had not undergone a nasopharyngeal swab for SARS-CoV-2 testing. Patients were administered a questionnaire on their exposure to COVID-19, and semen samples were taken. Before cryopreservation, SARS-CoV-2 RNA was extracted from a 150 µl aliquot of seminal fluid in toto using QIAamp viral RNA kit (Qiagen) and amplified by a real time RT PCR system (RealStar SARS-CoV2 RT PCR, Altona Diagnostics) targeting the E and S genes. RESULTS: The questionnaire and medical interview revealed that all patients were asymptomatic and had had no previous contact with COVID-19 infected patients. All semen samples were negative for SARS-CoV-2 RNA. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation. url: https://doi.org/10.1007/s40618-020-01438-8 doi: 10.1007/s40618-020-01438-8 id: cord-339859-anatn295 author: Paret, Michal title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress date: 2020-04-17 words: 1286.0 sentences: 105.0 pages: flesch: 59.0 cache: ./cache/cord-339859-anatn295.txt txt: ./txt/cord-339859-anatn295.txt summary: title: SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress We report two cases of SARS-CoV-2 infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time RT-PCR-based testing for SARS-CoV-2 for febrile infants in an outbreak setting. [2] [3] [4] Even in the setting of asymptomatic or mildly symptomatic infection, children may represent a source of SARS-CoV-2 spread in community or hospital settings, so understanding the spectrum of COVID-19 illness in infants, particularly regarding conditions that result in hospitalization, is crucial to establishment of effective infection control interventions. Vital signs and pertinent laboratory findings appear in the A real-time RT-PCR assay performed at the New York State Department of Health detected SARS-CoV-2 RNA in the patient''s NP sample. abstract: We report two cases of SARS-CoV-2 infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time RT-PCR-based testing for SARS-CoV-2 for febrile infants in an outbreak setting. url: https://doi.org/10.1093/cid/ciaa452 doi: 10.1093/cid/ciaa452 id: cord-278522-e4qa19o6 author: Park, Se Yoon title: Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs date: 2020-06-19 words: 1605.0 sentences: 106.0 pages: flesch: 56.0 cache: ./cache/cord-278522-e4qa19o6.txt txt: ./txt/cord-278522-e4qa19o6.txt summary: There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs Se Yoon Park 1 , Soon Gyu Yun 2 , Jeong Won Shin 2 , Bo Young Lee 3 , Hyo-Ju Son 1 , Seungjae Lee 1 , Eunjung Lee 1 , and Tae Hyong Kim 1 Since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than three million people in 211 countries. Few studies have investigated the duration of SARS-CoV-2 detection during the patients'' recovery phase after resolution of COVID-19-associated symptoms/signs. SARS-CoV-2 shedding continued for about 4 weeks after resolution of COVID-19-associated symptoms/signs, with the longest period being 48 days. In conclusion, we found that SARS-CoV-2 virus shedding can persist for more than three weeks after resolution of COVID-19-associated symptoms/signs. abstract: There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. We determined duration of SARS-CoV-2 virus shedding in symptomatic patients after remission of symptoms. We investigated the duration of SARS-CoV-2 RNA detection using real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or sputum or saliva. Six patients were included in the final analysis. The median (range) duration of SARS-CoV-2 viral detection after hospitalization was 34 days (22 to 67). After resolution of symptoms/signs, SARS-CoV-2 RNA was detected for median (range) of 26 days (9 to 48). Among the six patients, one had persistent detection of SARS-CoV-2 RNA until day 67 of hospitalization, which was 30 days after symptom resolution. This case represents the longest duration of SARS-CoV-2 detection, and highlights the need for long-term follow up of COVID-19 patients despite resolution of symptoms to confirm SARS-CoV-2 clearance. url: https://doi.org/10.3904/kjim.2020.203 doi: 10.3904/kjim.2020.203 id: cord-274396-l611eisi author: Park, Su-Jin title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets date: 2020-05-22 words: 4355.0 sentences: 208.0 pages: flesch: 46.0 cache: ./cache/cord-274396-l611eisi.txt txt: ./txt/cord-274396-l611eisi.txt summary: While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. In order to determine the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine (HCQ) sulfate, or emtricitabine-tenofovir for treatment of SARS-CoV-2 infection, SARS-CoV-2 antibody-free ferrets (10/group) were inoculated with 10 5.8 50% tissue culture infective doses (TCID 50 )/ml of an NMC-nCoV02 strain through the intranasal (i.n.) route ( Fig. 1 ). Therefore, although clinical symptoms were attenuated in ferret groups treated with antiviral candidates, we also evaluated virus titers in respiratory and gastrointestinal tracts using nasal washes and stool samples, respectively, from SARS-CoV-2-infected ferrets. abstract: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32444382/ doi: 10.1128/mbio.01114-20 id: cord-268540-wrjzr3ws author: Park, You Jeong title: Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics date: 2020-08-13 words: 16363.0 sentences: 868.0 pages: flesch: 45.0 cache: ./cache/cord-268540-wrjzr3ws.txt txt: ./txt/cord-268540-wrjzr3ws.txt summary: A potential target for drug development for COVID-19 also involves inhibition of ACE2, the host cell receptor for the S protein of SARS-CoV-2 that is primed by TMPRSS2 protease and may prevent the entry of the virus. As previously described, the intermolecular interaction between the viral SP and human ACE2 Phase II CAStem cells will be intravenously injected into patients with or without acute respiratory distress syndrome (ARDS) induced by COVID-19. Phase II Patients with acute respiratory distress syndrome caused by COVID-19 will be treated with intravenous UC-MSCs at a dose 1 million xKg. Patient improvement will be evaluated over three weeks, along with the assessment of the immune profile, investigating the stem cells'' effect on the cytokine storm. The similarities in systemic multi-organ complications between H7N9 and Sars-Cov-2 infections, along with direct evidence of the benefits of MSCs transplantation for COVID-19, further supports the potential of stem cells as an effective treatment [138] . abstract: The human population is in the midst of battling a rapidly-spreading virus— Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today’s pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. [Figure: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/32789802/ doi: 10.1007/s12015-020-10026-5 id: cord-339665-nwwutduy author: Patel, Ami title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 words: 5258.0 sentences: 286.0 pages: flesch: 52.0 cache: ./cache/cord-339665-nwwutduy.txt txt: ./txt/cord-339665-nwwutduy.txt summary: Prior work with the related coronaviruses, SARS-CoV and MERS-CoV, delineated that the Spike protein of these viruses was an important target for development of neutralizing antibodies, and in animal viral challenges vaccine targeted immunity (reviewed in (Du et al., 2009; Roper and Rehm, 2009; Thanh Le et al., 2020) (Liu et al., 2018; Muthumani et al., 2015; van Doremalen et al., 2020a) . These memory titers were comparable to those observed in other reported protection studies in macaques performed at the acute phase of the vaccine-induced immune response (Gao et al., 2020; van Doremalen et al., 2020b; Yu et al., 2020) and those reported in the sera of convalescent patients (Ni et al., 2020; Robbiani et al., 2020) . Our study and other published reports show that DNA vaccination with candidates targeting the full-length SARS-CoV-2 spike protein likely increase the availability of T cell immunodominant epitopes leading to a broader and more potent immune response, compared to partial domains and truncated immunogens. abstract: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease. url: https://doi.org/10.1101/2020.07.28.225649 doi: 10.1101/2020.07.28.225649 id: cord-271781-cfv0ta10 author: Patel, Kishan P. title: Transmission of SARS-CoV-2: an update of current literature date: 2020-07-07 words: 4469.0 sentences: 232.0 pages: flesch: 47.0 cache: ./cache/cord-271781-cfv0ta10.txt txt: ./txt/cord-271781-cfv0ta10.txt summary: To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Additionally, studies have noted that its fecal-oral transmission potential may lie in the fact that prolonged viral shedding can occur in fecal matter-one case reported an asymptomatic COVID-19 patient experiencing viral detection in the stool for up to 42 days, while nasopharyngeal sampling was negative [31] . To oppose, in a retrospective review of nine COVID-19 pregnant mothers who underwent cesarean section, six patients had samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples tested for SARS-CoV-2, and all were negative [43] . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2. url: https://doi.org/10.1007/s10096-020-03961-1 doi: 10.1007/s10096-020-03961-1 id: cord-342383-ckswlo9o author: Pawlowski, C. title: Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations date: 2020-07-28 words: 5479.0 sentences: 273.0 pages: flesch: 51.0 cache: ./cache/cord-342383-ckswlo9o.txt txt: ./txt/cord-342383-ckswlo9o.txt summary: Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI: (0.32, 0.64), p-value: 6.9e-05). Given this study population, we assess the rates of SARS-CoV-2 infection among individuals who did and did not receive one of 18 vaccines in the past 1, 2, and 5 years relative to the date of PCR testing. In Figure 6 , we present the results from the tipping point analysis on the statistically significant associations between vaccination and reduced rates of SARS-CoV-2 infection in the overall study population. For example, for the polio vaccine at the 1 year time horizon, an unobserved confounder with a relative risk of 2.78 which is prevalent in 17.8% of the vaccinated cohort and 0% of the unvaccinated cohort could explain the differences in SARS-CoV-2 infection rates that we observe in the data. abstract: Multiple clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Hemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), varicella, pneumococcal conjugate (PCV13), geriatric flu, and hepatitis A / hepatitis B (HepA-HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI: (0.32, 0.64), p-value: 6.9e-05). These findings suggest that additional pre-clinical and clinical studies are warranted to assess the protective effects of existing non-COVID-19 vaccines and explore underlying immunologic mechanisms. We note that the findings in this study are preliminary and are subject to change as more data becomes available and as further analysis is conducted. url: https://doi.org/10.1101/2020.07.27.20161976 doi: 10.1101/2020.07.27.20161976 id: cord-262266-m0fjt483 author: Peddu, Vikas title: Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization date: 2020-05-07 words: 1847.0 sentences: 110.0 pages: flesch: 53.0 cache: ./cache/cord-262266-m0fjt483.txt txt: ./txt/cord-262266-m0fjt483.txt summary: METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Eight unique patient samples consisting of six positive and two negative cases of suspected SARS-CoV-2 were sequenced using RNA extracted for a qRT-PCR diagnostic assay. Despite our reference database not containing any SARS-CoV-2 genomes, the six samples that were positive for SARS-CoV-2 by qRT-PCR had reads classified to Table 2) . Phylogenetic analysis revealed that the six SARS-CoV-2 sequences found cluster within two clades representing the Washington state and European outbreaks. abstract: BACKGROUND: More than two months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 hours our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients’ respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics. url: https://doi.org/10.1093/clinchem/hvaa106 doi: 10.1093/clinchem/hvaa106 id: cord-311847-2czqs84q author: Pennisi, Manuela title: SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms date: 2020-07-31 words: 9002.0 sentences: 433.0 pages: flesch: 40.0 cache: ./cache/cord-311847-2czqs84q.txt txt: ./txt/cord-311847-2czqs84q.txt summary: Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). Although there are limitations in the epidemiological studies carried on COVID-19, as well as limited case records for determining the actual incidence of these complications, some patients reported neurological symptoms, but clinical findings and pathogenic features have not yet systematically addressed. The aims of this review are i) to summarize the available information on the relationship between CoVs and the nervous system, ii) to identify the potential targets and routes of entry of SARS-CoV-2 into the nervous system, and iii) to describe the range of the neurological features reported to date in patients with COVID-19 and the proposed pathogenic mechanisms. Indeed, no axonal transport of SARS-CoV-2 to the brain has been demonstrated in the hamster model during the first two weeks after infection [89] , and no viral accumulation or persistence has been reported in cerebral olfactory regions of autopsy material from patients with COVID-19 [90] . abstract: Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction. url: https://www.ncbi.nlm.nih.gov/pubmed/32751841/ doi: 10.3390/ijms21155475 id: cord-293274-ysr1l557 author: Perisé-Barrios, Ana Judith title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 words: 4140.0 sentences: 267.0 pages: flesch: 54.0 cache: ./cache/cord-293274-ysr1l557.txt txt: ./txt/cord-293274-ysr1l557.txt summary: Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. abstract: COVID-19 is a zoonotic disease originated by SARS-CoV-2. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Therefore it is necessary to describe the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19. The potential for companion animals contributing to the continued human-to-human disease, infectivity, and community spread is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound study, and computed tomography. Nasopharyngeal and rectal swab were analyzed to detect canine pathogens, including SARS-CoV-2. Twenty healthy dogs living in SARS-CoV-2 positive households were included. Immunoglobulin detection by different immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial pattern, with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. Forty dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Moreover, dogs living in COVID-19 positive households could have been more exposed to be infected during outbreaks. url: https://doi.org/10.1101/2020.09.22.308023 doi: 10.1101/2020.09.22.308023 id: cord-150183-zzzyewjb author: Phillips, J. C. title: Synchronized Attachment and the Darwinian Evolution of Coronaviruses CoV-1 and CoV-2 date: 2020-08-27 words: 2483.0 sentences: 154.0 pages: flesch: 55.0 cache: ./cache/cord-150183-zzzyewjb.txt txt: ./txt/cord-150183-zzzyewjb.txt summary: These are (CoV-1 site numbering from Uniprot P59594): 546Gln to Leu; 556 and 561Ser to Ala; and 568Ser to Leu. The differences associated with each of these mutations are hydropathically large (~50-100 in the MZ scale [4] ; all 20 amino acids span a range from most hydrophilic to most hydrophobic of 170). The central hydrophilic level set, absent from CoV-1 and present in CoV-2, is our main result ( There is an excellent review of the principles of self-organized criticality in living matter [3] . Some readers may be interested in the connections between hydropathic scaling theory of proteins and the more general synchronization of complex networks. Now that we are in the genomic age, with a very large sequence data base available for many proteins and many species, the discovery of these 20 fractals [5, 13] opens a new biophysics field of accurate thermodynamic analysis of small but medically important evolutionary differences. abstract: CoV2019 has evolved to be much more dangerous than CoV2003. Experiments suggest that structural rearrangements dramatically enhance CoV2019 activity. We identify a new first stage of infection which precedes structural rearrangements by using biomolecular evolutionary theory to identify sequence differences enhancing viral attachment rates. We find a small cluster of mutations which show that CoV-2 has a new feature that promotes much stronger viral attachment and enhances contagiousness. The extremely dangerous dynamics of human coronavirus infection is a dramatic example of evolutionary approach of self-organized networks to criticality. It may favor a very successful vaccine. The identified mutations can be used to test the present theory experimentally. url: https://arxiv.org/pdf/2008.12168v2.pdf doi: nan id: cord-351169-y91fdf66 author: Phillips, Lia title: Successful management of SARS-CoV-2 acute respiratory distress syndrome and newly diagnosed acute lymphoblastic leukemia date: 2020-09-14 words: 1732.0 sentences: 105.0 pages: flesch: 37.0 cache: ./cache/cord-351169-y91fdf66.txt txt: ./txt/cord-351169-y91fdf66.txt summary: Corticosteroid can be given safely to patients with SARS-CoV-2 presenting with acute respiratory distress syndrome and ALL. Although recommendations are emerging for the general management of oncology patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1,2 there is little experience in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Providers may have concern about initiating multiagent chemotherapy in patients with SARS-CoV-2, particularly corticosteroids, which are an essential part of induction regimens, but raise the theoretical possibility of delayed viral clearance. We describe our experience of successfully initiating therapy for an adolescent diagnosed with ALL, while managing severe SARS-CoV-2 infection marked by respiratory failure, systemic inflammation, and autoimmune hemolytic anemia (AIHA). 1, 2 In this case, intensive remission induction chemotherapy was initially delayed due to concern for potential worsening of SARS-CoV-2 disease by exacerbating the patient''s already immunocompromised state in the setting of ALL. abstract: Standard chemotherapy can still be used for new diagnosis of acute lymphoblastic leukemia in patients with SARS-CoV-2. Corticosteroid can be given safely to patients with SARS-CoV-2 presenting with acute respiratory distress syndrome and ALL. url: https://doi.org/10.1182/bloodadvances.2020002745 doi: 10.1182/bloodadvances.2020002745 id: cord-308945-i2agpvhk author: Phipps, William S title: SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity date: 2020-07-15 words: 3167.0 sentences: 174.0 pages: flesch: 50.0 cache: ./cache/cord-308945-i2agpvhk.txt txt: ./txt/cord-308945-i2agpvhk.txt summary: METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)–based respiratory viral panel. Long et al 8 have described a variable antiviral IgM and IgG immune response to SARS-CoV-2 infection in a Chinese population in which seroconversion in a group of 285 patients from 3 hospitals showed IgG positivity for all cases beyond 17 to 19 days. The goals of this study were to ascertain key performance metrics of analytical specificity and cross-reactivity for a SARS-CoV-2 IgG serologic assay, perform a detailed cross-sectional and serial assessment of IgG and IgM antibody responses in suspected COVID-19 patients, and determine their relation to disease severity. SARS-CoV-2 IgG antibody results agreed with the PCR-negative samples for 96 of 97 (99%) of cases, including 55 instances of patients with new or acute-on-chronic symptoms suspicious for COVID-19 and with known time of onset. abstract: OBJECTIVES: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)–based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method. RESULTS: All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. CONCLUSIONS: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population. url: https://www.ncbi.nlm.nih.gov/pubmed/32666092/ doi: 10.1093/ajcp/aqaa123 id: cord-261718-zqoggwnk author: Pietschmann, Jan title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 words: 1188.0 sentences: 76.0 pages: flesch: 45.0 cache: ./cache/cord-261718-zqoggwnk.txt txt: ./txt/cord-261718-zqoggwnk.txt summary: Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. After addition of 176 biotinylated GaR and subsequent labelling with streptavidin-AP, the ELISA plate was read out at 177 405 nm and obtained measuring values were used to generate calibration curves for SARS-CoV-2 178 specific antibody concentrations in PBS (Fig 1, black curve) and in human serum samples (Fig 1, red 179 curve). Same calibration measurements employing dilutions of SARS-CoV-2 specific antibody were 211 done with our PoC MInD-based setup (Fig 2 and 3) . Comparable to laboratory-based ELISA, the same 212 dilutions of SARS-CoV-2 spike protein peptide specific antibody in PBS-buffer (Fig 3, black abstract: SARS-CoV-2 causes ongoing infections worldwide, and identifying people with immunity is becoming increasingly important. Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. SARS-CoV-2 peptide reactive antibodies, spiked at different concentrations into PBS and human serum, were rinsed through immunofiltration columns. Specific antibodies were retained within the IFC and labelled with an isotype specific biotinylated antibody. Streptavidin-functionalized magnetic nanoparticles were applied to label the secondary antibodies. Enriched magnetic nanoparticles were then detected by means of frequency magnetic mixing detection technology, using a portable magnetic read-out device. Measuring signals corresponded to the amount of SARS-CoV-2 specific antibodies in the sample. Our preliminary magnetic immuno-detection setup resulted in a higher sensitivity and broader detection range and was four times faster than ELISA. Further optimizations could reduce assay times to that of a typical lateral flow assay, enabling a fast and easy approach, well suited for point-of-care measurements without expensive lab equipment. url: https://doi.org/10.1101/2020.06.02.131102 doi: 10.1101/2020.06.02.131102 id: cord-262958-tmp6yxlv author: Pinto, Dora title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody date: 2020-04-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32511354/ doi: 10.1101/2020.04.07.023903 id: cord-193133-puqcbf8t author: Piplani, Sakshi title: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus date: 2020-05-13 words: 3815.0 sentences: 215.0 pages: flesch: 51.0 cache: ./cache/cord-193133-puqcbf8t.txt txt: ./txt/cord-193133-puqcbf8t.txt summary: The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Here we show how computational chemistry methods from structure-based drug design can be used to determine the relative binding affinities of the SARS-CoV-2 spike protein for its receptor, angiotensin converting enzyme (ACE)-2, a critical initiating event for SARS-CoV-2 infection, across multiple common and exotic animal species. 31, 32 Molecular docking was performed on the homology modelled SARS-CoV-2 spike protein with human and animal ACE2 proteins. The molecular dynamics simulation of complexes of SARS-CoV-2 spike protein and ACE2 receptors of various species were performed for 100ns. abstract: The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. In silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used a structural homology modeling approach to characterize the SARSCoV2 spike protein and predict its binding strength to the human ACE2 receptor. We then explored the possible transmission path by which SARSCoV2 might have crossed to humans by constructing models of ACE2 receptors of relevant species, and calculating the binding energy of SARSCoV2 spike protein to each. Notably, SARSCoV2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARSCoV2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin, which is most likely explained by a process of convergent evolution. Binding of SARSCoV2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for human ACE2, and is consistent with only occasional observations of infections of these domestic animals. Overall, the data indicates that SARSCoV2 is uniquely adapted to infect humans, raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere. url: https://arxiv.org/pdf/2005.06199v1.pdf doi: nan id: cord-346960-3empldlo author: Plebani, M. title: Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity date: 2020-08-04 words: 2282.0 sentences: 134.0 pages: flesch: 46.0 cache: ./cache/cord-346960-3empldlo.txt txt: ./txt/cord-346960-3empldlo.txt summary: In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. 54 SARS-CoV-2 negative subjects (33 healthcare workers, 21 autoimmune patients, 8 pregnant women) were included in the study ( Moreover, Liaison SARS-CoV-2 S1/S2 IgG (Diasorin, Sallugia-VC, Italy), ENZY-Well SARS-CoV-2 IgA and IgM were evaluated for the correlation with the neutralization results. . To provide insight on neutralization activity compared with immunoassays results, PRNT assay was performed on 52 samples from SARS-CoV-2 positive subjects. abstract: Background. Reliable high-throughput serological assays for SARS-CoV-2 antibodies (Abs) are urgently needed for the effective containment of the COVID-19 pandemic, as it is of crucial importance to understand the strength and duration of immunity after infection, and to make informed decisions concerning the activation or discontinuation of physical distancing restrictions. Methods. In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). Findings. Precision results ranged from 0.9% to 11.8% for all assays. Elecsys anti-SARS-CoV-2 demonstrated linearity of results at concentrations within the cut-off value. Overall, sensitivity ranged from 78.5 to 87.8%, and specificity, from 97.6 to 100%. On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. The strongest PRNT50 correlation with antibody levels was obtained with ENZY-Well SARS-CoV-2 IgG (rho = 0.541, p < 0.001). Interpretation. The results confirmed that all immunoassays had an excellent specificity, whereas sensitivity varied across immunoassays, depending strongly on the time interval between symptoms onset and sample collection. Further studies should be conducted to achieve a stronger correlation between antibody measurement and PRNT50 in order to obtain useful information for providing effective passive antibody therapy, and developing a vaccine against the SARS-CoV-2 virus. url: http://medrxiv.org/cgi/content/short/2020.08.01.20166546v1?rss=1 doi: 10.1101/2020.08.01.20166546 id: cord-298669-g2up0cfi author: Pollock, David D title: Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2 date: 2020-07-13 words: 3261.0 sentences: 158.0 pages: flesch: 52.0 cache: ./cache/cord-298669-g2up0cfi.txt txt: ./txt/cord-298669-g2up0cfi.txt summary: Nevertheless, the evolutionary reasons for low GC content are still debated in even exceptionally well-studied systems with unquestioned animal origins (2020) points out, the mammalian zinc finger antiviral protein (ZAP) binds to CpG dinucleotides in viral RNA genomes and inhibits viral replication and mediates viral degradation (Ficarelli et al., 2020; Ficarelli et al., 2019; Meagher et al., 2019; Takata et al., 2017) . Despite this, Xia (2020) speculated that low viral genomic CpG levels in SARS-CoV-2 required evolutionary time in a previous host species and tissue that more actively selected for CpG depletion than do bats. In addition to being unsupported by positive evidence, Xia''s (2020) hypothesis for dogs as intermediate hosts of ancestral viruses giving rise to SARS-CoV-2 requires an unlikely history of cross-species viral transmission (see Fig. 2 for potential hypotheses) for which there is no evidence. abstract: Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia’s inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited. url: https://www.ncbi.nlm.nih.gov/pubmed/32658964/ doi: 10.1093/molbev/msaa178 id: cord-310017-c8rd714a author: Popa, Alexandra title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 words: 5572.0 sentences: 330.0 pages: flesch: 49.0 cache: ./cache/cord-310017-c8rd714a.txt txt: ./txt/cord-310017-c8rd714a.txt summary: Moreover, we combined our deep viral genome sequencing data with epidemiologically identified chains of transmissions and family clusters together with biomathematical analyses to study genetic bottlenecks and the dynamics of genome evolution of SARS-CoV-2. We assembled SARS-CoV-2 genome sequences, constructed phylogenies and identified low 15 frequency mutations based on high-quality sequencing results with >5 million reads per sample and >80% of mapped viral reads (Fig. S2A-B) . Our pipeline was validated by experimental controls involving sample titration and technical sample replicates ( Fig. S2CTo investigate the link between local outbreaks in Austria and the global pandemic, we 20 performed phylogenetic analysis of 305 SARS-CoV-2 genomes from the Austrian cases (>96% genome coverage, >80% aligned viral reads) and 7,695 global genomes from the GISAID database (Fig. 1B, Table S1 ). 7 Dynamics of low frequency and fixed mutations in clusters Next, we sought to gain insights into the fundamental processes of SARS-CoV-2 infection by integrative analysis of viral genomes. abstract: Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, a country that played a major role for virus transmission across Europe and beyond. Capitalizing on a national epidemiological surveillance system, we performed deep whole-genome sequencing of virus isolates from 576 samples to cover major Austrian SARS-CoV-2 clusters. Our data chart a map of early viral spreading in Europe, including the path from low-frequency mutations to fixation. Detailed epidemiological surveys enabled us to calculate the effective SARS-CoV-2 population bottlenecks during transmission and unveil time-resolved intra-patient viral quasispecies dynamics. This study demonstrates the power of integrating deep viral genome sequencing and epidemiological data to better understand how SARS-CoV-2 spreads through populations. Graphical Abstract url: https://doi.org/10.1101/2020.07.15.204339 doi: 10.1101/2020.07.15.204339 id: cord-258914-g6pv8zz9 author: Proud, Pamela C. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 words: 1191.0 sentences: 90.0 pages: flesch: 51.0 cache: ./cache/cord-258914-g6pv8zz9.txt txt: ./txt/cord-258914-g6pv8zz9.txt summary: title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. The TLRs are key microbe-recognition receptors with a crucial role in 97 activation of host defence and protection from infections and therefore attractive drug 98 targets against infectious diseases [12] [13] [14] To determine whether TLR2/6 agonists are also active against SARS-CoV-2, we used In life samples were taken at days 1, 3, 5, 7, 10 and 12, with scheduled culls at days 137 3 (n=6) and end of study days 12-14 (n=18) (Fig 1A) . abstract: Respiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. url: https://doi.org/10.1101/2020.09.25.309914 doi: 10.1101/2020.09.25.309914 id: cord-288731-x2cwyvb7 author: Puenpa, Jiratchaya title: Molecular epidemiology of the first wave of severe acute respiratory syndrome coronavirus 2 infection in Thailand in 2020 date: 2020-10-06 words: 4207.0 sentences: 275.0 pages: flesch: 57.0 cache: ./cache/cord-288731-x2cwyvb7.txt txt: ./txt/cord-288731-x2cwyvb7.txt summary: In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. In Thailand the Ministry of Public Health reported the first laboratory-confirmed case of SARS-CoV-2 in a 61-year-old Chinese traveller who had arrived from Wuhan on 12 January 2020. Based on the genome sequences available in GIASID, nucleotide variation in four regions of the SARS-CoV-2 genome was used to conduct viral tracking and identify sites of origin of outbreaks in Thailand. One sample in the current study collected in January 2020 was closely related to the SARS-CoV-2 strain circulating in China at that time identified as type L. A new cohort of imported cases identified in May 2020 included a group of migrant workers in the southern part of Thailand 24 with type G2 SARS-CoV-2. abstract: The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major global concern. Several SARS-CoV-2 gene mutations have been reported. In the current study associations between SARS-CoV-2 gene variation and exposure history during the first wave of the outbreak in Thailand between January and May 2020 were investigated. Forty samples were collected at different time points during the outbreak, and parts of the SARS-CoV-2 genome sequence were used to assess genomic variation patterns. The phylogenetics of the 40 samples were clustered into L, GH, GR, O and T types. T types were predominant in Bangkok during the first local outbreak centered at a boxing stadium and entertainment venues in March 2020. Imported cases were infected with various types, including L, GH, GR and O. In southern Thailand introductions of different genotypes were identified at different times. No clinical parameters were significantly associated with differences in genotype. The results indicated local transmission (type T, Spike protein (A829T)) and imported cases (types L, GH, GR and O) during the first wave in Thailand. Genetic and epidemiological data may contribute to national policy formulation, transmission tracking and the implementation of measures to control viral spread. url: https://www.ncbi.nlm.nih.gov/pubmed/33024144/ doi: 10.1038/s41598-020-73554-7 id: cord-335155-x9az3twa author: Qi, Zhen title: Phylogeny of SARS-CoV as inferred from complete genome comparison date: 2003 words: 1616.0 sentences: 97.0 pages: flesch: 59.0 cache: ./cache/cord-335155-x9az3twa.txt txt: ./txt/cord-335155-x9az3twa.txt summary: SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. To date, genomes from 12 SARS-CoV isolates and 12 previously identified coronaviruses have been completely sequenced. The unrooted phylogenetic tree was constructed for genomes from 12 SARS-CoV isolates and that from 12 previously identified coronviruses (Fig. 1) . Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJOI) abstract: SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique. Meanwhile, the three groups of coronaviruses depart from each other clearly in our tree that is consistent with the results of prevenient papers. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. The topology map also shows that the 12 SARS-CoV isolates may be divided into two groups determined by the association with the SARS-CoV from the Hotel M in Hong Kong that may give some information about the infectious relationship of the SARS. url: https://doi.org/10.1007/bf03183930 doi: 10.1007/bf03183930 id: cord-343827-jo61t3m0 author: Qian, Qun title: Direct evidence of active SARS-CoV-2 replication in the intestine date: 2020-07-08 words: 1314.0 sentences: 98.0 pages: flesch: 53.0 cache: ./cache/cord-343827-jo61t3m0.txt txt: ./txt/cord-343827-jo61t3m0.txt summary: We investigated the presence of virions and pathological changes in surgical rectal tissues of a clinically confirmed COVID-19 patient with rectal adenocarcinoma. RNA of SARS-CoV-2 was detected in surgically resected rectal specimens, but not in samples collected on 37 day after discharge. Notably, coincidence with rectal tissues of surgical specimens tested nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Notably, fecal samples remained positive for SARS-CoV-2 RNA nearly 5 weeks after the viral clearance from the upper respiratory tract in COVID-19 patients [8] . To clarify the above questions, we performed a retrospective study to detect the presence of SARS-CoV-2 virions and determine the pathological changes in rectal tissues of this patient. Samples of rectal tissues, succus entericus and intestinal mucosa of ileostomy, and rectal mucosa were tested for SARS-CoV-2 nucleic acid using qRT-PCR. abstract: BACKGROUND: Currently, there is no direct evidence to prove the active SARS-CoV-2 replication in the intestinal tract and relevant pathological changes in the colon and rectum. We investigated the presence of virions and pathological changes in surgical rectal tissues of a clinically confirmed COVID-19 patient with rectal adenocarcinoma. METHODS: Here, the clinical data were collected during hospitalization and follow-up of this patient. Quantitative RT-PCR was performed on the rectal tissue specimens obtained from surgical resection, succus entericus and intestinal mucosa of ileostomy, and rectal mucosa during follow-up after recovery. Ultrathin sections of surgical samples were observed for SARS-CoV-2 virions using electron microscopy. Histopathological examination was performed using hematoxylin-eosin stain. Immunohistochemical analysis and immunofluorescence were carried out on rectal tissues to evaluate the distribution of SARS-CoV-2 antigen, and immune cell infiltrations. RESULTS: The patient had fever and cough on day 3 postoperatively, was diagnosed with COVID-19 on day 7, and was discharged from the hospital on day 41. RNA of SARS-CoV-2 was detected in surgically resected rectal specimens, but not in samples collected on 37 day after discharge. Notably, coincidence with rectal tissues of surgical specimens tested nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Moreover, abundant lymphocytes and macrophages (some are SARS-CoV-2 positive) infiltrating the lamina propria were found with no significant mucosal damage. CONCLUSIONS: We firstly reported that direct evidence of the active SARS-CoV-2 replication in the patient's rectum during the incubation period, which might explain SARS-CoV-2 fecal-oral transmission. url: https://doi.org/10.1093/cid/ciaa925 doi: 10.1093/cid/ciaa925 id: cord-290792-ggcz1zfw author: Qutob, N. title: Seroprevalence of SARS-CoV-2 in Palestine: a cross-sectional seroepidemiological study date: 2020-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Seroprevalence rates are important indicators to the epidemiology of Covid-19 and the rates vary according to the population. In Palestine, there is lack of data on the the percentage of undiagnosed population with previous mild or asymptomatic COVID-19. The purpose of this study is to assess the seroprevalence rate in the Palestinian population residing in the West Bank. Blood samples were collected from1319 adults from Palestinian households in the West Bank and 1136 individuals visiting laboratories for a routine checkup. Serological tests for the 2455 serum samples were done using an Immunoassay for the qualitative detection of antibodies against SARS-CoV-2 .The random sample of Palestinians living in the West Bank yielded 0% seroprevalence with 95% CI [0,0.0036], while the lab referrals sample yielded 4 positive cases. Hence the estimated seroprevalence in this sample is 0.354% with 95% CI [0.0011,0096]. Our results indicate that seroprevalence persist low and is inadequate to provide herd immunity and emphasize the need to maintain health measures to keep the outbreak under control. url: http://medrxiv.org/cgi/content/short/2020.08.28.20180083v1?rss=1 doi: 10.1101/2020.08.28.20180083 id: cord-329190-kv9n2qj3 author: Rabaan, Ali A. title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date: 2017-09-01 words: 8886.0 sentences: 433.0 pages: flesch: 44.0 cache: ./cache/cord-329190-kv9n2qj3.txt txt: ./txt/cord-329190-kv9n2qj3.txt summary: The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including ''Middle East respiratory syndrome coronavirus'', ''MERS-CoV'', ''SARS'', ''therapy'', ''molecular'', ''vaccine'', ''prophylactic'', ''S protein'', ''DPP4'', ''heptad repeat'', ''protease'', ''inhibitor'', ''anti-viral'', ''broad-spectrum'', ''interferon'', ''convalescent plasma'', ''lopinavir ritonavir'', ''antibodies'', ''antiviral peptides'' and ''live attenuated viruses''. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] . abstract: There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including ‘Middle East respiratory syndrome coronavirus’, ‘MERS-CoV’, ‘SARS’, ‘therapy’, ‘molecular’, ‘vaccine’, ‘prophylactic’, ‘S protein’, ‘DPP4’, ‘heptad repeat’, ‘protease’, ‘inhibitor’, ‘anti-viral’, ‘broad-spectrum’, ‘interferon’, ‘convalescent plasma’, ‘lopinavir ritonavir’, ‘antibodies’, ‘antiviral peptides’ and ‘live attenuated viruses’. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies. url: https://doi.org/10.1099/jmm.0.000565 doi: 10.1099/jmm.0.000565 id: cord-275252-4e3cn50u author: Rad SM, Ali Hosseini title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 words: 4368.0 sentences: 302.0 pages: flesch: 53.0 cache: ./cache/cord-275252-4e3cn50u.txt txt: ./txt/cord-275252-4e3cn50u.txt summary: In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. A common primary focus of mutational analysis of emerging viruses is the alteration in amino acid sequence of viral proteins that may provide enhanced or new functions for virus replication, immune avoidance, or spread. However, the potential of these mutations to impact upon RNA structure and miRNA recognition provides a basis for ongoing monitoring of viral evolution at these sites in the SARS-CoV-2 genome. abstract: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. url: https://doi.org/10.1101/2020.05.15.098947 doi: 10.1101/2020.05.15.098947 id: cord-311114-ggcpsjk8 author: Radhakrishnan, Chandni title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 words: 4383.0 sentences: 274.0 pages: flesch: 52.0 cache: ./cache/cord-311114-ggcpsjk8.txt txt: ./txt/cord-311114-ggcpsjk8.txt summary: The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. In our analysis, we mapped the SARS-CoV-2 genetic variants obtained from Kerala genomes to the 132 primer or probes sequence and calculated the melting temperature (Tm) of the mutant with the wild type sequence. abstract: Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. Genomic approaches have been extensively used to understand the evolution and epidemiology of SARS-CoV-2 across the world. Kerala is a unique state in India well connected with the rest of the world through a large number of expatriates, trade, and tourism. The first case of COVID-19 in India was reported in Kerala in January 2020, during the initial days of the pandemic. The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. We sequenced a total of 200 samples from patients at a tertiary hospital in Kerala using COVIDSeq protocol at a mean coverage of 7,755X. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. The genomes formed a monophyletic distribution exclusively mapping to the A2a clade. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. To the best of our knowledge, this is the first and most comprehensive report of genetic epidemiology and evolution of SARS-CoV-2 isolates from Kerala. url: https://doi.org/10.1101/2020.09.09.289892 doi: 10.1101/2020.09.09.289892 id: cord-334564-bqh9jkds author: Raony, Ícaro title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date: 2020-05-27 words: 9893.0 sentences: 464.0 pages: flesch: 41.0 cache: ./cache/cord-334564-bqh9jkds.txt txt: ./txt/cord-334564-bqh9jkds.txt summary: Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) . abstract: Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues. url: https://doi.org/10.3389/fimmu.2020.01170 doi: 10.3389/fimmu.2020.01170 id: cord-323093-u3ozc9ry author: Rathnayake, Athri D. title: 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice date: 2020-08-19 words: 7158.0 sentences: 362.0 pages: flesch: 56.0 cache: ./cache/cord-323093-u3ozc9ry.txt txt: ./txt/cord-323093-u3ozc9ry.txt summary: After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection. abstract: Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32747425/ doi: 10.1126/scitranslmed.abc5332 id: cord-336150-l8w7xk0b author: Rathore, Jitendra Singh title: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: an overview date: 2020-08-25 words: 7362.0 sentences: 399.0 pages: flesch: 54.0 cache: ./cache/cord-336150-l8w7xk0b.txt txt: ./txt/cord-336150-l8w7xk0b.txt summary: The essential surface glycoprotein of SARS-CoV-2 known as spike (S) protein, essential for host cell receptor binding, showed only 72% similarity with SARS-CoV at the nucleotide level. Comparative genome analysis of RaTG13, a virus from a Rhinolophusaffinis (i.e. horseshoe) bat sampled from Yunnan province in China in 2013, with SARS-CoV-2, showed that SARS-CoV-2 has 96% similarity at the nucleotide sequence level . Later, it was found that the disease was caused by a virus designated as a novel human coronavirus, MERS-CoV, phylogenetic data showed that it belonged to lineage C of the Betacoronavirusgenus and was highly similar to bat coronaviruses HKU4 (Tylonycterispachypus) and HKU5 (Pipistrelluspipistrellus; Lau et al. When cell lines over-expressed the transmembrane protein ''angiotensin-converting enzyme 2'' (ACE2) from humans, bats, pig or civet cats and were infected with SARS-CoV-2, results showed that they became hypersensitized to infection, thus indicating that ACE2 is a SARS-CoV-2 receptor . Recently, neutralizing monoclonal antibodies and nanobodies against the RBD domain of S protein showed protection against SARS-CoV and MERS-CoV (Du et al. abstract: Coronavirus disease 2019 (COVID-19) is a viral pneumonia, responsible for the recent pandemic, and originated from Wuhan, China, in December 2019. The causative agent of the outbreak was identified as coronavirus and designated as severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Few years back, the severe acute respiratory syndrome coronavirus (SARS- CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were reported to be highly pathogenic and caused severe infections in humans. In the current situation SARS-CoV-2 has become the third highly pathogenic coronavirus that is responsible for the present outbreak in human population. At the time of this review, there were more than 14 007 791 confirmed COVID-19 patients which associated with over 597 105 deaths in more then 216 countries across the globe (as reported by World Health Organization). In this review we have discussed about SARS-CoV, MERS-CoV and SARC-CoV-2, their reservoirs, role of spike proteins and immunogenicity. We have also covered the diagnosis, therapeutics and vaccine status of SARS-CoV-2. url: https://doi.org/10.1093/femspd/ftaa042 doi: 10.1093/femspd/ftaa042 id: cord-350557-7i7122zi author: Rawlings, Stephen A title: No Evidence of SARS-CoV-2 Seminal Shedding Despite SARS-CoV-2 Persistence in the Upper Respiratory Tract date: 2020-08-07 words: 1750.0 sentences: 115.0 pages: flesch: 57.0 cache: ./cache/cord-350557-7i7122zi.txt txt: ./txt/cord-350557-7i7122zi.txt summary: We evaluated the presence and level of SARS-CoV-2 RNA in semen, nasal secretion, and saliva collected after confirmed infection. SARS-CoV-2 RNA was not detected in semen 6–17 days after the onset of symptoms despite concomitant shedding in oral secretions. Here, we evaluated the presence and level of SARS-CoV-2 in paired semen, nasal secretion, and saliva samples collected in the short and medium term after confirmed SARS-CoV-2 symptomatic infections. Before enrollment, 5/6 participants tested positive for SARS-CoV-2 RNA on NP swab samples collected within 1-3 days following the onset of symptoms. Upon enrollment in the study, the diagnosis of active SARS-CoV-2 infection was confirmed by positive PCR on NP swab on day 6 post-symptom onset. We found no evidence of SARS-CoV-2 in semen collected 6-17 days after the onset of symptoms despite all men having concomitant shedding of virus in oral secretions up to 792 copies/µL. abstract: RNA viruses (eg, Zika, Ebola, HIV) are often shed in male genital secretions. We evaluated the presence and level of SARS-CoV-2 RNA in semen, nasal secretion, and saliva collected after confirmed infection. SARS-CoV-2 RNA was not detected in semen 6–17 days after the onset of symptoms despite concomitant shedding in oral secretions. url: https://www.ncbi.nlm.nih.gov/pubmed/32875005/ doi: 10.1093/ofid/ofaa325 id: cord-254446-yxqbe1dj author: Ren, Yunzhao R. title: A Comprehensive Updated Review on SARS‐CoV‐2 and COVID‐19 date: 2020-05-29 words: 6723.0 sentences: 426.0 pages: flesch: 49.0 cache: ./cache/cord-254446-yxqbe1dj.txt txt: ./txt/cord-254446-yxqbe1dj.txt summary: The disease name -COVID-19‖ and the associated virus name -SARS-CoV-2‖ were coined by the World Health Organization (WHO) and the Coronavirus Study Group of the International Committee on Virus Taxonomy, respectively, on February 11 1, 2 . Interestingly, pharyngeal swab viral nucleic acid screening results of 2,510 patients between January 23 and February 25 from a hospital fever clinic in Hunan Province (a neighboring province of Hubei) demonstrated that the positive rate of SARS-CoV-2 (1.3%) was lower than that of Influenza A (2.3%) and Influenza B (3.3%) 42 . Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial abstract: This literature review aims to provide a comprehensive current summary of the pathogenesis, clinical features, disease course, host immune responses, and current investigational antiviral and immunomodulatory pharmacotherapies, in order to facilitate the development of future therapies and measures for prevention and control. This article is protected by copyright. All rights reserved url: https://www.ncbi.nlm.nih.gov/pubmed/32469437/ doi: 10.1002/jcph.1673 id: cord-313505-2lr4xara author: Resende, Paola Cristina title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 words: 1145.0 sentences: 99.0 pages: flesch: 55.0 cache: ./cache/cord-313505-2lr4xara.txt txt: ./txt/cord-313505-2lr4xara.txt summary: title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. Introduction 59 COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 60 (SARS-CoV-2), is leading to high rates of acute respiratory syndrome, hospitalization, and death 61 genomes (> 10% of ambiguous positions), we obtained a final dataset of 7,674 sequences. The prevalence of the sub-clade 211 B.1.1 in our sample (92%) was much higher than that observed in other Brazilian sequences 212 available in GISAID (36%) (Fig. 1C) phylogenetic tree, consistent with the hypothesis of multiple independent introductions (Fig. 2) (Fig. 2) . Revealing COVID-19 Transmission by SARS-CoV-2 Genome 410 Sequencing and Agent Based Modelling. abstract: Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil. url: https://doi.org/10.1101/2020.06.17.158006 doi: 10.1101/2020.06.17.158006 id: cord-346539-kxnrf5g5 author: Riggioni, Carmen title: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 date: 2020-06-14 words: 15760.0 sentences: 1112.0 pages: flesch: 48.0 cache: ./cache/cord-346539-kxnrf5g5.txt txt: ./txt/cord-346539-kxnrf5g5.txt summary: This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. The first cases of the coronavirus disease 2019 (COVID19) , caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), were reported in China in December 2019 1 and rapidly led to pandemic. 40, 41 A seroconversion study in COVID-19 patients has found and association between disease severity and SARS-CoV-2-specific IgA levels. Mesenchymal stem cell therapy may potentiate the low IFN-I and -III levels and moderate IFN-stimulated gene response reported in SARS-CoV-2-infected ferrets and COVID-19 patients. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial abstract: In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socio‐economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo‐embolic complications and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19‐related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32535955/ doi: 10.1111/all.14449 id: cord-291397-look6ddt author: Roberto, Palumbo title: Current treatment of COVID-19 in renal patients: hope or hype? date: 2020-09-28 words: 5827.0 sentences: 326.0 pages: flesch: 46.0 cache: ./cache/cord-291397-look6ddt.txt txt: ./txt/cord-291397-look6ddt.txt summary: Given the lack of specific therapy about the ongoing SARS-CoV-2 infection, we conducted a brief review to summarize the mechanism of action and the potentially side effects of the treatment currently available, focusing on the effects of the drugs on renal disease at different stages in terms of therapeutic management and survival. A randomized clinical trial, handled by a Chinese group, suggested that in hospitalized adult patients with severe infection, no benefit was observed with lopinavir/ritonavir beyond standard care in terms of time to clinical improvement, reduction of mortality and safety (side effects and discontinuation of treatment) [29, 30] . Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial abstract: To date the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), known as COVID-19, is for clinicians the most difficult global therapeutic problem. In this landscape, the management of patients with chronic kidney disease, acute kidney injury or patients undergoing immunosuppressant therapies for kidney transplant or glomerular diseases, represent a clinical challenge for nephrologists, especially in patients with severe acute lung involvement. Therefore in this setting, due to the lack of anti-COVID treatment schedules, tailored management is mandatory to reduce the side effects, as consequence of impaired renal function and drugs interactions. We report the main treatment actually used against SARS-CoV-2, underlining its possible use in the nephropatic patients and the central role of nephrologists to improve the clinical outcome. url: https://doi.org/10.1007/s11739-020-02510-0 doi: 10.1007/s11739-020-02510-0 id: cord-314451-mqnqjn0c author: Roberts, Anjeanette title: A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date: 2007-01-12 words: 9794.0 sentences: 433.0 pages: flesch: 48.0 cache: ./cache/cord-314451-mqnqjn0c.txt txt: ./txt/cord-314451-mqnqjn0c.txt summary: To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. abstract: No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals. url: https://www.ncbi.nlm.nih.gov/pubmed/17222058/ doi: 10.1371/journal.ppat.0030005 id: cord-321901-zpi7uis1 author: Roberts, Anjeanette title: Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK date: 2006-11-30 words: 6600.0 sentences: 311.0 pages: flesch: 40.0 cache: ./cache/cord-321901-zpi7uis1.txt txt: ./txt/cord-321901-zpi7uis1.txt summary: Scientists at the WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, discussed many aspects of research pertaining to the use of animal models in vaccine development including available animal models, suitability of the various models, correlates of protection, critical components of potential vaccines, and the potential for disease enhancement in vaccinated animals following exposure to SARS-CoV. It may actually be worthwhile to enhance the virulence of a SARS-CoV isolate by serial passages in an animal model to produce a challenge virus stock for vaccine studies that would elicit more reproducible disease in the animals. Although none of the studies to date have shown enhanced respiratory disease following SARS-CoV challenge in previously immunized animals, further studies in this area are warranted in view of some of the available in vitro data. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice abstract: Abstract Severe acute respiratory syndrome (SARS) emerged in the Guangdong province of China in late 2002 and spread to 29 countries. By the end of the outbreak in July 2003, the CDC and WHO reported 8437 cases with a 9.6% case fatality rate. The disease was caused by a previously unrecognized coronavirus, SARS-CoV. Drawing on experience with animal coronavirus vaccines, several vaccine candidates have been developed and evaluated in pre-clinical trials. Available data suggest that vaccines should be based on the the 180kDa viral spike protein, S, the only significant neutralization antigen capable of inducing protective immune responses in animals. In the absence of clinical cases of SARS, candidate vaccines should be evaluated for efficacy in animal models, and although it is uncertain whether the United States Food and Drug Administration's “animal rule” would apply to licensure of a SARS vaccine, it is important to develop standardized animal models and immunological assays in preparation for this eventuality. This report summarizes the recommendations from a WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25–26 August 2005 in South Mimms, UK, provides guidance on the use of animal models, and outlines the steps to develop standard reagents and assays for immunological evaluation of candidate SARS vaccines. url: https://www.sciencedirect.com/science/article/pii/S0264410X06008231 doi: 10.1016/j.vaccine.2006.07.009 id: cord-347706-r0rs3ls1 author: Roberts, Anjeanette title: Animal Models for Sars date: 2006 words: 3013.0 sentences: 139.0 pages: flesch: 43.0 cache: ./cache/cord-347706-r0rs3ls1.txt txt: ./txt/cord-347706-r0rs3ls1.txt summary: Mice that recover from infection develop a neutralizing antibody response and are protected from subsequent challenge; antibody alone is sufficient to protect mice from replication of SARS-CoV in the lower respiratory tract and NK, NK-T, T, and B cells are not required for viral clearance. 13, 13b CoV disease, with weight loss and pneumonitis that begins with acute bronchiolitis and In summary, SARS-CoV replicates efficiently in the respiratory tract of young viremia occurs 1 to 2 days following infection and virus is detected in the liver and spleen in hamsters. As seen with the other animal models, the course of infection in experimentally infected nonhuman primates is short, with a rapid peak in viral replication and clearance of virus from the lungs by days 4 to 7 in different species. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/17037579/ doi: 10.1007/978-0-387-33012-9_83 id: cord-309633-1cd74xdl author: Rogers, Julia H. title: Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study date: 2020-09-15 words: 4018.0 sentences: 241.0 pages: flesch: 53.0 cache: ./cache/cord-309633-1cd74xdl.txt txt: ./txt/cord-309633-1cd74xdl.txt summary: MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. Surge testing was initiated on 30 March 2020 (and continued through 24 April) in collaboration with Public Health-Seattle & King County''s Communicable Disease Epidemiology Team to conduct contact tracing at 6 shelters where cases of SARS-CoV-2 were previously detected ( Figure 2 ). We calculated the test positivity rate of SARS-CoV-2 infection at shelters by dividing the number of positive cases by the total number of participant encounters in the study period. Overall, 2% of participant encounters involved positive SARS-CoV-2 results, with most cases detected through surge testing events. abstract: BACKGROUND: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. OBJECTIVE: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. DESIGN: Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917) SETTING: 14 homeless shelters in King County, Washington. PARTICIPANTS: A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. INTERVENTION: Two strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing (“surge testing”) events. MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. RESULTS: Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. LIMITATION: Selection bias due to voluntary participation and a relatively small case count. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. PRIMARY FUNDING SOURCE: Gates Ventures. url: https://doi.org/10.7326/m20-3799 doi: 10.7326/m20-3799 id: cord-287501-7it4kh0e author: Roh, Changhyun title: A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide date: 2012-05-03 words: 2964.0 sentences: 153.0 pages: flesch: 45.0 cache: ./cache/cord-287501-7it4kh0e.txt txt: ./txt/cord-287501-7it4kh0e.txt summary: We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. 33 In this study, we report a novel approach for the inhibitor screening of SARS-CoV N protein using a quantum dots (QDs)-conjugated oligonucleotide system with wide applicability for facile and sensitive imaging analysis on a biochip. To the best of our knowledge, this is the first report on the inhibition effects of (-)-catechin gallate and (-)-gallocatechin gallate on SARS-CoV N protein using an optical nanoparticle-based RNA oligonucleotide platform. Among the polyphenolic compounds screened, (-)-catechin gallate and (-)-gallocatechin gallate showed high anti-SARS-CoV N protein activity. At a concentration of 0.05 µg mL -1 , (-)-catechin gallate and (-)-gallocatechin gallate showed more than 40% inhibition activity on a QDs-RNA oligonucleotide biochip platform. abstract: Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (−)-catechin gallate and (−)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL(−1), (−)-catechin gallate and (−)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system. url: https://doi.org/10.2147/ijn.s31379 doi: 10.2147/ijn.s31379 id: cord-350992-l6l24pco author: Roldan, Eugenia Quiros title: The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? date: 2020-05-13 words: 8037.0 sentences: 393.0 pages: flesch: 40.0 cache: ./cache/cord-350992-l6l24pco.txt txt: ./txt/cord-350992-l6l24pco.txt summary: Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. We also propose a different insight into some of CQ and HCQ effects, suggesting a potential role of iron homeostasis in Sars-Cov-2 disease (COVID-19), similarly to several other human viral infections [2] [3] [4] . The search strategy was to use different search terms alone and in any combination, such as "Sars-Cov-2 disease", "COVID-19", "Sars-Cov-2", "coronavirus", "clinical trial", "treatment", "drug", "chloroquine", "hydroxychloroquine", "iron", "virus", "viral entry", "viral spread", "anti-viral activity", "infection", "inflammation", "immunity", "innate immunity", "cytokine", "IL-6", "TNF-", "IL-1", "adaptive immunity", "thrombosis", "in vitro". abstract: The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course. url: https://www.sciencedirect.com/science/article/pii/S1043661820312123?v=s5 doi: 10.1016/j.phrs.2020.104904 id: cord-278618-7tu5c7m1 author: Romano-Bertrand, Sara title: Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission? date: 2020-06-12 words: 1340.0 sentences: 70.0 pages: flesch: 45.0 cache: ./cache/cord-278618-7tu5c7m1.txt txt: ./txt/cord-278618-7tu5c7m1.txt summary: This is based on previous knowledge [1] and the doctrine that: a patient positive for SARS-CoV-2 is contagious by respiratory secretions (>10μm in size) that disseminate only on short distance (<1m); SARS-CoV-2 carried on large droplets settles onto local surfaces and is not stable in the air; SARS-CoV-2 aerosol dispersion is possible during AGPs which extensively expose HCWs and therefore HCWs need to wear a respirator for a higher respiratory protection during AGPs. However, an experimental study of van Doremalen et al, [2] assessed the sustainability of SARS-CoV-2 in aerosols (<5μm at 65% of hygrometry (expressed in %RH for relative humidity)) performed using a high-powered machine that does not reflect normal cough conditions (https://www.who.int/publications-detail/modes-of-transmission-of-virus-causing-covid-19-implicationsfor-ipc-precaution-recommendations). They showed that SARS-CoV-2 remained viable and infective at least 3 hours in aerosols, which opened the debate on SARS-CoV-2 transmission through longdistance aerosols (>1m), and questioned the appropriateness of respiratory protection for HCWs. An individual who is well, emits 10 to 10 4 particles per liter of expired air, including 95% of <1μm-size particles [3] . abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0195670120303030?v=s5 doi: 10.1016/j.jhin.2020.06.018 id: cord-356009-emn2w8if author: Roshandel, M. R. title: What Specimen Urologists Should Be Most Concerned About ? A Systematic Review and Meta-Analysis date: 2020-10-13 words: 4687.0 sentences: 292.0 pages: flesch: 49.0 cache: ./cache/cord-356009-emn2w8if.txt txt: ./txt/cord-356009-emn2w8if.txt summary: Conclusions: Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight ?percent of patients but also its incidence may have associations with the severity of the ?systemic disease, ICU admission, and fatality rates. The searches included medical subject headings (MeSH) and keywords for SARS-CoV-2, COVID, Corona, together with shedding, persistence, urine, urinary, specimen, viral load, or RNA body fluids. We completed the data abstraction process using created forms to record study characteristics, clinical data, and laboratory data including study year and design, country of study origin, total initial population size, test type for disease diagnosis, test type for samples (urine/stool/rectal swab/blood), patients age (including mean and range), number of positive and total patients and/or (wherever applicable) number of positive and total specimens collected for each test category, disease severity, ICU admission, and fatality rate. abstract: Objective:Investigating the infectivity of body fluid can be useful for preventative measures in the community and ensuring safety in the operating rooms and on the laboratory practices. Methods:We performed a literature search of clinical trials, cohorts, and case series using PubMed/MEDLINE, Google Scholar, and Cochrane library, and downloadable database of CDC. We excluded case reports and searched all language articles for review and repeated until the final drafting. The search protocol was registered in the PROSPERO database. Results: Thirty studies with urinary sampling for viral shedding were included. A total number of 1,271 patients were enrolled initially, among which 569 patients had undergone urinary testing. Nine studies observed urinary viral shedding in urine from 41 patients. The total incidence of urinary SARS-CoV-2 shedding was 8%, compared to 21.3% and 39.5 % for blood and stool, respectively. The summarized risk ratio (RR) estimates for urine positive rates compared to the pharyngeal rate was 0.08. The pertaining RR urine compared to blood and stool positive rates were 0.20 and 0.33 respectively. Conclusions: Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight ?percent of patients but also its incidence may have associations with the severity of the ?systemic disease, ICU admission, and fatality rates. Moreover, the findings in our review ?suggest that a larger population size may reveal more positive urinary cases possibly by ?minimizing biases. However, it is important to notice that it is the naso-pharyngeal specimens, ?stool, and serum that show more possibilities to became positive, respectively. url: https://doi.org/10.1101/2020.10.08.20209544 doi: 10.1101/2020.10.08.20209544 id: cord-309289-vm0k7hfx author: Rothan, Hussin A. title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 words: 1463.0 sentences: 91.0 pages: flesch: 46.0 cache: ./cache/cord-309289-vm0k7hfx.txt txt: ./txt/cord-309289-vm0k7hfx.txt summary: title: The FDAapproved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, antiinflammatory and anti-ROS properties. We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury. abstract: SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use. url: https://doi.org/10.1101/2020.04.14.041228 doi: 10.1101/2020.04.14.041228 id: cord-262276-5nue46dm author: Roussel, Yanis title: SARS-CoV-2: fear versus data date: 2020-03-19 words: 1860.0 sentences: 119.0 pages: flesch: 55.0 cache: ./cache/cord-262276-5nue46dm.txt txt: ./txt/cord-262276-5nue46dm.txt summary: The first, severe acute respiratory syndrome (SARS) coronavirus, had very little impact on global morbidity and mortality, with more than 80 0 0 recognized cases and 774 deaths [15 , 16] . Among the Organisation for Economic Co-operation and Development (OECD) countries, 7476 patients have tested positive for SARS-CoV-2, with 96 deaths (mortality rate 1.3%) ( Table 3 ). In France, 191 people have tested positive for SARS-CoV-2, with three deaths (mortality rate 1.6%). If the extrapolation of deaths in AP-HM hospitals is correct, in metropolitan France, this would represent 543/0.8 * 100 = 67 875 cases of patients hospitalized with a respiratory infection with common coronaviruses in 2 months, which is almost as many cases as for SARS-CoV-2 worldwide. Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China abstract: SARS-CoV-2, the novel coronavirus from China, is spreading around the world, causing a huge reaction despite its current low incidence outside China and the Far East. Four common coronaviruses are in current circulation and cause millions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-CoV-2 in Organisation for Economic Co-operation and Development countries. It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing. url: https://www.ncbi.nlm.nih.gov/pubmed/32201354/ doi: 10.1016/j.ijantimicag.2020.105947 id: cord-029813-o2uzcuai author: Rusconi, Stefano title: COVID-19: studying the global pandemic – foreword date: 2020-07-27 words: 2723.0 sentences: 131.0 pages: flesch: 43.0 cache: ./cache/cord-029813-o2uzcuai.txt txt: ./txt/cord-029813-o2uzcuai.txt summary: This special issue of Future Virology contains nine articles on diverse aspects of the COVID-19 pandemic and its causative agent, SARS-CoV-2. The topics range from basic virology on coronavirus evolution and replication to identification of repurposed therapeutics for clinical testing to public health issues including the conundrums of asymptomatic viral transmission and risks to homeless populations. The Commentary by Parvez [1] briefly reviews the detection of SARS-CoV-2 RNA in fecal samples, including its persistence, and the finding of gastrointestinal complaints in a minority of hospitalized patients. While it is clear that this phytochemical has multiple pharmacological activities, as reviewed previously [10] , this in silico report does not provide biologic data on rutin''s possible effects in SARS-CoV-2 infection. Detection of relatively high SARS-CoV-2 RNA loads in upper respiratory tract samples has been reported in both presymptomatic (late incubation period) and truly asymptomatic infected persons. Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386404/ doi: 10.2217/fvl-2020-0211 id: cord-158628-71n1tgrw author: Russo, Giulia title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform date: 2020-05-05 words: 5596.0 sentences: 296.0 pages: flesch: 50.0 cache: ./cache/cord-158628-71n1tgrw.txt txt: ./txt/cord-158628-71n1tgrw.txt summary: Recently, specific findings about the genome sequencing of SARS-CoV-2 in different countries where cases of infection were registered, revealed its relative intrinsic genomic variability, its virus dynamics and the related host response mechanisms, unveiling interesting knowledge useful for the formulation of innovative strategies for preventive vaccination. Specifically, SARS-CoV-2 sequencing along with its relative intrinsic genomic variability [10] , the presence of minority variants generated during SARS-CoV-2 replication [11] , the involved cellular factors that favors SARS-CoV-2 cell entry [12] , the timing in which viral load peaks (during the first week of illness), its gradual decline (over the second week) and the increasing of both IgG and IgM antibodies (around day 10 after symptom onset) represent some of the relevant insights so far delineated and considered by research community about SARS-CoV-2 virus [13] . UISS is an immune system simulation platform that was designed to be applied to several and different scenarios, especially to carry on in silico trials to predict the efficacy of a specific prophylactic or therapeutic vaccine against a particular disease. abstract: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS- CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. UISS is then potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2. url: https://arxiv.org/pdf/2005.02289v1.pdf doi: nan id: cord-344714-0cam9ipf author: Russo, Maria title: Roles of flavonoids against coronavirus infection date: 2020-07-28 words: 8395.0 sentences: 394.0 pages: flesch: 46.0 cache: ./cache/cord-344714-0cam9ipf.txt txt: ./txt/cord-344714-0cam9ipf.txt summary: Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL(pro), 3CL(pro), NTPase/helicase. Inhibition of TMPRSS2 and Furin protease activities can be considered an interesting therapeutic option against coronavirus infection, especially COVID-19, allowing the block and/or prevention of SARS-CoV-2 infection, as recently reported [28] . Based on these observations, it is not surprising that molecular docking approach, summarized in Fig. 3 , supports the role of flavonoids in the inhibition of SARS-CoV 3CL pro by binding His41 and Cys145 of the catalytic site and other active site residues (e.g., Met49, Gly143, His163, His164, Glu166, Pro168, and Gln89), stimulating their validation by in vitro and in vivo studies. abstract: In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of “savage” protocols, based on “old” anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenols family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PL(pro), 3CL(pro), NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections. url: https://doi.org/10.1016/j.cbi.2020.109211 doi: 10.1016/j.cbi.2020.109211 id: cord-286269-vrjyj2y1 author: Sagheb, Setareh title: Two seriously ill neonates born to mothers with COVID-19 pneumonia- a case report date: 2020-09-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19), a highly contagious viral disease has spread from Wuhan, Hubei Province, China to all over the world from its first recognition on December 2019. To date, only a few neonatal early-onset sepsis by SARS-COV-2 has been reported worldwide. CASE PRESENTATION: In this report, we present two seriously ill neonates who were born from mothers with stablished COVID-19 pneumonia. Laboratory tests showed lymphopenia with high LDH and hypocalcemia right after the birth. They had fever for days without responding to antibiotics and despite ruling out other potential causes. Both patients had positive RTPCR for SARS-COV-2 in the second round of testing but the first assay tested was negative. Hydroxychloroquine was used to treat both patients; the first patient was treated with it over a period of 14 days before showing signs of improvement. The second patient responded to the treatment over a period of 5 days. CONCLUSION: Although based on the available evidences, vertical transmission of COVID-19 is less likely, many aspects of pathogenesis and transmission of this novel virus are still unclear. Therefore we cannot rule out the vertical transmission totally. Further investigations are warranted to determine the exact mechanisms and routes of transmission. url: https://doi.org/10.1186/s13052-020-00897-2 doi: 10.1186/s13052-020-00897-2 id: cord-337089-ksh62ni0 author: Salajegheh Tazerji, Sina title: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review date: 2020-09-21 words: 4901.0 sentences: 293.0 pages: flesch: 53.0 cache: ./cache/cord-337089-ksh62ni0.txt txt: ./txt/cord-337089-ksh62ni0.txt summary: In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. However, based on recently published findings, other authors hypothesized that an immunological cross-protection between SARS-CoV-2 and canine respiratory coronavirus (CRCoV) exists due to the high homology between the spike protein epitopes of the two taxonomicallyrelated coronaviruses [21] . The objective of the present study was to gather, present, and discuss information on the reported cases of COVID-19 in animals focusing on the virus transmission cases in pets and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. abstract: COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal–human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32957995/ doi: 10.1186/s12967-020-02534-2 id: cord-335652-v98gv5uf author: Salazar, Cecilia title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date: 2020-05-10 words: 2063.0 sentences: 131.0 pages: flesch: 48.0 cache: ./cache/cord-335652-v98gv5uf.txt txt: ./txt/cord-335652-v98gv5uf.txt summary: Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. This global health emergency has deployed international efforts to apply genomic epidemiology to track the spread of SARS-CoV-2 in real time. The recent development of targeted sequencing protocols by the ARTIC Network [3] , open sharing of genomic data through the GISAID (www.gisaid.org) database and straightforward bioinformatic tools for viral phylogenomics [4] , provides the opportunity to reconstruct global spatio-temporal dynamics of the COVID-19 pandemic with unprecedented comprehensiveness and resolution. We therefore aimed to characterize the spatio-temporal dynamics of SARS-CoV-2 by sequencing around 10% of cases occurred during the first week of outbreak in Montevideo, allowing us to identify transmission patterns, geographic origins and genetic variation among local strains. abstract: Background After its emergence in China in December 2019, the new coronavirus disease (COVID-19) caused by SARS-CoV-2, has rapidly spread infecting more than 3 million people worldwide. South America is among the last regions hit by COVID-19 pandemic. In Uruguay, first cases were detected on March 13 th 2020 presumably imported by travelers returning from Europe. Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Then, we applied genomic epidemiology using a global dataset to reconstruct the local spatio-temporal dynamics of SARS-CoV-2. Results Our phylogeographic analysis showed three independent introductions of SARS-CoV-2 from different continents. Also, we evidenced regional circulation of viral strains originally detected in Spain. Introduction of SARS-CoV-2 in Uruguay could date back as early as Feb 20th. Identification of specific mutations showed rapid local genetic differentiation. Conclusions We evidenced early independent introductions of SARS-CoV-2 that likely occurred before first cases were detected. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. url: https://doi.org/10.1101/2020.05.09.086223 doi: 10.1101/2020.05.09.086223 id: cord-332595-874tpi09 author: Salehi, Najmeh title: Profiling of Initial Available SARS-CoV-2 Sequences from Iranian Related COVID-19 Patients date: 2020-09-08 words: 1800.0 sentences: 111.0 pages: flesch: 61.0 cache: ./cache/cord-332595-874tpi09.txt txt: ./txt/cord-332595-874tpi09.txt summary: To this purpose, SARS-CoV-2 full genome sequence profiling of 20 patients in Iran and different countries that already had a travel history to Iran or contacts with Iranian cases were provided from the GISAID database. The bioinformatics analysis showed 44 different nucleotide mutations that caused 26 nonsynonymous mutations in protein sequences with regard to the reference full genome of the SARS-CoV-2 sequence (NC_045512.2). On the other hand, nineteen sequences of the full genome sequence of SARS-CoV-2 on the GISAID database from patients in different countries that had a travel history to Iran or contacts with Iranian cases were retrieved from the database. In this study, the full genome sequences of SARS-CoV-2 from the 20 Iranian related COVID-19 patients were profiled in detail. B. The nucleotide and protein mutations, the number of mutation events in data from the 20 Iranian related patients, the entropy values of these mutations in all 3927 SARS-CoV-2 sequences, and the corresponded proteins are depicted. abstract: The etiologic agent SARS-CoV-2 has caused the outbreak of COVID-19 which is spread widely around the world. It is vital to uncover and investigate the full genome sequence of SARS-CoV-2 throughout the world to track changes in this virus. To this purpose, SARS-CoV-2 full genome sequence profiling of 20 patients in Iran and different countries that already had a travel history to Iran or contacts with Iranian cases were provided from the GISAID database. The bioinformatics analysis showed 44 different nucleotide mutations that caused 26 nonsynonymous mutations in protein sequences with regard to the reference full genome of the SARS-CoV-2 sequence (NC_045512.2). R207C, V378I, M2796I, L3606F, and A6407V in ORF1ab were common mutations in these sequences. Also, some of the detected mutations only were found in Iranian data in comparison with all the available sequences of SARS-CoV-2. The position of S protein mutations showed they were far from the binding site of this protein with angiotensin-converting enzyme-2 (ACE2) as the host cell receptor. These results can be helpful to design specific diagnostic tests, trace the SARS-CoV-2 sequence changes in Iran, and explore therapeutic drugs and vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/32779445/ doi: 10.22074/cellj.2020.7524 id: cord-273451-xnce010o author: Salisbury-Afshar, Elizabeth M. title: Vulnerable Populations: Weathering the Pandemic Storm date: 2020-04-22 words: 1658.0 sentences: 97.0 pages: flesch: 47.0 cache: ./cache/cord-273451-xnce010o.txt txt: ./txt/cord-273451-xnce010o.txt summary: Yet, even with awareness that all individuals deserve access to services, and that supporting marginalized populations will slow the spread of SARS-CoV-2, resource limitations will demand difficult allocation determinations. 3 Many individuals experiencing homelessness with SARS-CoV-2 will not meet hospitalization criteria and will be discharged into the general population. 11 In response to SARS-CoV-2, the Substance Abuse and Mental Health Services Administration has developed emergency regulations to support medication for opioid use disorder via telehealth, 12 and temporarily waived the requirement for in-person physical exam to be able to initiate buprenorphine. These often forgotten populations-people incarcerated, homeless, or using drugs-are likely to experience higher risk of exposure to SARS-CoV-2 because of their social circumstances. Planning should incorporate dedicated efforts, funding, and policies/guidelines specific to individuals who experience homelessness, are incarcerated, or are coping with substance use disorders both because these populations deserve care and services, and because not doing so poses great risk to the broader community. abstract: nan url: https://doi.org/10.1016/j.amepre.2020.04.002 doi: 10.1016/j.amepre.2020.04.002 id: cord-267134-5gz2dotn author: Sallenave, Jean-Michel title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date: 2020-05-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described “cytokine storm” and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically. url: https://www.ncbi.nlm.nih.gov/pubmed/32574272/ doi: 10.3389/fimmu.2020.01229 id: cord-025119-201ac32t author: Salman, Saad title: Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors date: 2020-05-21 words: 3144.0 sentences: 162.0 pages: flesch: 37.0 cache: ./cache/cord-025119-201ac32t.txt txt: ./txt/cord-025119-201ac32t.txt summary: Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Here, we analyzed different medicinal compounds using a virtual screening method to obtain promising inhibitors for these viral proteins that could be further utilized for SARS-COV-2 treatment. More than 300 medicinal compounds with immunomodulatory and antiviral activity were added to the Raccoon2 plugin of Autodock vina to perform virtual screening to obtain promising inhibitors for SARS-COV-2 proteins. This study aimed to obtain novel drug candidates that have the capability to interact with the active site of all of these viral proteins and should possess efficient pharmacokinetic profile with low toxicity to ensure safety during administration. • Docking interaction of immunomodulatory medicinal compounds library filtered six promising medicinal compounds against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) viral proteins. abstract: Aim: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a pernicious viral disease, causes acute respiratory distress responsible for mortality and morbidity worldwide. To screen different immunomodulatory medicinal compounds to unravel their interaction with SARS-COV-2 viral proteins. Materials & methods: A library of immunomodulatory medicinal compounds with antiviral capability were analyzed against SARS proteases, spike protein and nonstructural proteins (NSP-9, 15) using Autodock vina. Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Further ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis showed good pharmacokinetic properties and low acute toxicity of these compounds. Conclusion: The current study provides convincing evidence that these medicinal compounds exert antiviral activity against the SARS-COV-2 virus and could be further exploited for the treatment of this disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243912/ doi: 10.2217/fvl-2020-0079 id: cord-340049-6rqmc89u author: Salvatori, Giovanni title: SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines date: 2020-06-03 words: 1411.0 sentences: 86.0 pages: flesch: 44.0 cache: ./cache/cord-340049-6rqmc89u.txt txt: ./txt/cord-340049-6rqmc89u.txt summary: Evidence of the key role played by the S protein in counteracting coronavirus infection came from studies on human-neutralizing antibodies from rare memory B cells of individuals infected with SARS-CoV [2] or MERS-CoV [3] . Journal of Translational Medicine antibody responses, and vigorously neutralized SARS-CoV-2 S-mediated entry into cells, thus further encouraging the use of this molecular target for vaccination and immunotherapies [4] . Given the above and that the coronavirus S glycoprotein is surface-exposed and mediates entry into host cells by interacting with angiotensin-converting enzyme 2 (ACE2), it rapidly became the main target of neutralizing antibodies and the focus of therapeutic and vaccine design. Several companies and research institutes have started developing a vaccine that has the SARS-CoV-2 protein S as its target (see Table 1 ), although the various vaccination strategies show a differing ability to induce in the host both an antibody-mediated humoral response and a cell response mediated by CD4 or CD8 T lymphocytes in preclinical models. abstract: COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies. url: https://www.ncbi.nlm.nih.gov/pubmed/32493510/ doi: 10.1186/s12967-020-02392-y id: cord-334550-xb0alubj author: Samaddar, Arghadip title: The Enigma of Low COVID-19 Fatality Rate in India date: 2020-07-28 words: 6405.0 sentences: 367.0 pages: flesch: 48.0 cache: ./cache/cord-334550-xb0alubj.txt txt: ./txt/cord-334550-xb0alubj.txt summary: These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. Researchers from Translational Bioinformatics Group at International Center for Genetic Engineering and Biotechnology (ICGEB) in collaboration with the Department of Biochemistry, Jamia Hamdard, New Delhi, India, performed an integrated mutational analysis of SARS-CoV-2 genomes from different geographical locations, including India, Italy, United States, Nepal and Wuhan, and observed a novel mutation in S protein (A930V, 24351C>T) of the Indian strain, which was absent in other strains (Sardar et al., 2020) . While this apparent protection among Indians is largely attributed to non-heritable influences as discussed earlier, a safe and effective vaccine against SARS-CoV-2 can reduce disease severity, control transmission, and prevent future infections across all populations. abstract: Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic. Though its origin has been linked to the Wuhan City of China’s Hubei Province in December 2019, recent reports claim that the original animal-to-human transmission of the virus probably happened sometime between September and October 2019 in Guangdong Province, rather than Hubei. As of July 3, 2020, India has reported a case positivity rate of 6.5% and a fatality rate of 2.8%, which are among the lowest in the world. Also, the severity of the disease is much less among Indians as evidenced by the low rate of ICU admission (15.3%) and the need for mechanical ventilation (4.16%). As per the World Health Organization (WHO) situation report 165 on July 3, 2020, India has one of the lowest deaths per 100,000 population (1.32 deaths against a global average of 6.04). Several factors related to the pathogen, host and environment might have some role in reducing the susceptibility of Indians to COVID-19. These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. This perspective -highlights the potential factors that might be responsible for the observed low COVID-19 fatality rate in Indian population. It puts forward several hypotheses which can be a ground for future studies determining individual and population susceptibility to COVID-19 and thus, may offer a new dimension to our current understanding of the disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32849833/ doi: 10.3389/fgene.2020.00854 id: cord-259229-e8m8m4ut author: Samidurai, Arun title: Cardiovascular Complications Associated with COVID-19 and Potential Therapeutic Strategies date: 2020-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The outbreak of coronavirus disease 2019 (COVID-19), an infectious disease with severe acute respiratory syndrome, has now become a worldwide pandemic. Despite the respiratory complication, COVID-19 is also associated with significant multiple organ dysfunction, including severe cardiac impairment. Emerging evidence reveals a direct interplay between COVID-19 and dire cardiovascular complications, including myocardial injury, heart failure, heart attack, myocarditis, arrhythmias as well as blood clots, which are accompanied with elevated risk and adverse outcome among infected patients, even sudden death. The proposed pathophysiological mechanisms of myocardial impairment include invasion of SARS-CoV-2 virus via angiotensin-converting enzyme 2 to cardiovascular cells/tissue, which leads to endothelial inflammation and dysfunction, de-stabilization of vulnerable atherosclerotic plaques, stent thrombosis, cardiac stress due to diminish oxygen supply and cardiac muscle damage, and myocardial infarction. Several promising therapeutics are under investigation to the overall prognosis of COVID-19 patients with high risk of cardiovascular impairment, nevertheless to date, none have shown proven clinical efficacy. In this comprehensive review, we aimed to highlight the current integrated therapeutic approaches for COVID-19 and we summarized the potential therapeutic options, currently under clinical trials, with their mechanisms of action and associated adverse cardiac events in highly infectious COVID-19 patients. url: https://doi.org/10.3390/ijms21186790 doi: 10.3390/ijms21186790 id: cord-289588-n61gz7pi author: Samudrala, Pavan Kumar title: Virology, pathogenesis, diagnosis and in-line treatment of COVID-19 date: 2020-07-17 words: 3898.0 sentences: 253.0 pages: flesch: 56.0 cache: ./cache/cord-289588-n61gz7pi.txt txt: ./txt/cord-289588-n61gz7pi.txt summary: Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. As far as safety is a major concern, 424 Gilead Sciences announced phase III clinical trial of remdesivir to prove its safety and 425 efficacy in COVID-19 infection (Keown, 16 .03.2020). Epidemiology, causes, clinical manifestation and 687 diagnosis, prevention and control of coronavirus disease (COVID-19) during the early 688 outbreak period: a scoping review First known person-to-784 person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 785 the USA Clinical 803 features of patients infected with 2019 novel coronavirus in Wuhan SARS-CoV-2 (COVID-19) Vaccine Development and Production: An 817 Severe acute respiratory 845 syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The 846 epidemic and the challenges Unique epidemiological and clinical features 949 of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control 950 measures abstract: SARS-CoV-2, a newly emerged pathogen in December 2019, marked as one of the highly pathogenic Coronavirus, and altogether this is the third coronavirus attack that crossed the species barrier. As of 1(st) July 2020, it is spreading around 216 countries, areas or territories, and a total of 10,185,374 and 503,862 confirmed cases and death reports, respectively. The SARS-CoV-2 virus entered into the target cells by binding with the hACE2 receptors. Spike glycoprotein promotes the entry of the virus into host target cells. Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. These modifications may be the probable reason for the extreme transmission and pathogenicity of the virus. A hasty spread of COVID-19 throughout the world is highly threatening, but still, scientists do not have a proper therapeutic measure to fight with it. Scientists are endeavoring across the world to find effective therapy to combat COVID 19. Several drugs such as Remdesivir, Hydroxychloroquine, Chloroquine, Ribavirin, Ritonavir, Lopinavir, Favipiravir, Interferons, Bevacizumab, Azithromycin, etc. are currently under clinical trials. Vaccine development from various pharmaceutical companies and research institutes is under progress, and more than ten vaccine candidates are in the various phases of clinical trials. This review work highlighted the origin, emergence, structural features, pathogenesis, and clinical features of COVID-19. We have also discussed the in-line treatment strategies, preventive measures, and vaccines to combat the emergence of COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0014299920304672?v=s5 doi: 10.1016/j.ejphar.2020.173375 id: cord-293691-ewerquin author: Sauerhering, Lucie title: Cyclophilin Inhibitors Restrict Middle East Respiratory Syndrome Coronavirus Via Interferon λ In Vitro And In Mice date: 2020-07-02 words: 3428.0 sentences: 191.0 pages: flesch: 43.0 cache: ./cache/cord-293691-ewerquin.txt txt: ./txt/cord-293691-ewerquin.txt summary: RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. To address the previously proposed antiviral activity of CsA in clinically relevant cells, we infected the human bronchial epithelial cell line Calu-3 and primary human alveolar epithelial cells (hAEC) with MERS-CoV and analyzed intracellular viral RNA and infectious particle release in presence of DMSO or CsA ( Figure 1 ). Our data demonstrated that silencing of IRF1 but not treatment by control siRNA lead to a significant increase in MERS-CoV released viral particles in CsA-treated cells ( Figure 6A , B). abstract: RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. OBJECTIVES: We elucidated the molecular mechanisms by which the cyclophilin inhibitors Cyclosporin A (CsA) and Alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily-available therapy in MERS-CoV infection. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by qRT-PCR and TCID(50). Data were validated in a murine MERS-CoV infection model. RESULTS: CsA and ALV both reduced MERS-CoV titers and viral RNA replication in Calu-3 and hAEC improving epithelial integrity. While neither Calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type-III-interferon (IFNλ) response and expression of antiviral genes. Down-regulation of IRF1 or IFNλ increased MERS-CoV propagation in presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome. CONCLUSIONS: We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory, antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate to treat MERS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32616594/ doi: 10.1183/13993003.01826-2019 id: cord-024133-zv0ysi8m author: Saxena, Shailendra K. title: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) date: 2020-04-30 words: 2220.0 sentences: 142.0 pages: flesch: 49.0 cache: ./cache/cord-024133-zv0ysi8m.txt txt: ./txt/cord-024133-zv0ysi8m.txt summary: On 11 March 2020, the World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic that causes novel coronavirus disease 2019 (COVID-19) (World Health Organization 2020a). In addition, the scientific fraternity worldwide has been continuously working on COVID-19 from the beginning by publishing the genome and developing highly specific diagnostic tools for the detection of SARS-CoV-2 infection. There is no specific treatment available for SARS-CoV-2 and the current treatment relies on supportive care of the infected patients (Centre for Disease Control and Prevention 2020b). Fig. 1.3 Steps needed to be taken by COVID-19 patients in order to prevent the spread of SARS-CoV-2 infection Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19). Centre for Disease Control and Prevention (2020b) Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). abstract: SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189397/ doi: 10.1007/978-981-15-4814-7_1 id: cord-309474-9h9w46eq author: Schiaffini, Riccardo title: School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology date: 2020-07-03 words: 2515.0 sentences: 118.0 pages: flesch: 52.0 cache: ./cache/cord-309474-9h9w46eq.txt txt: ./txt/cord-309474-9h9w46eq.txt summary: We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. This is a real-life, retrospective, observational study aimed at evaluating how constant parental care compared to spending time outside home affected glycemic control in pre-school and school children with T1D utilizing Tandem Basal IQ system before and during the quarantine period due to pandemic COVID-19 infection. Our observational real-life study confirms the positive effect of parental care in T1D very young children and that, though new technologies can potentially improve diabetes outcomes also in this sub-population, maintenance of a good glucose control remains largely dependent on family competence and education 10. abstract: Abstract Introduction Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. Aim of the study To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic. Patients and methods 22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. Results During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6 % vs 34,73 ± 12,8 %. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day – p<0.05). Conclusion Our observational real-life study confirms the positive effect of parental care in T1D very young children and demonstrates that during the COVID-19 pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle. url: https://www.ncbi.nlm.nih.gov/pubmed/32623034/ doi: 10.1016/j.diabres.2020.108302 id: cord-124012-5zxkd2jy author: Schwab, Patrick title: predCOVID-19: A Systematic Study of Clinical Predictive Models for Coronavirus Disease 2019 date: 2020-05-17 words: 5098.0 sentences: 247.0 pages: flesch: 38.0 cache: ./cache/cord-124012-5zxkd2jy.txt txt: ./txt/cord-124012-5zxkd2jy.txt summary: Here, we study clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test, require hospitalisation or intensive care. In addition, [48] performed a cohort study for clinical and laboratory predictors of COVID-19 related inhospital mortality that identified baseline neutrophil count, age Fig. 2 : The presented multistage machine-learning pipeline consists of preprocessing (light purple) the input data x, developing multiple candidate models using the given dataset (orange), selecting the best candidate model for evaluation (blue), and evaluating the selected best model''s outputsŷ. Owing to the recent emergence of SARS-CoV-2, there currently exists, to the best of our knowledge, no prior systematic study on clinical predictive models that predict likelihood of a positive SARS-CoV-2 test, hospital and intensive care unit admission from clinical, demographic and blood analysis data that accounts for the missingness that is characteristic for the clinical setting. abstract: Coronavirus Disease 2019 (COVID-19) is a rapidly emerging respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the rapid human-to-human transmission of SARS-CoV-2, many healthcare systems are at risk of exceeding their healthcare capacities, in particular in terms of SARS-CoV-2 tests, hospital and intensive care unit (ICU) beds and mechanical ventilators. Predictive algorithms could potentially ease the strain on healthcare systems by identifying those who are most likely to receive a positive SARS-CoV-2 test, be hospitalised or admitted to the ICU. Here, we study clinical predictive models that estimate, using machine learning and based on routinely collected clinical data, which patients are likely to receive a positive SARS-CoV-2 test, require hospitalisation or intensive care. To evaluate the predictive performance of our models, we perform a retrospective evaluation on clinical and blood analysis data from a cohort of 5644 patients. Our experimental results indicate that our predictive models identify (i) patients that test positive for SARS-CoV-2 a priori at a sensitivity of 75% (95% CI: 67%, 81%) and a specificity of 49% (95% CI: 46%, 51%), (ii) SARS-CoV-2 positive patients that require hospitalisation with 0.92 AUC (95% CI: 0.81, 0.98), and (iii) SARS-CoV-2 positive patients that require critical care with 0.98 AUC (95% CI: 0.95, 1.00). In addition, we determine which clinical features are predictive to what degree for each of the aforementioned clinical tasks. Our results indicate that predictive models trained on routinely collected clinical data could be used to predict clinical pathways for COVID-19, and therefore help inform care and prioritise resources. url: https://arxiv.org/pdf/2005.08302v1.pdf doi: nan id: cord-284867-p4jgyusp author: Schöler, Lara title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 words: 4328.0 sentences: 235.0 pages: flesch: 42.0 cache: ./cache/cord-284867-p4jgyusp.txt txt: ./txt/cord-284867-p4jgyusp.txt summary: Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. The fact that the infection and the resulting icELISA signal were neutralized by NAbs present in immune sera indicated that the fast and automated icELISA format is applicable for icNTs. Although most SARS-CoV-2 NTs have not been formally validated and certified, classic plaque reduction neutralization tests (PRNT) are currently considered to represent the gold standard for the detection of SARS-CoV-2-specific NAbs. Various commercially available IgM, IgA, and IgG ELISAs have been compared to PRNTs [e.g., (30) ]. Given the excellent signal-to-noise ratio between infected and uninfected cells, the test was applicable to quantify the efficacy of antiviral compounds, here shown for IFNb, and SARS-CoV-2-specific NAbs present in immune sera. abstract: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most pressing medical and socioeconomic challenge. Constituting important correlates of protection, the determination of virus-neutralizing antibodies (NAbs) is indispensable for convalescent plasma selection, vaccine candidate evaluation, and immunity certificates. In contrast to standard serological ELISAs, plaque reduction neutralization tests (PRNTs) are laborious, time-consuming, expensive, and restricted to specialized laboratories. To replace microscopic counting-based SARS-CoV-2 PRNTs by a novel assay exempt from genetically modified viruses, which are inapplicable in most diagnostics departments, we established a simple, rapid, and automated SARS-CoV-2 neutralization assay employing an in-cell ELISA (icELISA) approach. After optimization of various parameters such as virus-specific antibodies, cell lines, virus doses, and duration of infection, SARS-CoV-2-infected cells became amenable as direct antigen source for quantitative icELISA. Antiviral agents such as human sera containing NAbs or antiviral interferons dose dependently reduced the SARS-CoV-2-specific signal. Applying increased infectious doses, the icELISA-based neutralization test (icNT) was superior to PRNT in discriminating convalescent sera with high from those with intermediate neutralizing capacities. In addition, the icNT was found to be specific, discriminating between SARS-CoV-2-specific NAbs and those raised against other coronaviruses. Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. url: https://doi.org/10.3389/fimmu.2020.573526 doi: 10.3389/fimmu.2020.573526 id: cord-324919-ciamusjs author: Scialo, Filippo title: ACE2: The Major Cell Entry Receptor for SARS-CoV-2 date: 2020-11-10 words: 5356.0 sentences: 257.0 pages: flesch: 42.0 cache: ./cache/cord-324919-ciamusjs.txt txt: ./txt/cord-324919-ciamusjs.txt summary: Since the beginning of the COVID-19 pandemic, hypertension and diabetes have been correlated with higher risk of mortality, and initial reports speculated that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), which are commonly used therapeutic agents for these conditions, would up-regulate ACE2 expression, thus increasing the risk of severe illness [37] . Binding of S1 subunit of the Spike protein of SARS-CoV-2 to the ACE2 receptor triggers the cleavage of ACE2 by ADAM17/tumor necrosis factorconverting enzyme (TACE) at the ectodomain sites [41] and a soluble form that retains its catalytic activity (sACE2) is produced [42] . ACE2 shedding can be stimulated by proinflammatory cytokines such as IL-1β and tumor necrosis factor (TNF)-α, and endotoxin [47] that could result in a positive effect reducing SARS-CoV-2 entry, but at the same time, may cause an increase in AngII and further activation of the AngII/AT1R axis worsening inflammation (discussed below) (Fig. 1) . Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) abstract: Despite the unprecedented effort of the scientific community, the novel SARS-CoV-2 virus has infected more than 46 million people worldwide, killing over one million two hundred thousand. Understanding the mechanisms by which some individuals are more susceptible to SARS-CoV-2 infection and why a subgroup of them are prone to experience severe pneumonia, and death should lead to a better approach and more effective treatments for COVID-19. Here, we focus our attention on ACE2, a primary receptor of SARS-CoV-2. We will discuss its biology, tissue expression, and post-translational regulation that determine its potential to be employed by SARS-CoV-2 for cell entry. Particular attention will be given to how the ACE2 soluble form can have a great impact on disease progression and thus be used in a potential therapeutic strategy. Furthermore, we will discuss repercussions that SARS-CoV-2/ACE2 binding has on the renin–angiotensin system and beyond. Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin–kallikrein system regulating coagulation and inflammation. Thorough comprehension of the role that ACE2 plays in different pathways will be the key to assess the impact that SARS-CoV-2/ACE2 binding has on organismal physiology and will help us to find better therapies and diagnostic tools. url: https://doi.org/10.1007/s00408-020-00408-4 doi: 10.1007/s00408-020-00408-4 id: cord-284589-j1609xlu author: Sedova, Mayya title: Coronavirus3D: 3D structural visualization of COVID-19 genomic divergence date: 2020-05-29 words: 1302.0 sentences: 85.0 pages: flesch: 55.0 cache: ./cache/cord-284589-j1609xlu.txt txt: ./txt/cord-284589-j1609xlu.txt summary: RESULTS: Coronavirus3D website integrates data on the SARS-CoV-2 virus mutations with information about 3D structures of its proteins, allowing users to visually analyze the mutations in their 3D context. At the same time, with the exception of the spike protein mutations, there are no publicly available resources that provide analysis for all the other structurally characterized regions of the SARS-CoV-2 proteins. For commercial re-use, please contact journals.permissions@oup.com MN908947.3), with information on boundaries of the predicted proteins, currently available SARS-CoV-2 structures and a histogram of the aminoacid mutation frequency. The first of the lower level panels (Figure 1b) provides interactive visualization of the selected structure or model, with an option for coloring the chain according to the mutation frequency. The Coronavirus3D server was designed to provide users with information and tools to carry out their own analysis of how mutations in the SARS-CoV-2 proteins may affect their 3D-structures and their functions. abstract: MOTIVATION: As the COVID-19 pandemics is spreading around the world, the SARS-CoV-2 virus is evolving with mutations that potentially change and fine-tune functions of the proteins coded in its genome. RESULTS: Coronavirus3D website integrates data on the SARS-CoV-2 virus mutations with information about 3D structures of its proteins, allowing users to visually analyze the mutations in their 3D context. AVAILABILITY: Coronavirus3D server is freely available at https://coronavirus3d.org. url: https://doi.org/10.1093/bioinformatics/btaa550 doi: 10.1093/bioinformatics/btaa550 id: cord-309418-dx6e0lri author: Segalés, Joaquim title: Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain date: 2020-10-06 words: 3135.0 sentences: 178.0 pages: flesch: 48.0 cache: ./cache/cord-309418-dx6e0lri.txt txt: ./txt/cord-309418-dx6e0lri.txt summary: Several models for SARS-CoV-2 infection have been so far developed in animals, including Egyptian fruit bat, ferret, golden Syrian hamster, cat, humanized angiotensin-converting enzyme 2 (ACE2) transgenic mice (hACE2 mice), and some nonhuman primate species (3) (4) (5) (6) (7) (8) . The clinical condition was finally attributed to a feline hypertrophic cardiomyopathy, but the animal was also infected by SARS-CoV-2. The detection of SARS-CoV-2 RNA in several samples of C1, all of them with Ct values over 30 (low viral load), and presence of antibodies (neutralizing and nonneutralizing) in both C1 and C2, indicated both animals suffered from a productive viral infection, probably linked to the exposure of the cats to COVID-19−affected owners. These experimental results, together with the few reports on SARS-CoV-2 detection in domestic cats and wild felids, indicate that felines are susceptible to infection by the novel coronavirus. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19−like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia. url: https://doi.org/10.1073/pnas.2010817117 doi: 10.1073/pnas.2010817117 id: cord-315085-rucfowvv author: Sekulic, Miroslav title: Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases date: 2020-05-26 words: 5025.0 sentences: 302.0 pages: flesch: 47.0 cache: ./cache/cord-315085-rucfowvv.txt txt: ./txt/cord-315085-rucfowvv.txt summary: In this study we report postmortem findings and detection and sequencing of SARS-CoV-2 viral RNA from formalin-fixed paraffinembedded (FFPE) samples of multiple organs collected in 2 patients with antemortem detection of SARS-CoV-2. The patient''s medical history was otherwise notable for dementia, radiologic evidence of a left lung mass (managed with hospice care), coronary artery disease (status post coronary artery bypass grafting), atrial fibrillation (biventricular pacemaker implanted), congestive heart failure, peripheral artery disease (status post iliac stenting), diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, gout, smoking, cerebrovascular accidents, and urinary tract infections. On day 1 after admission, ❚Image 2❚ (Case 1) Postmortem microscopic examination of the lungs showed diffuse alveolar damage characterized by hyaline membrane formation (A, ×100) and scattered squamous metaplasia of distal airways (B, ×100) on a background of emphysematous changes. abstract: OBJECTIVES: To report methods and findings of 2 autopsies with molecular evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals. METHODS: Postmortem examination was completed following Centers for Disease Control and Prevention public guidelines. Numerous formalin-fixed paraffin-embedded (FFPE) tissue types from each case were surveyed for SARS-CoV-2 RNA by quantitative reverse transcription polymerase chain reaction (qRT-PCR). SARS-CoV-2 viral genome was sequenced by next-generation sequencing (NGS) from FFPE lung tissue blocks. RESULTS: Postmortem examinations revealed diffuse alveolar damage, while no viral-associated hepatic, cardiac, or renal damage was observed. Viral RNA was detected in lungs, bronchi, lymph nodes, and spleen in both cases using qRT-PCR method. RNA sequencing using NGS in case 1 revealed mutations most consistent with Western European Clade A2a with ORF1a L3606F mutation. CONCLUSIONS: SARS-CoV-2 testing and viral sequencing can be performed from FFPE tissue. Detection and sequencing of SARS-CoV-2 in combination with morphological findings from postmortem tissue examination can aid in gaining a better understanding of the virus’s pathophysiologic effects on human health. url: https://doi.org/10.1093/ajcp/aqaa091 doi: 10.1093/ajcp/aqaa091 id: cord-342756-rgm9ffpk author: Senger, Mario Roberto title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery date: 2020-10-02 words: 16108.0 sentences: 1024.0 pages: flesch: 51.0 cache: ./cache/cord-342756-rgm9ffpk.txt txt: ./txt/cord-342756-rgm9ffpk.txt summary: Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment. abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/33027420/ doi: 10.1590/0074-02760200254 id: cord-268483-joiajgs4 author: Shah, Vibhuti Kumar title: Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date: 2020-08-07 words: 10644.0 sentences: 477.0 pages: flesch: 43.0 cache: ./cache/cord-268483-joiajgs4.txt txt: ./txt/cord-268483-joiajgs4.txt summary: As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. An ELISA-based time kinetics study to detect the COVID-19 specific humoral immune response showed that the patients produced IgM and IgG antibodies that did not cross-react with other human coronaviruses except SARS-CoV. A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65) . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice abstract: After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19. url: https://doi.org/10.3389/fimmu.2020.01949 doi: 10.3389/fimmu.2020.01949 id: cord-331472-kd4uxcve author: Shahid, Zainab title: COVID‐19 and Older Adults: What We Know date: 2020-04-20 words: 2314.0 sentences: 153.0 pages: flesch: 53.0 cache: ./cache/cord-331472-kd4uxcve.txt txt: ./txt/cord-331472-kd4uxcve.txt summary: Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). 5 The Centers for Disease Control and Prevention (CDC) reported that although individuals older than age 65 comprise 17% of the total population in the United States, they make up 31% of COVID-19 infections, 45% of hospitalizations, 53% of intensive care unit admissions, and 80% of deaths caused by this infection. 15, 16 These symptoms are also common in older adults; one study on 21 critically ill patients with SARS-CoV-2 infection, with a mean age of 70 years, found that the most common presenting symptoms were shortness of breath (76%), fever (52%), and cough (48%). 19 One study on 46 fatal cases of SARS-CoV-2, in which 84% of patients were older than age 60, found that diabetes is likely associated with increased mortality. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a novel virus that causes COVID‐19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE‐2 receptor, the very receptor that the SARS‐CoV‐2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID‐19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID‐19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926–929, 2020 url: https://doi.org/10.1111/jgs.16472 doi: 10.1111/jgs.16472 id: cord-314669-lvibjx97 author: Shang, Guifang title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 date: 2007-11-26 words: 4044.0 sentences: 186.0 pages: flesch: 53.0 cache: ./cache/cord-314669-lvibjx97.txt txt: ./txt/cord-314669-lvibjx97.txt summary: title: Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 STUDY DESIGN AND METHODS: Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. RESULTS: Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. Theoretically estimated risk of severe acute respiratory syndrome transmission through blood transfusion during an epidemic in Shenzhen, Guangdong, China in 2003 Then, using this information and information on the asymptomatic or subclinical SARS-CoV infection-to-clinically confirmed SARS ratio (R), the proportion of infected individuals who remain asymptomatic (A), and the population size, we estimated the risk of SARS-CoV transmission by transfusion from a unit of blood donated at time t during the epidemic. abstract: BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that caused an outbreak in south China in 2003. The cause of SARS was identified as a novel coronavirus (CoV). The existence of asymptomatic seroconvertors and the detection of the SARS-CoV RNA in plasma during the course of infection all suggest that SARS could, as least theoretically, be transmitted by transfusion. An estimate of the risk of SARS transmission through blood transfusion will contribute to decisions concerning blood safety monitoring and may be useful in the design of strategies to decrease the risk of transfusion-transmitted infections. STUDY DESIGN AND METHODS: Case onset dates from the 2003 Shenzhen SARS epidemic and investigational results from Taiwan on viremia in humans are used to estimate the number of cases that were viremic throughout the epidemic. Estimates of the asymptomatic-to-clinically confirmed SARS-CoV infection ratio, the proportion of asymptomatic infections reported in a seroprevalence survey in Hongkong, and the population size of Shenzhen are used to infer the SARS-CoV transfusion–transmission risk. Statistical resampling methods are used. RESULTS: Based on data from Shenzhen, Hongkong and Taiwan, the maximum and mean risk (per million) of SARS-CoV transmission from donors in Shenzhen were estimated as 23.57 (95% CI: 6.83–47.69) and 14.11 (95% CI: 11.00–17.22), respectively. The estimated risk peaked on April 02, 2003. CONCLUSIONS: Although there are currently no confirmed reports of the transmission of SARS-CoV from asymptomatic individuals, recent research data indicate that transfusion-transmitted SARS-CoV is at least theoretically possible. Although the risk is low, with its rapid spread of the disease, appearance of alarmingly high infectivity and high fatality rate, public health authorities need to consider strategies for blood donor recruitment and virus inactivation during an epidemic to further ensure blood safety. url: https://www.ncbi.nlm.nih.gov/pubmed/18036985/ doi: 10.1016/j.transci.2007.09.004 id: cord-305856-xt3zxajf author: Shanmugam, Chandrakumar title: COVID-2019 – A comprehensive pathology insight date: 2020-09-18 words: 4597.0 sentences: 325.0 pages: flesch: 46.0 cache: ./cache/cord-305856-xt3zxajf.txt txt: ./txt/cord-305856-xt3zxajf.txt summary: Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. The current pandemic of corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2) led to complete lockdown in many countries contributing to major socio-economic crisis and irreparable recession, globally. [22, 31, 32, 33] Similar to SARS CoV, a recent study reported non-O blood group specifically group A had higher infection and death rates due to COVID-19 owing to absence of protective anti-A IgM antibodies. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer The clinical pathology of severe acute respiratory syndrome (SARS): a report from China abstract: Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. The lungs are the main organs affected leading to pneumonia and respiratory failure in severe cases that may need mechanical ventilation. Occasionally patient may present with gastro-intestinal, cardiac and neurologic symptoms with or without lung involvement. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. Other organs like liver and kidneys may be involved secondarily. Currently the treatment is principally symptomatic and prevention by proper use of personal protective equipment and other measures is crucial to limit the spread. In the midst of pandemic there is paucity of literature on pathological features including pathogenesis, hence in this review we provide the current pathology centered understanding of COVID-19. Furthermore, the pathogenetic pathway is pivotal in the development of therapeutic targets. url: https://www.ncbi.nlm.nih.gov/pubmed/32979742/ doi: 10.1016/j.prp.2020.153222 id: cord-268388-kkhuzf3p author: Sharif-Yakan, Ahmad title: Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date: 2014-12-04 words: 2507.0 sentences: 141.0 pages: flesch: 50.0 cache: ./cache/cord-268388-kkhuzf3p.txt txt: ./txt/cord-268388-kkhuzf3p.txt summary: Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/25474536/ doi: 10.1371/journal.ppat.1004457 id: cord-324480-7u5lh4jx author: Sharma, A. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 words: 1541.0 sentences: 88.0 pages: flesch: 51.0 cache: ./cache/cord-324480-7u5lh4jx.txt txt: ./txt/cord-324480-7u5lh4jx.txt summary: Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. However an understanding of how SARS-CoV-2 survives different environmental conditions is still incomplete and mechanisms of virus particle degradation are poorly mapped out. A key challenge in studying SARS-CoV-2 is the extreme level of threat associated with the live virus and the resultant need for high safety standards for such work. Here we used this technology to study the stability of the viral envelope and associated proteins (M, E, and S) under different environmental conditions. Environmental stability of SARS-CoV-2 on different types of surfaces under indoor and seasonal climate conditions abstract: SARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. Statement of Scientific Significance The economic and public health impact of the COVID-19 pandemic are very significant. However scientific information needed to underpin policy decisions are limited partly due to novelty of the SARS-CoV-2 pathogen. There is therefore an urgent need for mechanistic studies of both COVID-19 disease and the SARS-CoV-2 virus. We show that individual virus particles suffer structural destabilization at relatively mild but elevated temperatures. Our nanoscale results are consistent with recent observations at larger scales. Our work strengthens the case for COVID-19 resurgence in winter. url: https://doi.org/10.1101/2020.10.12.336818 doi: 10.1101/2020.10.12.336818 id: cord-033551-eojpkxz9 author: Shekh, Shamasoddin title: In silico allicin induced S-thioallylation of SARS-CoV-2 main protease date: 2020-09-16 words: 3910.0 sentences: 248.0 pages: flesch: 54.0 cache: ./cache/cord-033551-eojpkxz9.txt txt: ./txt/cord-033551-eojpkxz9.txt summary: In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 M(pro) using PX-12 as a benchmark reference compound. Figure 1a shows the structure of SARS-CoV-2 M pro with free cysteine thiols and active site dyad residues. Figure 2b shows the formation of cysteine allyl disulfide at the Cys-145 residue of SARS-CoV-2 M pro after covalent docking with allicin. Figure 4b and c show the formation of cysteine allyl disulfide at Cys-85 and Cys-156 residue of SARS-CoV-2 M pro after covalent docking with allyl sulfenic acid. Table-S2 provides a summary of covalent docking of allicin/PX-12/allyl sulfenic acid at cysteine thiols of four different co-crystal structures of SARS-CoV-2 M pro . Figure 5b shows the sulfur mediated hydrogen bonding by the sulfur of allyl disulfide formed after covalent docking of allicin at the active site of SARS-CoV-2 M pro . abstract: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused due to new coronavirus infection with (3)716075 deaths across the world as reported by the World Health Organization (WHO). SARS-CoV-2 main protease (M(pro)) plays a vital role in the replication of coronavirus and thus an attractive target for the screening of inhibitors for the therapy of COVID-19. The preclinical drugs ebselen and PX-12 are potent inhibitors of SARS-CoV-2 M(pro) and covalently modifies the active site Cys-145 residue of M(pro) through selenosulfide/disulfide. In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 M(pro) using PX-12 as a benchmark reference compound. The results indicate that allicin induces dual S-thioallylation of Cys-145 and Cys-85/ Cys-156 residues of SARS-CoV-2 M(pro). Using density functional theory (DFT), Gibbs free energy change (DG) is calculated for the putative reactions between N-acetylcysteine amide thiol and allicin/allyl sulfenic acid. The overall reaction is exergonic and allyl disulfide of Cys-145 residue of M(pro) is involved in a sulfur mediated hydrogen bond. The results indicate that allicin causes dual S-thioallylation of SARS-CoV-2 M(pro) which may be of interest for treatment and attenuation of ongoing coronavirus infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544924/ doi: 10.1080/17415993.2020.1817457 id: cord-325966-0g7a9s5z author: Shih, Hsin-I. title: Fighting COVID-19: a quick review of diagnoses, therapies, and vaccines date: 2020-05-30 words: 7324.0 sentences: 365.0 pages: flesch: 39.0 cache: ./cache/cord-325966-0g7a9s5z.txt txt: ./txt/cord-325966-0g7a9s5z.txt summary: Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. However, these clinical, laboratory, and imaging findings are nonspecific and cannot differentiate COVID-19 from other viral respiratory infections; viral diagnostic methods specific for SARS-CoV-2 should be applied for disease confirmation. An open-label study published in 2004 suggested, by comparison with a control group that received only ribavirin, that the addition of lopinavir-ritonavir (400 mg and 100 mg, respectively) to ribavirin reduced the risk of adverse clinical outcomes (acute respiratory distress syndrome or death) and viral load among patients with SARS [29] . Some available candidate drugs targeting different levels of human responses to COVID-19, such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, IL-6 blocker and convalescent plasma, may improve the clinical outcomes of critical COVID-19 patients. abstract: The COVID-19 pandemic caused by a novel coronavirus, SARS-CoV-2, has infected more than 4.9 million individuals and resulted in over 300,000 deaths globally. The rapid spread of the virus and the precipitously increasing numbers of cases necessitate the urgent development of accurate diagnostic methods, effective treatments, and vaccines. Here, we review the progress of developing diagnostic methods, therapies, and vaccines for SARS-CoV-2 with a focus on current clinical trials and their challenges. For diagnosis, nucleic acid amplification tests remain the mainstay diagnostics for laboratory confirmation of SARS-CoV-2 infection, while serological antibody tests are used to aid contact tracing, epidemiological, and vaccine evaluation studies. Viral isolation is not recommended for routine diagnostic procedures due to safety concerns. Currently, no single effective drug or specific vaccine is available against SARS-CoV-2. Some candidate drugs targeting different levels and stages of human responses against COVID-19 such as cell membrane fusion, RNA-dependent RNA polymerase, viral protease inhibitor, interleukin 6 blocker, and convalescent plasma may improve the clinical outcomes of critical COVID-19 patients. Other supportive care measures for critical patients are still necessary. Advances in genetic sequencing and other technological developments have sped up the establishment of a variety of vaccine platforms. Accordingly, numerous vaccines are under development. Vaccine candidates against SARS-CoV-2 are mainly based upon the viral spike protein due to its vital role in viral infectivity, and most of these candidates have recently moved into clinical trials. Before the efficacy of such vaccines in humans is demonstrated, strong international coordination and collaboration among studies, pharmaceutical companies, regulators, and governments are needed to limit further damage due the emerging SARS-CoV-2 virus. url: https://doi.org/10.1016/j.bj.2020.05.021 doi: 10.1016/j.bj.2020.05.021 id: cord-254636-3lr008th author: Shishir, Tushar Ahmed title: In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date: 2020-08-16 words: 2974.0 sentences: 171.0 pages: flesch: 54.0 cache: ./cache/cord-254636-3lr008th.txt txt: ./txt/cord-254636-3lr008th.txt summary: We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. We conducted comparative analysis of publicly available genome sequences of SARS-CoV-2 from 27 countries to predict the origin of viruses in Bangladesh by studying a time-4 resolved phylogenetic relationship. Later, we analyzed the variants present in different isolates of Bangladesh to understand the pattern of mutations in relation to the ancestral Wuhan strain, find unique mutations, and possible effect of these mutations on the stability of encoded proteins, and selection pressure on genes. abstract: The COVID19 pandemic caused by SARS-CoV-2 virus has severely affected most countries of the world including Bangladesh. We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Phylogenetic analysis indicated that the pathogen was imported in Bangladesh from multiple countries. The viruses found in the southern district of Chattogram were closely related to strains from Saudi Arabia whereas those in Dhaka were similar to that of United Kingdom and France. The 64 SARS-CoV-2 sequences from Bangladesh belonged to three clusters. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. Among these, 99 missense mutations (90%) were predicted to destabilize protein structures. Remarkably, a mutation that leads to an I300F change in the nsp2 protein and a mutation leading to D614G change in the spike protein were prevalent in SARS-CoV-2 genomic sequences, and might have influenced the epidemiological properties of the virus in Bangladesh. url: https://doi.org/10.1101/2020.07.20.212563 doi: 10.1101/2020.07.20.212563 id: cord-308342-ycdok8fc author: Shutler, J. title: Risk of SARS-CoV-2 infection from contaminated water systems date: 2020-06-20 words: 3147.0 sentences: 196.0 pages: flesch: 57.0 cache: ./cache/cord-308342-ycdok8fc.txt txt: ./txt/cord-308342-ycdok8fc.txt summary: Collectively this evidence suggests that SARS-CoV-2 virus can survive 45 within water and the viral loads within untreated sewage effluent are likely high in countries 46 of high infection rates, a portion of which is viable virus, and therefore water contaminated 47 We note that adenoviruses are 122 known to be particularly resilient, and therefore likely to represent an upper estimate, but 123 also that our selected range is consistent with the 10 -3 value used elsewhere for assessing 124 viral risk in water systems (eg 14 ), including one assessment for SARS CoV-2 transmission 125 risk to wastewater workers 18 . Collectively this means that if a drinking water source 156 was to become infected with SARS-CoV-2 the standard virus removal and disinfection 157 approaches of ultraviolet exposure and chlorination may not reduce the virus below 158 detectable limits. abstract: Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed. url: http://medrxiv.org/cgi/content/short/2020.06.17.20133504v1?rss=1 doi: 10.1101/2020.06.17.20133504 id: cord-339344-qd73h1ie author: Simon, David title: Patients with immune-mediated inflammatory diseases receiving cytokine inhibitors have low prevalence of SARS-CoV-2 seroconversion date: 2020-07-24 words: 4094.0 sentences: 202.0 pages: flesch: 43.0 cache: ./cache/cord-339344-qd73h1ie.txt txt: ./txt/cord-339344-qd73h1ie.txt summary: To test whether differences in social exposure between the groups account for the low prevalence of SARS-CoV-2 IgG responses in IMID patients treated with cytokine inhibitors, we assessed exposure risk variables (contact with persons with a respiratory infection, presence at workplace outside home, travel to risk areas) of IMID patient groups and control groups. The low seroprevalence of SARS-CoV-2 in anti-cytokine treated IMIDs could have two principle explanations: While (i) the four groups were recruited in the same region, (ii) the HC control group having the highest prevalence for SARS-CoV-2 IgG was in direct contact with the IMID patients and (iii) all participants were exposed to similar detailed information regarding social behavior during the outbreak of the COVID-19 pandemic in Germany, IMID patients may have followed an even more stringent exposure prophylaxis than healthy individuals. abstract: Immune-mediated inflammatory diseases (IMIDs) of the joints, gut and skin are treated with inhibitors of inflammatory cytokines. These cytokines are involved in the pathogenesis of coronavirus disease 2019 (COVID-19). Investigating anti-SARS-CoV-2 antibody responses in IMIDs we observe a reduced incidence of SARS-CoV-2 seroconversion in IMID patients treated with cytokine inhibitors compared to patients receiving no such inhibitors and two healthy control populations, despite similar social exposure. Hence, cytokine inhibitors seem to at least partially protect from SARS-CoV-2 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32709909/ doi: 10.1038/s41467-020-17703-6 id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 words: 5978.0 sentences: 304.0 pages: flesch: 49.0 cache: ./cache/cord-290290-wyx9ib7s.txt txt: ./txt/cord-290290-wyx9ib7s.txt summary: title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. abstract: The spike (S) protein is one of the three proteins forming the coronaviruses’ viral envelope. The S protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has a spatial structure similar to the S proteins of other mammalian coronaviruses, except for a unique receptor-binding domain (RBD), which is a significant inducer of host immune response. Recombinant SARS-CoV-2 RBD is widely used as a highly specific minimal antigen for serological tests. Correct exposure of antigenic determinants has a significant impact on the accuracy of such tests – the antigen has to be correctly folded, contain no potentially antigenic non-vertebrate glycans, and, preferably, should have a glycosylation pattern similar to the native S protein. Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. RBDv1 contained a native viral signal peptide, RBDv2 – human tPA signal peptide. We transfected a CHO DG44 cell line, selected stably transfected cells, and performed a few rounds of methotrexate-driven amplification of the genetic cassette in the genome. For the RBDv2 variant, a high-yield clonal producer cell line was obtained. We developed a simple purification scheme that consistently yielded up to 30 mg of RBD protein per liter of the simple shake flask cell culture. Purified proteins were analyzed by polyacrylamide gel electrophoresis in reducing and non-reducing conditions and gel filtration; for RBDv2 protein, the monomeric form content exceeded 90% for several series. Deglycosylation with PNGase F and mass spectrometry confirmed the presence of N-glycosylation. The antigen produced by the described technique is suitable for serological tests and similar applications. url: https://doi.org/10.1101/2020.11.04.368092 doi: 10.1101/2020.11.04.368092 id: cord-319241-div9rzax author: Singh, Bhuchitra title: Severe Acute Respiratory Syndrome‐Corona Virus‐2 (SARS‐CoV‐2) and its Effect on Gametogenesis and Early Pregnancy date: 2020-09-23 words: 4386.0 sentences: 305.0 pages: flesch: 50.0 cache: ./cache/cord-319241-div9rzax.txt txt: ./txt/cord-319241-div9rzax.txt summary: There is also evidence of significant placental pathology in SARS‐CoV‐2 infection, but it is unclear what effects there may be for early pregnancy, though available data suggest less severe effects compared to other respiratory virus outbreaks. We searched for articles that contained information related to SARS-CoV-2 and reproductive tissues (ovaries, testes), gametes, placentation, and early pregnancy in humans. Our search phrases included: "severe acute respiratory syndrome coronavirus 2", "2019 ncov", "sarscov 2", "SARS-Cov-2", "pregnancy", "gravidity", "abortion", "germ cells", "oocytes", "gametes", "embryonic structures", "embryo", "fertility", "testes", "miscarriage"(See Appendix 1 for completed list of databases search strategy and Figure 1 for PRISMA table). Specifically, 10 women with severe COVID-19 were tested or SARS-CoV-2 in vaginal fluid, with all samples negative for virus [48] . Another study performed during the 2002-2003 SARS pandemic showed that 4 of 7 (57%) pregnant women infected with SARS-CoV had a spontaneous miscarriage in the first trimester of pregnancy [55] , though notably no viral inclusion bodies or particles were detected in the products of conception. abstract: SARS‐CoV‐2 infection and pregnancy has been the topic of hundreds of publications over the last several months, however, few studies have focused on the implications of infection in early pregnancy and reproductive tissues. Here we analyzed available evidence pertaining to SARS‐CoV‐2 infection, early pregnancy, and reproductive tissues. We searched PubMed and Embase databases in accordance with guidelines of Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) for publications from inception to June 4, 2020. Four reviewers screened titles and abstracts, and obtained full text articles for analysis. 62 studies were included in the review. Biological plausibility for infection with SARS‐CoV‐2 exists in testis, ovaries, and placenta as they express ACE2 receptor activity. In males, SARS‐CoV‐2 infection could lead to functional abnormalities leading to spermatogenic failure and male infertility. In females, an alteration of the ACE2 cascade via SARS‐CoV‐2 infection could lead to impairment in important follicular and luteal processes. There is also evidence of significant placental pathology in SARS‐CoV‐2 infection, but it is unclear what effects there may be for early pregnancy, though available data suggest less severe effects compared to other respiratory virus outbreaks. Further investigation is needed regarding SARS‐CoV‐2 in reproductive function and early pregnancy. url: https://www.ncbi.nlm.nih.gov/pubmed/32969123/ doi: 10.1111/aji.13351 id: cord-268476-3lxsh1zz author: Skoog, Hunter title: Tracheotomy in the SARS‐CoV‐2 pandemic date: 2020-04-29 words: 1504.0 sentences: 91.0 pages: flesch: 44.0 cache: ./cache/cord-268476-3lxsh1zz.txt txt: ./txt/cord-268476-3lxsh1zz.txt summary: The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. The severe acute respiratory syndrome (SARS)-CoV-2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. Our priorities in establishing these guidelines included: optimal patient care, protection of medical personnel, minimizing further spread of the virus and preservation of important resources (ICU beds, ventilators, and PPE). Due to the paucity of data regarding the current SARS-CoV-2 epidemic, the literature from the SARS epidemic of In Canada, 43% of cases occurred in health care workers as a result of AGPs. 1,2 One instance involved a difficult intubation of a patient who was under investigation for SARS. There are multiple reports 3,4 of safely performing tracheotomy on patients with SARS without infecting health care workers. abstract: The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. As such, surgeons will be called upon to perform tracheotomy for a subset of these chronically intubated patients. As seen during the SARS and the SARS‐CoV‐2 outbreaks, aerosol‐generating procedures (AGP) have been associated with higher rates of infection of medical personnel and potential acceleration of viral dissemination throughout the medical center. Therefore, a thoughtful approach to tracheotomy (and other AGPs) is imperative and maintaining traditional management norms may be unsuitable or even potentially harmful. We sought to review the existing evidence informing best practices and then develop straightforward guidelines for tracheotomy during the SARS‐CoV‐2 pandemic. This communication is the product of those efforts and is based on national and international experience with the current SARS‐CoV‐2 pandemic and the SARS epidemic of 2002/2003. url: https://www.ncbi.nlm.nih.gov/pubmed/32342565/ doi: 10.1002/hed.26214 id: cord-029112-u507i0t0 author: Smith, Keisha title: A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study protocol for a randomised controlled trial date: 2020-07-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVES: Primary Objective • To evaluate the effect of ravulizumab, a long-acting complement (C5) inhibitor plus best supportive care (BSC) compared with BSC alone on the survival of patients with COVID-19. Secondary Objectives • Number of days free of mechanical ventilation at Day 29 • Duration of intensive care unit stay at Day 29 • Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 29 • Change from baseline in peripheral capillary oxygen saturation/ fraction of inspired oxygen (SpO2 /FiO2) at Day 29 • Duration of hospitalization at Day 29 • Survival (based on all-cause mortality) at Day 60 and Day 90 Safety • Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events. PK/PD/Immunogenicity • Change in serum ravulizumab concentrations over time • Change in serum free and total C5 concentrations over time • Incidence and titer of anti-ALXN1210 antibodies Biomarkers • Change in absolute level of soluble biomarkers in blood associated with complement activation, inflammatory processes, and hypercoagulable states over time Exploratory • Incidence of progression to renal failure requiring dialysis at Day 29 • Time to clinical improvement (based on a modified 6-point ordinal scale) over 29 days • SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores at Day 29 (or discharge), Day 60, and Day 90 • EuroQol 5-dimension 5-level (EQ-5D-5L) scores at Day 29 (or discharge), Day 60, and Day 90 TRIAL DESIGN: This is a multicenter Phase 3, open-label, randomized, controlled, study. The study is being conducted in acute care hospital settings in the United States, United Kingdom, Spain, France, Germany, and Japan. PARTICIPANTS: Male or female patients at least 18 years of age, weighing ≥ 40 kg, admitted to a designated hospital facility for treatment will be screened for eligibility in this study. Key Inclusion criteria • Confirmed diagnosis of SARS-CoV-2 infection (eg, via polymerase chain reaction [PCR] and/or antibody test) presenting as severe COVID-19 requiring hospitalization • Severe pneumonia, acute lung injury, or ARDS confirmed by computed tomography (CT) or X-ray at Screening or within the 3 days prior to Screening, as part of the patient’s routine clinical care • Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or non-invasive (with continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) Key Exclusion criteria • Patient is not expected to survive for more than 24 hours • Patient is on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening • Severe pre-existing cardiac disease (ie, NYHA Class 3 or Class 4, acute coronary syndrome, or persistent ventricular tachyarrhythmias) • Patient has an unresolved Neisseria meningitidis infection Excluded medications and therapies • Current treatment with a complement inhibitor • Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on Day 1 Excluded prior/concurrent clinical study experience • Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever is greater • Exceptions a. Investigational therapies will be allowed if received as part of best supportive care through an expanded access protocol or emergency approval for the treatment of COVID-19. b. Investigational antiviral therapies (such as remdesivir) will be allowed even if received as part of a clinical study. INTERVENTION AND COMPARATOR: The study consists of a Screening Period of up to 3 days, a Primary Evaluation Period of 4 weeks, a final assessment at Day 29, and a Follow-up Period of 8 weeks. For patients randomized to ravulizumab plus BSC, a weight-based dose of ravulizumab (≥40 to < 60 kg/2400 mg, 60 to < 100 kg/2700 mg, ≥ 100 kg/3000 mg) will be administered on Day 1. On Day 5 and Day 10, additional doses of 600 mg (≥40 to <60 kg) or 900 mg (>60 kg) ravulizumab will be administered and on Day 15 patients will receive 900 mg ravulizumab. There is no active or placebo comparator in this open-label clinical trial. The total duration of each patient’s participation is anticipated to be approximately 3 months. MAIN OUTCOMES: The primary efficacy outcome of this study is survival (based on all-cause mortality) at Day 29. RANDOMISATION: Patients will be randomized in a 2:1 ratio (ravulizumab plus BSC:BSC alone). Randomization will be stratified by intubated or not intubated on Day 1. Computer-generated randomization lists will be prepared by a third party under the direction of the sponsor. Investigators, or designees, will enrol patients and then obtain randomization codes using an interactive voice/web response system. The block size will be kept concealed so that investigators cannot select patients for a particular treatment assignment. Blinding (masking): This is an open-label study. Numbers to be randomised (sample size): Approximately 270 patients will be randomly assigned in a 2:1 ratio to ravulizumab plus BSC (n=180) or BSC alone (n=90). TRIAL STATUS: Protocol Number: ALXN1210-COV-305 Original Protocol: 09 Apr 2020 Protocol Amendment 1 (Global): 13 Apr 2020 Protocol Amendment 2 (Global): 17 Apr 2020 Protocol Amendment 3 (Global): 09 Jun 2020 Recruitment is currently ongoing. Recruitment was initiated on 11 May 2020. We expect recruitment to be completed by 30 Nov 2020. TRIAL REGISTRATION: Clinicaltrials.gov: Protocol Registry Number: NCT04369469; First posted; 30 Apr 2020 EU Clinical Trials Register: EudraCT Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=ALXN1210-COV-305, Start date: 07 May 2020 FULL PROTOCOL: The full redacted protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355517/ doi: 10.1186/s13063-020-04548-z id: cord-033780-184e64tr author: Smith, Rasheid title: Implications of current and future approaches to coronavirus disease 2019 testing date: 2020-10-13 words: 3266.0 sentences: 154.0 pages: flesch: 44.0 cache: ./cache/cord-033780-184e64tr.txt txt: ./txt/cord-033780-184e64tr.txt summary: The current reality is that SARS-CoV-2 is a highly transmissible airborne disease with a broad presentation of symptoms and leaves lasting damage in severe cases, and for which there is a scarcity of effective medications to treat it. Using the cycle threshold value in this manner only informs as to the presence of the virus and may not reveal disease progression, severity and viral load in the sample; and as such the results are largely qualitative despite the inherent quantitative nature of real-time RT-PCR [27] . Nevertheless, initial studies have demonstrated that chest CT imaging is more accurate than RT-PCR at detecting SARS-CoV-2 patients [32] with 97.2% versus 83% in the early stages of infection [33] . Immunoassays (antibody serum tests), such as enzyme-linked immunosorbent assays (ELISAs), are used to detect the presence of serum antibodies (either IgA, IgG or IgM) to viral proteins and can indicate when a person has developed an immune response to SARS-CoV-2. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560716/ doi: 10.2217/fvl-2020-0318 id: cord-341287-i1hyk962 author: Smith, Trevor R. F. title: Immunogenicity of a DNA vaccine candidate for COVID-19 date: 2020-05-20 words: 7803.0 sentences: 446.0 pages: flesch: 54.0 cache: ./cache/cord-341287-i1hyk962.txt txt: ./txt/cord-341287-i1hyk962.txt summary: Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. In subjects immunized with INO-4700 (MERS-CoV S protein DNA vaccine) durable neutralizing antibodies (nAbs) and T cell immune responses were measured, and a seroconversion rate of 96% was observed and immunity was followed for 60 weeks in most study volunteers 9 . We followed the induction of immunity by the selected immunogen in mice and guinea pigs, measuring SARS-CoV-2 S protein-specific antibody levels in serum and in the lung fluid, and antibody functionality through competitive inhibition of ACE2 binding, pseudovirus and live virus neutralization. In summary, humoral immunogenicity testing in both mice and guinea pigs revealed the COVID-19 vaccine candidate, INO-4800, was capable of eliciting functional blocking antibody responses to SARS-CoV-2 spike protein. abstract: The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study. url: https://www.ncbi.nlm.nih.gov/pubmed/32433465/ doi: 10.1038/s41467-020-16505-0 id: cord-262045-r2iqpmmc author: Smits, Saskia L. title: Reliable typing of MERS-CoV variants with a small genome fragment date: 2014-12-15 words: 2151.0 sentences: 110.0 pages: flesch: 49.0 cache: ./cache/cord-262045-r2iqpmmc.txt txt: ./txt/cord-262045-r2iqpmmc.txt summary: RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. In addition, the MERS-CoV variant typing assay was performed on camel samples from a slaughterhouse in Qatar [13] and sequences for 14 MERS-CoV positive animals with cycle threshold values ranging from 12.9 to 32.2 as determined by UpE real time RT-PCR [17, 18] were obtained (Fig. 2) . Subsequent analyses revealed a region in the open reading frame that encodes the spike protein with a number of positions in which nucleotide variation occurs between MERS-CoV variants with a strong phylogenetic signal regarding previously identified clusters of viruses based on full-length MERS-CoV genomes. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia abstract: BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes lower respiratory tract infection in humans. Camels are the likely animal source for zoonotic infection, although exact transmission modes remain to be determined. Human-to-human transmission occurs sporadically. The wide geographic distribution of MERS-CoV among dromedary camels and ongoing transmissions to humans provides concern for the evolution of a MERS-CoV variant with efficient human-to-human transmission capabilities. Phylogenetic analysis of MERS-CoV has occurred by analysis of full-length genomes or multiple concatenated genome fragments, which is time-consuming, costly and limited to high viral load samples. OBJECTIVE: To develop a simple, reliable MERS-CoV variant typing assay to facilitate monitoring of MERS-CoV diversity in animals and humans. STUDY DESIGN: Phylogenetic analysis of presently known full-length MERS-CoV genomes was performed to identify genomic regions with sufficient phylogenetic content to allow reliable MERS-CoV variant typing. RT-PCR assays targeting these regions were designed and optimized. RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. The detection limit corresponds to a cycle treshold value of ∼35 with standard upE real time PCR assays on RNA isolated from MERS-CoV EMC. Nasal swabs from RT-PCR positive camels (Ct values 12.9–32.2) yielded reliable sequence information in 14 samples. CONCLUSIONS: We developed a simple, reliable MERS-CoV variant typing assay which is crucial in monitoring MERS-CoV circulation in real time with relatively little investment on location. url: https://www.sciencedirect.com/science/article/pii/S1386653214004685 doi: 10.1016/j.jcv.2014.12.006 id: cord-259603-bh198xgl author: Snijder, E.J. title: The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing date: 2016-09-14 words: 24187.0 sentences: 1090.0 pages: flesch: 50.0 cache: ./cache/cord-259603-bh198xgl.txt txt: ./txt/cord-259603-bh198xgl.txt summary: Reverse-genetics studies targeting specific residues in SARS-CoV nsp7 confirmed the protein''s importance for virus replication (Subissi et al., 2014b) , although the impact of single point mutations was smaller than anticipated on the basis of the biochemical characterization of the RNA-binding properties of nsp7-containing protein complexes in vitro (see later). The large number of viral subunits in these complexes (Subissi et al., 2014a) , the likely requirement for host factors (van Hemert et al., 2008) , and the concept of RNA synthesis occurring in a dedicated microenvironment in the infected cell (Knoops et al., 2008; V''Kovski et al., 2015) complicate the straightforward characterization of the CoV RdRp. To reconstitute the enzyme''s activities in vitro, purified recombinant nsp12 is a key reagent but, for many years, such studies were hampered by poor nsp12 expression in Escherichia coli. abstract: Coronaviruses are animal and human pathogens that can cause lethal zoonotic infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes and belong to the order Nidovirales, a diverse group of viruses for which common ancestry was inferred from the common principles underlying their genome organization and expression, and from the conservation of an array of core replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes (~ 26–32 kilobases) are the largest RNA genomes known to date and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases. The primary functions that direct coronavirus RNA synthesis and processing reside in nonstructural protein (nsp) 7 to nsp16, which are cleavage products of two large replicase polyproteins translated from the coronavirus genome. Significant progress has now been made regarding their structural and functional characterization, stimulated by technical advances like improved methods for bioinformatics and structural biology, in vitro enzyme characterization, and site-directed mutagenesis of coronavirus genomes. Coronavirus replicase functions include more or less universal activities of plus-stranded RNA viruses, like an RNA polymerase (nsp12) and helicase (nsp13), but also a number of rare or even unique domains involved in mRNA capping (nsp14, nsp16) and fidelity control (nsp14). Several smaller subunits (nsp7–nsp10) act as crucial cofactors of these enzymes and contribute to the emerging “nsp interactome.” Understanding the structure, function, and interactions of the RNA-synthesizing machinery of coronaviruses will be key to rationalizing their evolutionary success and the development of improved control strategies. url: https://api.elsevier.com/content/article/pii/S0065352716300471 doi: 10.1016/bs.aivir.2016.08.008 id: cord-350903-nwagvvc5 author: Softic, Laurent title: Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025) date: 2020-06-23 words: 1398.0 sentences: 80.0 pages: flesch: 47.0 cache: ./cache/cord-350903-nwagvvc5.txt txt: ./txt/cord-350903-nwagvvc5.txt summary: Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC(50)) of 0.46 ± 0.04 μM. For instance, chloroquine has been shown to bear potent antiviral properties against SARS-CoV-2 in vitro, and several clinical trials are under way to assess its efficacy in patients with COVID-19. Cyclosporine A (CsA), a potent cyclophilin inhibitor, blocks the replication of various coronaviruses in vitro, including HCoV-229E, HCoV-NL63, FPIV, mouse hepatitis virus (MHV), avian infectious bronchitis virus, and SARS-CoV (5, (8) (9) (10) . The antiviral effectiveness of increasing concentrations of alisporivir was measured in Vero E6 cells infected with a clinical isolate of SARS-CoV-2 at a multiplicity of infection (MOI) of 0.02 (Fig. 1A) . These results justify rapidly conducting a proof-of-concept phase 2 trial to assess the antiviral properties and the effect of alisporivir on COVID-19 clinical outcomes in infected patients. abstract: Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC(50)) of 0.46 ± 0.04 μM. Alisporivir inhibited a postentry step of the SARS-CoV-2 life cycle. These results justify rapidly conducting a proof-of-concept phase 2 trial with alisporivir in patients with SARS-CoV-2 infection. url: https://doi.org/10.1128/aac.00876-20 doi: 10.1128/aac.00876-20 id: cord-338544-eph89g47 author: Spuntarelli, Valerio title: COVID-19: is it just a lung disease? A case-based review date: 2020-07-28 words: 2279.0 sentences: 142.0 pages: flesch: 44.0 cache: ./cache/cord-338544-eph89g47.txt txt: ./txt/cord-338544-eph89g47.txt summary: COVID-19 pandemic reached 3.78 million confirmed reported cases worldwide, and it is generally associated to the acronym that precedes its name: severe acute respiratory syndrome (SARS). A prospective study investigating left ventricular performance in 46 patients with severe acute respiratory syndrome showed subclinical diastolic impairment without systolic involvement [3] . Pathological findings of COVID-19 associated with acute respiratory distress syndrome showed few interstitial mononuclear inflammatory infiltrates, but no other substantial damage in the heart tissue [7] . A case report highlights myocarditis as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia in an otherwise healthy 53-year-old white woman [8] . The authors concluded that the presence of the characteristic features of symmetric, multifocal lesions with thalamic involvement suggests that this is a case of acute necrotizing hemorrhagic encephalopathy associated with COVID-19. Guillain Barre syndrome associated with COVID-19 infection: a case report abstract: Due to its extreme virulence, COVID-19 virus has rapidly spread, developing a severe pandemic. SARS-COV-2 mostly affected the respiratory tract, causing a severe acute lung failure. Although the infection of airways, COVID-19 can be associated with chronic and systemic damages still not so much known. The purpose of this research is to collect recent evidence in literature about systemic diseases caused by COVID-19. The format of the present article has features of a systematic case-based review (level of evidence), and it is structured as a case series report (patients of our COVID-19 Medicine Ward have been selected as cases). Data for this review have been selected systematically, taking evidence only from indexed journals and databases: PubMed, Scopus, MEDLINE, and Cochrane systems. Papers chosen included systematic reviews, case series, clinical cases, meta-analysis studies, and RCTs. We start collecting studies since 2003. The main keywords used were “COVID-19” “OR” “SARS” “OR” “SARS – COV 2” “AND” “systemic disease” / “nephropathy” / “cardiac pathology” / “central nervous system.” Clinical cases belong to our COVID-19 Medicine Ward. One of the most severe COVID-19 clinical presentations includes cardiovascular problems, like myocarditis, pericarditis, and acute hearth failure. Cytokine release syndrome caused by COVID-19 develops severe acute kidney failure. It is still unknown the way coronavirus damages the liver, brain, and reproductive system. Considering the majority of the new studies about this pathology, it issues that COVID-19 is considered to be a multi-organ disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32838177/ doi: 10.1007/s42399-020-00418-6 id: cord-331429-mh2hd5fe author: Srikantiah, Padmini title: SARS Clinical Features, United States, 2003 date: 2005-01-17 words: 1948.0 sentences: 100.0 pages: flesch: 48.0 cache: ./cache/cord-331429-mh2hd5fe.txt txt: ./txt/cord-331429-mh2hd5fe.txt summary: We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection. Case-patients with laboratory-confirmed SARS were compared to a convenience sample of persons who met the clinical and epidemiologic criteria for suspected or probable SARS but subsequently tested negative for SARS-CoV infection. Controls had negative findings on all testing performed for SARS-CoV, including the absence of antibody against the virus in convalescent-phase serum samples obtained >21 days after onset of symptoms. Over the course of their illness, findings suggestive of a lower respiratory tract infection developed in all 8 patients with laboratory-confirmed SARS; these findings included dyspnea (n = 8), rales (n = 5), and hypoxia (n = 5) (Table 1) . abstract: We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/15705339/ doi: 10.3201/eid1101.040585 id: cord-329493-ueqlhgn0 author: Stadler, Konrad title: SARS — beginning to understand a new virus date: 2003 words: 5146.0 sentences: 248.0 pages: flesch: 51.0 cache: ./cache/cord-329493-ueqlhgn0.txt txt: ./txt/cord-329493-ueqlhgn0.txt summary: A new infectious disease, known as severe acute respiratory syndrome (SARS), appeared in the Guangdong province of southern China in 2002. When Thiel and colleagues 20 isolated one genomic and eight subgenomic RNAs from the FRA strain and sequenced their 5′ ends, they identified a conserved sequence (5′ACGAAC3′) that was located in coronaviruses: S, spike protein; E, envelope protein; M, membrane glycoprotein; and N, nucleocapsid protein. Alternatively, these antigens could be delivered by DNA immunization by Figure 6 | The S1 domain of SARS-CoV spike is structurally related to group 2 coronaviruses. Schematic representation of cysteine positions in the S1 domains of group 1, 2 and 3 coronaviruses, compared with the SARS-CoV spike protein. The complete genome sequence of a SARS-CoV isolate (FRA) and experimental data on its key RNA elements and protein functions are described. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection abstract: The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again. url: https://www.ncbi.nlm.nih.gov/pubmed/15035025/ doi: 10.1038/nrmicro775 id: cord-303741-1ou0cy5k author: Stafstrom, Carl E. title: COVID-19: Neurological Considerations in Neonates and Children date: 2020-09-10 words: 7035.0 sentences: 369.0 pages: flesch: 40.0 cache: ./cache/cord-303741-1ou0cy5k.txt txt: ./txt/cord-303741-1ou0cy5k.txt summary: An especially apropos case demonstrated maternal viremia, placental infection shown by immunohistochemistry, and high placental viral load with subsequent neonatal viremia, implying transplacental transfer of SARS-CoV-2 from pregnant mother to fetus [24] ; this newborn presented with neurological symptoms as discussed in Section 3. The lack of unequivocal reports of SARS-CoV-2 being recovered from the CSF of individuals affected with presumed neurological involvement nor in brain tissue from the limited number of autopsied cases strengthens the possibility that the virus does not often directly cause the symptoms but rather, that the neurological sequelae are secondary to hypoxia, cytokine involvement, or some other non-direct mechanism (see Section 6). Finally, 4 of 27 children with COVID-19 associated MIS-C developed new neurologic symptoms including encephalopathy, headache, weakness, ataxia, and dysarthria [81] ; two patients had lumbar punctures and CSF was negative for SARS-CoV-2 in both. abstract: The ongoing worldwide pandemic of the novel human coronavirus SARS-CoV-2 and the ensuing disease, COVID-19, has presented enormous and unprecedented challenges for all medical specialists. However, to date, children, especially neonates, have been relatively spared from the devastating consequences of this infection. Neurologic involvement is being increasingly recognized among adults with COVID-19, who can develop sensory deficits in smell and taste, delirium, encephalopathy, headaches, strokes, and peripheral nervous system disorders. Among neonates and children, COVID-19-associated neurological manifestations have been relatively rare, yet reports involving neurologic dysfunction in this age range are increasing. As discussed in this review, pediatric neurologists and other pediatric specialists should be alert to potential neurological involvement by this virus, which might have neuroinvasive capability and carry long-term neuropsychiatric and medical consequences. url: https://www.ncbi.nlm.nih.gov/pubmed/32927628/ doi: 10.3390/children7090133 id: cord-275690-83nrzfon author: Stanifer, Megan L. title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 words: 4696.0 sentences: 256.0 pages: flesch: 52.0 cache: ./cache/cord-275690-83nrzfon.txt txt: ./txt/cord-275690-83nrzfon.txt summary: title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, and in agreement with the results observed in cells depleted of the type III IFN receptor, this increase in infectivity was also associated with an increase in infectious denovo virus particle production ( Fig. 3G ). All together, these results strongly support a model where the type III IFN mediated signaling controls SARS-CoV-2 infection in human intestinal epithelial cells. All together these results show that human colon organoids can support SARS-CoV-2 infection, replication and spread and that the type III IFN response plays a critical role in controlling virus replication. abstract: SARS-CoV-2 is an unprecedented worldwide health problem that requires concerted and global approaches to better understand the virus in order to develop novel therapeutic approaches to stop the COVID-19 pandemic and to better prepare against potential future emergence of novel pandemic viruses. Although SARS-CoV-2 primarily targets cells of the lung epithelium causing respiratory infection and pathologies, there is growing evidence that the intestinal epithelium is also infected. However, the importance of the enteric phase of SARS-CoV-2 for virus-induced pathologies, spreading and prognosis remains unknown. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of SARS-CoV-2 lifecycle in human intestinal epithelial cells. Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, we identified intestinal epithelial cells as the best culture model to propagate SARS-CoV-2. We found that viral infection elicited an extremely robust intrinsic immune response where, interestingly, type III interferon mediated response was significantly more efficient at controlling SARS-CoV-2 replication and spread compared to type I interferon. Taken together, our data demonstrate that human intestinal epithelial cells are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing in increasing patient viremia and by fueling an exacerbated cytokine response. url: https://doi.org/10.1101/2020.04.24.059667 doi: 10.1101/2020.04.24.059667 id: cord-290796-x9xqqcj6 author: Stefanelli, P. title: Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento date: 2020-11-13 words: 3142.0 sentences: 212.0 pages: flesch: 55.0 cache: ./cache/cord-290796-x9xqqcj6.txt txt: ./txt/cord-290796-x9xqqcj6.txt summary: All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. The duration of protection against infection with common human coronaviruses appears to be rather short 2, 3 , and there are studies showing declines in IgG antibodies against SARS-CoV-2 among both symptomatic and asymptomatic individuals 4, 5 . In order to evaluate the persistence of SARS-CoV-2 antibodies, we repeated a serosurvey in five municipalities of the Autonomous Province (AP) of Trento, Italy, recruiting those individuals who had resulted positive in a large population-based seroprevalence study conducted 4 months before 14 . The analyser automatically calculates SARS-CoV-2 NC IgG antibody concentration expressed as an is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint abstract: Background. There are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before. Methods. All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID50) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA). Findings. Overall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity. Interpretation. A decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity. url: https://doi.org/10.1101/2020.11.11.20229062 doi: 10.1101/2020.11.11.20229062 id: cord-353209-qkhfp66l author: Steiner, Daniel J. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 words: 2517.0 sentences: 129.0 pages: flesch: 45.0 cache: ./cache/cord-353209-qkhfp66l.txt txt: ./txt/cord-353209-qkhfp66l.txt summary: We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. Aminereactive substrates for fabrication of AIR arrays were provided by Adarza BioSystems, Inc. For ELISA assays, SARS-CoV-2 full-length spike and RBD were produced in-house using a mammalian expression system, 20,21 as was influenza A/H1N1/California 2009 hemagglutinin. To that end, we have presented preliminary data on a 15-plex array on the AIR platform, developed in response to the need to study SARS-CoV-2 but incorporating antigens for other coronaviruses and influenza. Responses to SARS-CoV-2 antigens on the array effectively discriminated between serum samples from uninfected and COVID-19 convalescent subjects, with generally good correlation to ELISA data. abstract: Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses. url: https://doi.org/10.1101/2020.06.15.153064 doi: 10.1101/2020.06.15.153064 id: cord-342796-f7n8sxbu author: Stowe, J. title: Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design date: 2020-09-18 words: 3923.0 sentences: 218.0 pages: flesch: 48.0 cache: ./cache/cord-342796-f7n8sxbu.txt txt: ./txt/cord-342796-f7n8sxbu.txt summary: Findings: The risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Severity and risk of death among individuals with a coinfection: The mortality rate among individuals with a SARS-CoV-2 and influenza coinfection and those with SARS-CoV-2 infection who tested negative for influenza was calculated by dividing the number of deaths by the total number of individuals tested by age group. We also found strong evidence that coinfection with influenza and SARS-CoV-2 was associated with an increased risk of death or severe disease and that this appears to be beyond the additive effect of the two viruses acting independently. abstract: Background: The potential impact of COVID-19 alongside influenza on morbidity, mortality and health service capacity is a major concern as the Northern Hemisphere winter approaches. This study investigates the interaction between influenza and COVID-19 during the latter part of the 2019-20 influenza season in England. Methods: Individuals tested for influenza and SARS-CoV-2 were extracted from national surveillance systems between 20/01/2020 and 25/04/2020. To estimate influenza infection on the risk of SARS-CoV-2 infection, univariable and multivariable analyses on the odds of SARS-CoV-2 in those who tested positive for influenza compared to those who tested negative for influenza. To assess whether a coinfection was associated with severe SARS-CoV-2 outcome, univariable and multivariable analyses on the odds of death adjusted for age, sex, ethnicity, comorbidity and coinfection status. Findings: The risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. Patients with a coinfection had a risk of death of 5.92 (95% CI, 3.21-10.91) times greater than among those with neither influenza nor SARS-CoV-2 suggesting possible synergistic effects in coinfected individuals. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Interpretation: Cocirculation of these viruses could have a significant impact on morbidity, mortality and health service demand. Testing for influenza alongside SARS-CoV-2 and maximising influenza vaccine uptake should be prioritised to mitigate these risks. url: http://medrxiv.org/cgi/content/short/2020.09.18.20189647v1?rss=1 doi: 10.1101/2020.09.18.20189647 id: cord-266348-tbr2ynx0 author: Stroemer, A. title: Diagnostic accuracy of six commercial SARS-CoV-2 IgG/total antibody assays and identification of SARS-CoV-2 neutralizing antibodies in convalescent sera date: 2020-06-17 words: 2893.0 sentences: 215.0 pages: flesch: 61.0 cache: ./cache/cord-266348-tbr2ynx0.txt txt: ./txt/cord-266348-tbr2ynx0.txt summary: Here, we compare the diagnostic accuracy of six commercially available SARS-CoV-2 IgG (Abbott SARS-CoV-2 IgG; Diasorin Liaison SARS-CoV-2 S1/2 IgG; Epitope EDI Novel Coronavirus COVID-19 IgG ELISA Kit; Euroimmun Anti-SARS-CoV-2 ELISA (IgG); Mikrogen recomWell SARS-CoV-2 IgG) or total SARS-CoV-2 antibody assays (Roche Elecsys Anti-SARS-CoV-2). The majority of assay results were confirmed in a laboratory-developed plaque reduction neutralization test and by a SARS-CoV-2 IgG-specific line assay including measurement of generally low IgG avidities (Mikrogen recomLine Coronavirus IgG [Aviditaet], prototype). Out 132 of the remaining 34 samples, only one serum (#20; Figure 1 ) which was obtained ten days after a positive 133 RT-PCR was tested negative for SARS-CoV-2 IgG/total antibodies in the six assays. Six of them -including three family members of a 153 confirmed COVID-19 case (#22; Figure 1 ) -were classified SARS-CoV-2 IgG/total antibody positive by the 154 majority of the tests. abstract: The reliable detection of immunoglobulin G (IgG) or total antibodies directed against the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is important for clinical diagnostics and epidemiological studies. Here, we compare the diagnostic accuracy of six commercially available SARS-CoV-2 IgG (Abbott SARS-CoV-2 IgG; Diasorin Liaison SARS-CoV-2 S1/2 IgG; Epitope EDI Novel Coronavirus COVID-19 IgG ELISA Kit; Euroimmun Anti-SARS-CoV-2 ELISA (IgG); Mikrogen recomWell SARS-CoV-2 IgG) or total SARS-CoV-2 antibody assays (Roche Elecsys Anti-SARS-CoV-2). The test sensitivities were analyzed with a set of 34 sera obtained from 26 patients after PCR-confirmed SARS-CoV-2 infection and varied from 76.9% (Euroimmun) to 96.2% (Abbott). The majority of assay results were confirmed in a laboratory-developed plaque reduction neutralization test and by a SARS-CoV-2 IgG-specific line assay including measurement of generally low IgG avidities (Mikrogen recomLine Coronavirus IgG [Aviditaet], prototype). Moreover, 100 stored sera collected during summer 2018 (N = 50) and winter season 2018/2019 (N = 50) were included to demonstrate test specificities. These varied from 96.0% (DiaSorin) to 100% (Epitope EDI). A subset of sera were retested with a lateral flow test (STANDARD Q COVID-19 IgM/IgG Duo) and a considerably lower sensitivity was noted. Overall, the diagnostic accuracy of the six SARS-CoV-2 IgG/total antibody assays was good and varied from 92.9% (Euroimmun) to 98.4% (Abbott). Due to the different specificities, results of commercially available SARS-CoV-2 antibody tests should be interpreted with caution. A high proportion of antibody-positive patient sera demonstrated neutralizing capacity against SARS-CoV-2. url: https://doi.org/10.1101/2020.06.15.20131672 doi: 10.1101/2020.06.15.20131672 id: cord-291710-ixun0c8g author: Su, Haixia title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 words: 2572.0 sentences: 154.0 pages: flesch: 53.0 cache: ./cache/cord-291710-ixun0c8g.txt txt: ./txt/cord-291710-ixun0c8g.txt summary: A crystal structure of SARS-CoV-2 3CLpro in complex with baicalein, the first non-covalent, non-peptidomimetic small-molecule inhibitor, was also determined, revealing a unique binding mode of this natural product with the protease. To validate the binding of baicalin and baicalein with SARS-CoV-2 3CLpro and exclude the suspicion of being the pan-assay interference compounds (PAINS) (15) , their binding affinities with the protease were measured by isothermal titration calorimetry (ITC), widely known as an invaluable tool used to determine thermodynamic parameters of protein-ligand interactions such as Kd (Fig. 1, A and B ; Table 1 ). Moreover, the ITC profiles in combination with their chemical structures suggest that baicalin and baicalein act as noncovalent inhibitors of SARS-CoV-2 3CLpro with a high ligand binding efficiency. The mode of action of baicalein and the structural determinants associated with its binding with SARS-CoV-2 3CLpro were further explored using X-ray protein crystallography. abstract: Human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 19 (COVID-19) and there is currently no cure. The 3C-like protease (3CLpro), a highly conserved protease indispensable for replication of coronaviruses, is a promising target for development of broad-spectrum antiviral drugs. To advance the speed of drug discovery and development, we investigated the inhibition of SARS-CoV-2 3CLpro by natural products derived from Chinese traditional medicines. Baicalin and baicalein were identified as the first non-covalent, non-peptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography is distinctly different from those of known inhibitors. Baicalein is perfectly ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to prevent the peptide substrate approaching the active site. The simple chemical structure, unique mode of action, and potent antiviral activities in vitro, coupled with the favorable safety data from clinical trials, emphasize that baicalein provides a great opportunity for the development of critically needed anti-coronaviral drugs. url: https://doi.org/10.1101/2020.04.13.038687 doi: 10.1101/2020.04.13.038687 id: cord-312305-ll29frwc author: Sun, Shihui title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 words: 4720.0 sentences: 270.0 pages: flesch: 52.0 cache: ./cache/cord-312305-ll29frwc.txt txt: ./txt/cord-312305-ll29frwc.txt summary: Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. We further characterized the in vivo replication dynamics of MASCp6 in both young and aged mice, and the results from qRT-PCR showed that high levels of SARS-CoV-2 subgenomic RNAs were persistent in the lung and tracheas till 4 day post infection (dpi) in aged mice (Fig. 1E) . The skewed age distribution of COVID-19 disease was reproduced in the MASCp36 infected mouse model where more severe symptoms were observed in aged mice when compared to young mice. In addition to the age-related skewed distribution of COVID-19, gender-related differences in distribution of COVID-19 disease is also recapitulated in this MASCp36 infected mouse model with increased susceptibility and enhanced pathogenicity observed in male mice when compared to their female counterparts. abstract: The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was ∼100 PFU in aged, male BALB/c mice. Deep sequencing identified three amino acid mutations, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, which significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of mACE2 in complex with the RBD of MASCp36 at 3.7-angstrom resolution elucidates molecular basis for the receptor-binding switch driven by amino acid substitutions. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in mice. One sentence summary A mouse adapted SARS-CoV-2 strain that harbored three amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice. url: https://doi.org/10.1101/2020.11.10.377333 doi: 10.1101/2020.11.10.377333 id: cord-352909-s11tpfoq author: Sun, Zhiping title: Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions date: 2020-08-14 words: 1747.0 sentences: 106.0 pages: flesch: 66.0 cache: ./cache/cord-352909-s11tpfoq.txt txt: ./txt/cord-352909-s11tpfoq.txt summary: Survival of SARS-COV-2 under liquid medium, dry filter paper and acidic conditions Zhiping Sun 1 , Xia Cai 1 , Chenjian Gu 2 , Rong Zhang 2 , Wendong Han 1 , Yun Qian 1 , Yuyan Wang 2 , Wei Xu 2 , Yang Wu 2 , Xunjia Cheng 2 , Zhenghong Yuan 2 , Youhua Xie 2 and Di Qu 1, 2 Dear Editor, The pneumonia caused by a novel coronavirus was first reported in December 2019 in Wuhan of China, and since then has become a pandemic 1, 2 . Here, we first investigated the infectivity of SARS-COV-2 using a plaque-purified strain nCoV-SH01 isolated from a patient in Shanghai (GenBank MT121215) 6 , studied subsequently its stability in liquid medium, on dry filter paper, and under acidic condition (pH2.2) at RT. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32821426/ doi: 10.1038/s41421-020-00191-9 id: cord-268718-tt07cwrf author: Tan, Heng Wee title: Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection date: 2020-06-30 words: 6346.0 sentences: 400.0 pages: flesch: 52.0 cache: ./cache/cord-268718-tt07cwrf.txt txt: ./txt/cord-268718-tt07cwrf.txt summary: 54 Virus infectivity study has indicated that the SARS-CoV-2 is able to utilize ACE2 of human, Chinese horseshoe bats, civet, and pig but was not able to use mouse ACE2. The roles of ACE2 expression in SARS-CoV-2 pathogenesis and human COVID-19 susceptibility are largely unknown. B, ACE2 expression in lung cancer patients with different smoking histories analyzed using similar methods as described previously 106 other symptoms in addition to respiratory symptoms, suggesting that SARS-CoV-2 could perhaps infect other organs (Figure 3 ). 118 In addition to sputum, SARS-CoV-2 RNA has been detected in the stools of a COVID-19 patient, 119 F I G U R E 3 Tissue distribution of angiotensin-converting enzyme 2 (ACE2) expression and potential COVID-19 susceptibility. Expression of elevated levels of proinflammatory cytokines in SARS-CoV-infected ACE2 + cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS abstract: Coronavirus (CoV) disease 2019 (COVID‐19) is an ongoing pandemic caused by severe acute respiratory syndrome CoV 2 (SARS‐CoV‐2). The highly contagious SARS‐CoV‐2 belongs to the genus Betacoronavirus, and it is phylogenetically closely related to SARS‐CoV, a human CoV that caused an outbreak back in 2002 to 2003. Both SARS‐CoV‐2 and SARS‐CoV enter human cells via the interactions between viral crown‐like spike protein and human angiotensin‐converting enzyme 2 (ACE2) receptor. Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross‐species transmissibility, and COVID‐19 susceptibility. We also provide our perspectives on COVID‐19 treatment and prevention. url: https://www.ncbi.nlm.nih.gov/pubmed/32602627/ doi: 10.1002/rmv.2122 id: cord-322051-89wgv100 author: Tanasa, Ingrid Andrada title: Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known? date: 2020-05-28 words: 2260.0 sentences: 132.0 pages: flesch: 44.0 cache: ./cache/cord-322051-89wgv100.txt txt: ./txt/cord-322051-89wgv100.txt summary: This study summarizes the existing data regarding the association of anosmia and ageusia with the SARS-CoV-2 infection. In a retrospective observational study, Klopfenstein et al (20) reported that 54 patients (47%) with confirmed SARS-CoV-2 infection developed anosmia, 4.4 (±1.9) days after infection onset, and that was the third symptom to manifest in 38% (22/52) of the cases. Some authors reported three mechanisms for anosmia in COVID-19 patients: i) local infection of support cells and vascular pericytes in the nose and olfactory bulb that may affect the function of bipolar neurons or mitral cells; ii) damage to support cells in the sensory epithelium that may indirectly influence the signaling pathway from sensory neurons to the brain; and iii) damage to sustentacular cells and Bowman''s gland cells that could lead to diffuse morphological damage to the olfactory sensory epithelium and altering of smell perception (28, 29) . Further research is needed to demonstrate the association between anosmia and ageusia with SARS-CoV-2 infection, the clinical manifestations determined by variants of ACE2 receptor, and recovery rates of olfactory and gustative dysfunction, and specific treatment protocols of these manifestations. abstract: In 2020 a new pandemic caused by the SARS-CoV-2 coronavirus is affecting the lives of millions of patients and healthcare workers worldwide. The clinical picture of this infection is in a dynamic process of discovery, and more symptoms emerge as the clinicians observe and diagnose manifestations that affect multiple organs. Anosmia (loss of smell), and ageusia (loss of taste) become more frequently cited as independent symptoms or in association with the most common manifestations of the disease, such as fever, cough and dyspnea. A thorough screening program will prevent most nosocomial and community-acquired infections by promoting efficient triage and specific measures such as isolation of the patients. Therefore, it is important to include frequent symptoms in the anamnesis and questionnaires to select those patients who might benefit from testing, isolation, and treatment. This study summarizes the existing data regarding the association of anosmia and ageusia with the SARS-CoV-2 infection. It also aims to describe manifestations of these, particularly in the clinical picture of all symptomatic patients. url: https://doi.org/10.3892/etm.2020.8808 doi: 10.3892/etm.2020.8808 id: cord-269275-b7xxk48t author: Tang, Xiaojia title: Neurological manifestations in COVID-19 and its possible mechanism date: 2020-09-27 words: 4631.0 sentences: 260.0 pages: flesch: 44.0 cache: ./cache/cord-269275-b7xxk48t.txt txt: ./txt/cord-269275-b7xxk48t.txt summary: SARS-CoV-2 has been reported to be associated with Guillain-Barré syndrome, rhabdomyolysis, acute cerebrovascular disease, central nervous system infections and other neurological diseases. Four formal reports have described neurological problems in SARS patients, including polyneuropathy [35] , myopathy and rhabdomyolysis [36] , large artery ischemic stroke [37] and central nervous system infections [38] . In a study by Mao et al., 214 patients diagnosed with COVID-19 were enrolled, and six (2.80%) of them developed acute cerebrovascular disease (five cases of ischemic stroke and one case of cerebral hemorrhage). Strokes are not uncommon in critically ill patients with multiple comorbidities, so SARS-CoV-2 infections in humans may increase the risk of stroke. Since some COVID-19 patients have complained of headaches, nausea etc, care providers should be alert for central nervous system infections caused by SARS-CoV-2 if such patients also exhibit symptoms such as a fever, epilepsy and disturbances of consciousness. abstract: In December 2019, the first cases of the acute respiratory illness now known as Corona Virus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The main clinical manifestations of COVID-19 are a fever, dry cough and general weakness, although in some patients, a headache, tight chest, diarrhea, etc. are the first clinical manifestations. Neurological practice is involved in all aspects of medicine, from primary care for patients with migraines to consultations with patients in the intensive care unit. Few disorders spare the nervous system, and newly emerging infections are no exception. As neurologists, we are concerned about the effects of SARS-CoV-2 infections on the nervous system. Multiple neuropathy, rhabdomyolysis, cerebrovascular disease, central nervous system infections and other common neurological diseases require attention during this outbreak. url: https://doi.org/10.18632/aging.103732 doi: 10.18632/aging.103732 id: cord-015503-j99cgsjt author: Tang, Xiaolu title: On the origin and continuing evolution of SARS-CoV-2 date: 2020-03-03 words: 5243.0 sentences: 292.0 pages: flesch: 59.0 cache: ./cache/cord-015503-j99cgsjt.txt txt: ./txt/cord-015503-j99cgsjt.txt summary: Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Further, the genomic sequences of SARS-CoV-2 viruses isolated from a number of patients share sequence identity higher than 99.9%, suggesting a very recent host shift into humans [1] [2] [3] . abstract: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107875/ doi: 10.1093/nsr/nwaa036 id: cord-274841-rcdoewwv author: Tay, Matthew Zirui title: The trinity of COVID-19: immunity, inflammation and intervention date: 2020-04-28 words: 7186.0 sentences: 383.0 pages: flesch: 43.0 cache: ./cache/cord-274841-rcdoewwv.txt txt: ./txt/cord-274841-rcdoewwv.txt summary: Monoclonal antibodies targeting the When severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells expressing the surface receptors angiotensin-converting enzyme 2 (ACE2) and TMPRSS2, the active replication and release of the virus cause the host cell to undergo pyroptosis and release damageassociated molecular patterns, including ATP, nucleic acids and ASC oligomers. While there are no clinical trials specifically testing these drugs against COVID-19 at the time of writing, when camostat mesylate was tested on SARS-CoV-2 isolated from a patient, it prevented entry of the virus into lung cells 44, 50 . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Neutralizing antibodies in patients with severe acute respiratory syndrome-associated Nature reviews | Immunology coronavirus infection abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation. url: https://www.ncbi.nlm.nih.gov/pubmed/32346093/ doi: 10.1038/s41577-020-0311-8 id: cord-350352-wgppovfx author: Temmam, Sarah title: Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus date: 2020-08-29 words: 2470.0 sentences: 125.0 pages: flesch: 54.0 cache: ./cache/cord-350352-wgppovfx.txt txt: ./txt/cord-350352-wgppovfx.txt summary: In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. We investigated the presence of SARS-CoV-2 infection of domestic cats (n = 9) and dogs (n = 12) living in close contact with a cluster of French veterinary students, their owners (n = 18), whose median age was 23 years (21-28 years). Although based on a small cluster of 21 domestic pets, our cross-sectional study based on the antibody response one month after exposure to the index case points to J o u r n a l P r e -p r o o f Journal Pre-proof undetectable interspecific transmission of the SARS-CoV-2 virus between COVID-19 patients and domestic dogs or cats under natural exposure conditions. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no antibodies against SARS-CoV-2 were detectable in their blood one month after the index case was reported, using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions. url: https://www.ncbi.nlm.nih.gov/pubmed/32904469/ doi: 10.1016/j.onehlt.2020.100164 id: cord-325324-kh2aal5n author: Teng, Shaolei title: ACE2 Enhance Viral Infection or Viral Infection Aggravate the Underlying Diseases date: 2020-08-06 words: 4403.0 sentences: 274.0 pages: flesch: 53.0 cache: ./cache/cord-325324-kh2aal5n.txt txt: ./txt/cord-325324-kh2aal5n.txt summary: SARS-CoV-2 spike protein (S) is cleaved by the human furin enzyme to generate S1, which binds to the host receptor, ACE-2. It is possible that the released free spike or the cleaved S1 protein in the blood might bind to cellular membrane ACE2 of heart, artery and alveolar lung cells to block the conversion of Angiotensin II to Ang-(1-7) and/or Angiotensin I to Ang-(1-9), which is consistent with a previous experimental result on SARS-CoV-1 (59) . Therefore, our hypothesis, as shown in the right side of Fig. 1 as "Viral aggravating existing diseases", is that comorbidities in COVID-19 patients are aggravated by the infection of SARS-CoV-2 to causes higher fatalities because the viral S protein interacts with ACE2 to inhibit ACE2 function. The claims that COVID-19 disproportionately affects the individuals of minority groups and aged people are not only supported by reported data but also by our hypothesis that SARS-CoV-2 infection generates spike protein that interacts with ACE2 to either exhaust ACE2 or inhibit ACE2 function or both so that the comorbidities are aggravated (Figure 1 ). abstract: ACE2 plays a critical role in SARS-CoV-2 infection to cause COVID-19 and SARS-CoV-2 spike protein binds to ACE2 and probably functionally inhibits ACE2 to aggravate the underlying diseases of COVID-19. The important factors that affect the severity and fatality of COVID-19 include patients' underlying diseases and ages. Therefore, particular care to the patients with underlying diseases is needed during the treatment of COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32832038/ doi: 10.1016/j.csbj.2020.08.002 id: cord-345929-z7yfegr5 author: Thakur, Suman S. title: Proteomics and Its Application in Pandemic Diseases date: 2020-11-06 words: 1355.0 sentences: 94.0 pages: flesch: 39.0 cache: ./cache/cord-345929-z7yfegr5.txt txt: ./txt/cord-345929-z7yfegr5.txt summary: found that the antimalarial drug metaquine and anti-HIV antiretroviral saquinavir interact with four SARS-CoV-2 receptors, including Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S protein), interacting with human ACE2; therefore, they may be repurposed for COVID-19 treatment. Furthermore, Maffucci and Contini used an in silico approach to find drug candidates against the main proteinase and spike protein of SARS-CoV-2. suggested that the antigenic peptides generated from the S1 spike glycoprotein of SARS-CoV-2 using aminopeptidases ERAP1, ERAP2, and IRAP might be helpful in selecting better epitopes for immunogenic studies and the design of a vaccine for COVID-19. Interestingly, a computational method was used to find an allosteric site on the SARS-CoV-2 spike protein by Di Paola et al., as its detection would weaken the spike−ACE2 interaction and thereby reduce the viral infection. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33153265/ doi: 10.1021/acs.jproteome.0c00824 id: cord-321166-nvphu1fm author: Thomson, Emma C. title: The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date: 2020-11-05 words: 9813.0 sentences: 514.0 pages: flesch: 55.0 cache: ./cache/cord-321166-nvphu1fm.txt txt: ./txt/cord-321166-nvphu1fm.txt summary: We find that the N439K mutation is associated with a similar clinical spectrum of disease and slightly higher viral loads in vivo compared with isolates with the wild-type N439 residue, and that it results in immune escape from polyclonal sera from a proportion of recovered individuals and a panel of neutralizing mAbs. N439K provides a sentinel example of immune escape, indicating that RBM variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of mAbs. Long term control of the pandemic will require systematic monitoring of immune escape variants and selection of strategies that address the variants circulating in targeted populations. Fitness of this variant, N439K, was demonstrated by repeated emergence by convergent evolution, spread to multiple countries and significant representation in the SARS-CoV-2 sequence databases, the fact that the N439K RBD retains a high affinity interaction with the hACE2 receptor, efficient viral replication in cultured cells, and no disease attenuation in a large cohort of infected individuals. abstract: SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics. url: https://doi.org/10.1101/2020.11.04.355842 doi: 10.1101/2020.11.04.355842 id: cord-297842-hkr1wm3k author: Tilley, Kimberly title: A Cross-Sectional Study Examining the Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in a University Student Population date: 2020-10-15 words: 3894.0 sentences: 197.0 pages: flesch: 43.0 cache: ./cache/cord-297842-hkr1wm3k.txt txt: ./txt/cord-297842-hkr1wm3k.txt summary: PURPOSE: The aim of the study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university student population. METHODS: This was a cross-sectional survey study based on the World Health Organization population-based seroepidemiological investigational protocol for SARS-CoV-2 conducted between April 29, 2020, and May 8, 2020, examining SARS-CoV-2 antibody prevalence among 790 university students in Los Angeles, CA. With the goal of having the sample distributions match distributions in the population, these strata were selected based on internal university data, indicating that females are more likely to participate in health-related research projects compared with males, and fewer undergraduates (36.4%) spent the end of the Spring 2020 semester in Los Angeles relative to graduate students (76.5%). Seroprevalence of SARS-CoV-2 antibodies in a Los Angeles university student population as of May 8, 2020, was estimated to be 4.0%. abstract: PURPOSE: The aim of the study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university student population. METHODS: This was a cross-sectional survey study based on the World Health Organization population-based seroepidemiological investigational protocol for SARS-CoV-2 conducted between April 29, 2020, and May 8, 2020, examining SARS-CoV-2 antibody prevalence among 790 university students in Los Angeles, CA. Participants completed a questionnaire on potential risk factors before blood sampling. Samples were analyzed using the EUROIMMUN Anti-SARS-CoV-2 ELISA (IgG) for the qualitative detection of IgG class antibodies to SARS-CoV-2 in human serum or plasma. RESULTS: The estimated prevalence of SARS-CoV-2 antibody was 4.0% (3.0%, 5.1%). Factors associated with having a positive test included history of anosmia and/or loss of taste (95% CI: 1.4–9.6). A history of respiratory symptoms, with or without fever, was not associated with a positive antibody test. CONCLUSIONS: Prevalence of SARS-CoV-2 antibodies in the undergraduate and graduate student university population was similar to community prevalence. url: https://www.sciencedirect.com/science/article/pii/S1054139X2030522X doi: 10.1016/j.jadohealth.2020.09.001 id: cord-337430-c2vdnml7 author: Timpka, Toomas title: Sports Health During the SARS-Cov-2 Pandemic date: 2020-05-02 words: 2261.0 sentences: 122.0 pages: flesch: 47.0 cache: ./cache/cord-337430-c2vdnml7.txt txt: ./txt/cord-337430-c2vdnml7.txt summary: In December 2019, the Chinese city of Wuhan reported an outbreak of SARS-Cov-2 (severe acute respiratory syndrome coronavirus-2) infection that causes the Covid-19 disease, an atypical pneumonia [1] . The national public health agencies choose social distancing regulations based on an overall assessment of how critical certain activities are for society as a whole and whether motivation to comply with the rules can be assumed. During the SARS-Cov-2 pandemic, effectively all population-level interventions include the recommendation that social contacts with the elderly, and especially the senior elderly, are to be reduced to an absolute minimum. Sports organisations should develop a pandemic response strategy that addresses the needs of its athletes and coaches, while complying with the regulations and recommendations issued by the government and national public health agency. The temporary frameworks for organised sports practice and competitions must be developed based on the social distancing and quarantine protocols activated during the pandemic. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32361898/ doi: 10.1007/s40279-020-01288-7 id: cord-325614-e9hnhzfg author: Todorov, German title: A Possible Path towards Rapid Development of Live-Attenuated SARS-CoV-2 Vaccines: Plunging into the Natural Pool date: 2020-10-14 words: 3122.0 sentences: 145.0 pages: flesch: 41.0 cache: ./cache/cord-325614-e9hnhzfg.txt txt: ./txt/cord-325614-e9hnhzfg.txt summary: Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness. The proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, potentially leading to a more rapid cycle of vaccine development, as well as higher vaccine effectiveness. If the candidate attenuated SARS-CoV-2 strain is easily transmissible, we would need to evaluate whether a live-attenuated virus that causes a very mild form of infection but is easy to transmit can be considered sufficiently safe for use as a vaccine, or whether it needs to be further attenuated in the lab, which could slow down the development of the vaccine. All in all, at present there are too many unknowns to predict how much screening of suitable individuals in high-risk subpopulations will be required to find naturally-evolved candidate strains for the development of live-attenuated vaccines. abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic spreading around the world, causing massive distress to the world’s economy and affecting healthcare systems worldwide. Although some exposed individuals have no symptoms and most symptomatic infections are not severe, COVID-19 cases span a wide spectrum, ranging from mild to critical and sometimes resulting in life-threatening complications, such as pneumonia, severe respiratory distress and cardiac problems. Currently, there is no curative drug for COVID-19 and vaccines are still under development. We are presenting here a strategy for the fast development of natural live-attenuated SARS-CoV-2 vaccines. Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness. url: https://www.ncbi.nlm.nih.gov/pubmed/33066343/ doi: 10.3390/biom10101438 id: cord-252049-rgdynmla author: Tomar, Sakshi title: Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CL(pro)): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS date: 2015-06-08 words: 11805.0 sentences: 601.0 pages: flesch: 56.0 cache: ./cache/cord-252049-rgdynmla.txt txt: ./txt/cord-252049-rgdynmla.txt summary: All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Therefore, we determined the dependence of the enzymatic activity of MERS-CoV 3CL pro on the total enzyme concentration and compared it with other 3CL pro enzymes from HKU4, HKU5, and SARS coronaviruses (Fig. 2) . The kinetic data for all four 3CL pro enzymes, MERS-CoV, HKU4-CoV, HKU5-CoV, and SARS-CoV, fit well to this model, and the resulting values for the monomer-dimer equilibrium dissociation constant, K d , and apparent turnover number, k cat , for each enzyme are provided in Table 2 . Compound 11 also forms two direct and one water-mediated hydrogen bond interactions with amino acids in the MERS-CoV 3CL pro active site (Fig. 6E) . abstract: All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (K(d) ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents. url: https://www.ncbi.nlm.nih.gov/pubmed/26055715/ doi: 10.1074/jbc.m115.651463 id: cord-289535-srrfr1es author: Tregoning, J. S. title: Vaccines for COVID‐19 date: 2020-10-18 words: 14329.0 sentences: 793.0 pages: flesch: 44.0 cache: ./cache/cord-289535-srrfr1es.txt txt: ./txt/cord-289535-srrfr1es.txt summary: One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial abstract: Since the emergence of COVID‐19, caused by the SARS‐CoV‐2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID‐19 pandemic, production needs to be scaled‐up from a small number of preclinical doses to enough filled vials to immunize the world’s population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS‐CoV‐2 and the potential for vaccine‐induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases. url: https://www.ncbi.nlm.nih.gov/pubmed/32935331/ doi: 10.1111/cei.13517 id: cord-289716-nleql08z author: Tsitsilonis, Ourania E. title: Seroprevalence of Antibodies against SARS-CoV-2 among the Personnel and Students of the National and Kapodistrian University of Athens, Greece: A Preliminary Report date: 2020-09-21 words: 3225.0 sentences: 143.0 pages: flesch: 44.0 cache: ./cache/cord-289716-nleql08z.txt txt: ./txt/cord-289716-nleql08z.txt summary: Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. According to the manufacturer''s package insert, Elecsys ® Anti-SARS-CoV-2 exhibits high overall clinical specificity of 99.81% with no cross-reactivity to the common cold coronaviruses; clinical sensitivity, determined by testing a total of 204 samples from 69 symptomatic patients with a PCR-confirmed SARS-CoV-2 infection, is 100% for samples collected ≥14 days after PCR confirmation in this collective; these values were verified in our study by measuring 25 RT-qPCR SARS-CoV-2 positive and 25 negative samples. abstract: Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. The National and Kapodistrian University of Athens (ΝΚUA), especially its health-care/medical personnel, has been actively involved in the first line of state responses to COVID-19. To estimate the prevalence of antibodies (Igs) against SARS-CoV-2 among NKUA members, we designed a five consecutive monthly serosurvey among randomly selected NKUA consenting volunteers. Here, we present the results from the first 2500 plasma samples collected during June–July 2020. Twenty-five donors were tested positive for anti-SARS-CoV-2 Igs; thus, the overall seroprevalence was 1.00%. The weighted overall seroprevalence was 0.93% (95% CI: 0.27, 2.09) and varied between males [1.05% (95% CI: 0.18, 2.92)] and females [0.84% (95% CI: 0.13, 2.49)], age-groups and different categories (higher in participants from the School of Health Sciences and in scientific affiliates/faculty members/laboratory assistants), but no statistical differences were detected. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. Given that approximately one in three infections was asymptomatic, continuous monitoring of the progression of the pandemic by assessing Ig seroprevalence is needed. url: https://doi.org/10.3390/life10090214 doi: 10.3390/life10090214 id: cord-280068-rszu1c48 author: Twomey, Julianne D. title: COVID-19 update: The race to therapeutic development date: 2020-10-24 words: 6195.0 sentences: 331.0 pages: flesch: 42.0 cache: ./cache/cord-280068-rszu1c48.txt txt: ./txt/cord-280068-rszu1c48.txt summary: We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-COV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-COV-2, such as REGN-COV2 (an antibody cocktail) and LY-COV555, as well as recombinant human soluble ACE2 protein to counteract SARS-COV-2 binding to the transmembrane ACE2 receptor in target cells. The current review highlights the potential therapeutic strategies for the treatment of COVID-19, including small molecule drugs and therapeutic proteins to target the SARS-CoV-2 viral entry, viral amplification or the host immune responses. abstract: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents an unprecedented challenge to global public health. At the time of this review, COVID-19 has been diagnosed in over 40 million cases and associated with 1.1 million deaths worldwide. Current management strategies for COVID-19 are largely supportive, and while there are more than 2000 interventional clinical trials registered with the U.S. National Library of Medicine (clinicaltrials.gov), results that can clarify benefits and risks of candidate therapies are only gradually becoming available. We herein describe recent advances in understanding SARS-COV-2 pathobiology and potential therapeutic targets that are involved in viral entry into host cells, viral spread in the body, and the subsequent COVID-19 progression. We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-COV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-COV-2, such as REGN-COV2 (an antibody cocktail) and LY-COV555, as well as recombinant human soluble ACE2 protein to counteract SARS-COV-2 binding to the transmembrane ACE2 receptor in target cells. Finally, we discuss potential drug resistance mechanisms and provide thoughts regarding clinical trial design to address the diversity in COVID-19 clinical manifestation. Of note, preventive vaccines, cell and gene therapies are not within the scope of the current review. url: https://doi.org/10.1016/j.drup.2020.100733 doi: 10.1016/j.drup.2020.100733 id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 words: 8193.0 sentences: 522.0 pages: flesch: 46.0 cache: ./cache/cord-338436-0z828org.txt txt: ./txt/cord-338436-0z828org.txt summary: Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. abstract: Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development. url: https://www.ncbi.nlm.nih.gov/pubmed/32916958/ doi: 10.3390/v12091006 id: cord-349643-jtx7ni9b author: Uyeki, Timothy M. title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus date: 2016-07-17 words: 4805.0 sentences: 200.0 pages: flesch: 31.0 cache: ./cache/cord-349643-jtx7ni9b.txt txt: ./txt/cord-349643-jtx7ni9b.txt summary: Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection abstract: Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures. url: https://doi.org/10.3201/eid2207.160022 doi: 10.3201/eid2207.160022 id: cord-274802-7ioiwsd8 author: Varghese, Praveen Mathews title: Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies date: 2020-08-19 words: 19657.0 sentences: 1033.0 pages: flesch: 42.0 cache: ./cache/cord-274802-7ioiwsd8.txt txt: ./txt/cord-274802-7ioiwsd8.txt summary: Proteomic and transcriptomic studies on bronchoalveolar lavage (BAL) samples from COVID-19 patients have also revealed considerable insights into the expression of SARS-CoV-2 receptors, co-receptors, immune responses, as well as risk factors for severe disease e.g. age and co-morbidities. Furthermore, treatment with a recombinant C5a antibody on 2 male COVID-19 patients aged 54 and 67 years showed significant benefit in suppressing complement hyperactivation, which contributes to the excessive immune response causing aggravated inflammatory lung injury, a hallmark of SARS-CoV-2 pathogenesis and lethality (242) . Consistent with endothelial injury, the significantly elevated levels of von Willebrand factor found in the patient with severe COVID-19 has led to the idea that the infection of the ACE2 expressing endothelium by SARS-CoV-2 induces injury and activates the complement , which sets up a feedback loop that maintains a state of inflammation (243, (268) (269) (270) . Initial clinical studies in China involving 100 SARS-CoV-2 infected patients, who were treated with Chloroquine, showed amelioration of pneumonia, shortened disease progression, increased resolution of lung lesions on CT, and a better virus-negative conversion (313, 314) . abstract: Abstract The current coronavirus pandemic, COVID-19, is the third outbreak of disease caused by the coronavirus family, after Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. It is an acute infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 Virus (SARS-CoV-2). The severe disease is characterised by acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Currently, no drugs or vaccine exist against the disease and the only course of treatment is symptom management involving mechanical ventilation, immune suppressants, and repurposed drugs. As such the severe form of the disease has a relatively high mortality rate. Last 6 months have seen an explosion of information related to the host receptors, virus transmission, virus structure-function relationships, pathophysiology, co-morbidities, immune response, treatment and most promising vaccines. This review takes a critically comprehensive look at various aspects of host-pathogen interaction in COVID-19. We examine genomic aspects of SARS-CoV-2, modulation of innate and adaptive immunity, complement-triggered microangiopathy, and host transmission modalities. We also examine its pathophysiological impact during pregnancy, in addition to various gaps in our knowledge. The lessons learnt from various clinical trials involving repurposed drugs have been summarised. We also highlight the rationale and likely success of the most promising vaccine candidates. url: https://www.ncbi.nlm.nih.gov/pubmed/33130519/ doi: 10.1016/j.imbio.2020.152008 id: cord-265322-3854ddb9 author: Vavougios, George D. title: A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi date: 2020-04-23 words: 1252.0 sentences: 72.0 pages: flesch: 41.0 cache: ./cache/cord-265322-3854ddb9.txt txt: ./txt/cord-265322-3854ddb9.txt summary: Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host''s metabolism as part of its lifecycle. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Their study provided the foundation for a hypothesis put forth by Fang and colleagues indicating that diabetic and hypertensive patients exposed to ACE2 inhibitors may be at an increased risk of more severe COVID-19 (7) . In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (10) . Future studies should determine SARS-CoV-2 interaction and effect on the human transcriptome, further identifying drug targets using pharmacogenomic enrichment analyses. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? abstract: COVID-19, the disease caused by the novel SARS-CoV-2, a betacoronavirus structurally similar to SARS-CoV. Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host’s metabolism as part of its lifecycle. This hypothesis is evaluated by (a) exploratory analysis of SARS-CoV / human transcriptomic interaction data and gene set enrichment analysis (b) a confirmatory, focused review of the literature based on the findings by (a). A STRING Viruses (available search for human – SARS-CoV (NCBI taxonomy Id: 9606 vs. NCBI taxonomy Id: 694009) genomic interactions reveals ten human proteins, interacting with SARS-CoV: SGTA, FGL2, SPECC1, STAT3, PHB, BCL2L1, PPP1CA, CAV1, JUN, XPO1. Gene set enrichment analyses (GSEA) with STRING on this network revealed their role as a putative protein – protein interaction network (PPI; Enrichment p-value=0.0296) mediating, viral parasitism, interleukin as well as insulin signaling, diabetes and triglyceride catabolism. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Conversely, currently there are only non-causative, observational evidence of worse outcomes for COVID-19 patients with comorbid diabetes or hyperglycemia. No study has reported on the lipid profiles of COVID-19 patients; however, lipid-targeting molecules have been proposed as agents against SARS-CoV-2. Future studies, reporting on lipid and glucose metabolism of COVID-19 patients could help elucidate the disease’s seculae and aid drug design. url: https://www.sciencedirect.com/science/article/pii/S0306987720305600?v=s5 doi: 10.1016/j.mehy.2020.109759 id: cord-309876-l0xginsa author: Vena, Antonio title: Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors date: 2020-08-27 words: 3065.0 sentences: 168.0 pages: flesch: 45.0 cache: ./cache/cord-309876-l0xginsa.txt txt: ./txt/cord-309876-l0xginsa.txt summary: A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59–3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19–6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75–6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94–88.71, p = 0.001). In the present observational study performed on a large sample of subject in northern Italy, we found the following: (1) the overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0%; (2) occupational exposure to the virus, long-term care facility residency, as well as previous symptoms of influenza-like illness or loss of sense of smell or taste were independently associated with anti-SARS-CoV-2 positivity. abstract: We aimed to assess the prevalence of and factors associated with anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in a large population of adult volunteers from five administrative departments of the Liguria and Lombardia regions. A total of 3609 individuals were included in this analysis. Participants were tested for anti-SARS-CoV-2 antibodies [Immunoglobulin G (IgG) and M (IgM) class antibodies] at three private laboratories (Istituto Diganostico Varelli, Medical Center, and Casa della Salute di Genova). Demographic data, occupational or private exposure to SARS-CoV-2-infected patients, and prior medical history consistent with SARS-CoV-2 infection were collected according to a preplanned analysis. The overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0% [398/3609; confidence interval (CI) 10.0%–12.1%]. Seroprevalence was higher in female inmates than in male inmates (12.5% vs. 9.2%, respectively, p = 0.002), with the highest rate observed among adults aged >55 years (13.2%). A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59–3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19–6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75–6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94–88.71, p = 0.001). In conclusion, we found a high prevalence (11.0%) of SARS-CoV-2 infection that is significantly associated with residing in long-term care facilities or occupational exposure to the virus. These findings warrant further investigation into SARS-CoV-2 antibody prevalence among the Italian population. url: https://www.ncbi.nlm.nih.gov/pubmed/32867328/ doi: 10.3390/jcm9092780 id: cord-280821-kc0ut4oy author: Venturini, Elisabetta title: Treatment of children with COVID-19: position paper of the Italian Society of Pediatric Infectious Disease date: 2020-09-24 words: 5481.0 sentences: 315.0 pages: flesch: 45.0 cache: ./cache/cord-280821-kc0ut4oy.txt txt: ./txt/cord-280821-kc0ut4oy.txt summary: The Italian Society of Pediatric Infectious Diseases steering and scientific committee developed a position paper on treatment of children with COVID-19, reviewing the current literature on this topic and providing indications based on the available literature data. Currently, American guidelines on COVID-19 treatment published in May 2020, recommend both in children and adults to use lopinavir/ritonavir only in the context of clinical trials, given the lack of effectiveness reported now in literature [9, 12] . The latest Chinese guidelines on SARS-Cov-2 pneumoniae do not recommend the use of a specific antiviral for the treatment of COVID-19, and nevertheless include lopinavir/ritonavir among the available therapeutic options for hospitalized patients [29] . In May 2020, following an assessment of the emergency use authorization criteria and available scientific evidence, the FDA issued an emergency use authorization allowing for the administration of remdesivir intravenously by health care providers for the treatment of COVID-19 suspected or laboratoryconfirmed in adults and pediatric patients hospitalized with severe disease [34] . abstract: A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics. url: https://doi.org/10.1186/s13052-020-00900-w doi: 10.1186/s13052-020-00900-w id: cord-316702-dj2fo8sn author: Vignesh, Ramachandran title: Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date: 2020-09-30 words: 3250.0 sentences: 169.0 pages: flesch: 45.0 cache: ./cache/cord-316702-dj2fo8sn.txt txt: ./txt/cord-316702-dj2fo8sn.txt summary: Since many studies from different geographical locations are documenting preexisting immunity to SARS-CoV-2, it will be important to define specificities of these T and B cell immune response carefully to assess their association with COVID-19 disease severity. This preexisting cross-reactive T and B cell immunity to SARS-CoV-2 may have wide implications as this could explain differential clinical outcomes in COVID-19 patients, disease severity, vaccine development, and important in accessing herd immunity for SARS-CoV-2 viral infection/COVID-19 disease. Several studies have provided strong evidence for the importance of SARS-CoV-2 specific CTLs, and T helper cells in mild and moderate patients compared to severe COVID-19 disease (27, 28, (31) (32) (33) . Several studies have provided strong evidence for the importance of SARS-CoV-2specific neutralizing antibodies in association with less disease severity in COVID-19 patients (38, 39) . A recent modelling study has estimated that about one in five individuals worldwide would be at increased risk of severe COVID-19, upon infection with SARS-CoV-2, owing to the underlying conditions. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33101320/ doi: 10.3389/fimmu.2020.586781 id: cord-281281-knelqmzx author: Villas-Boas, Gustavo R. title: The New Coronavirus (SARS-CoV-2): A Comprehensive Review on Immunity and the Application of Bioinformatics and Molecular Modeling to the Discovery of Potential Anti-SARS-CoV-2 Agents date: 2020-09-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: On March 11, 2020, the World Health Organization (WHO) officially declared the outbreak caused by the new coronavirus (SARS-CoV-2) a pandemic. The rapid spread of the disease surprised the scientific and medical community. Based on the latest reports, news, and scientific articles published, there is no doubt that the coronavirus has overloaded health systems globally. Practical actions against the recent emergence and rapid expansion of the SARS-CoV-2 require the development and use of tools for discovering new molecular anti-SARS-CoV-2 targets. Thus, this review presents bioinformatics and molecular modeling strategies that aim to assist in the discovery of potential anti-SARS-CoV-2 agents. Besides, we reviewed the relationship between SARS-CoV-2 and innate immunity, since understanding the structures involved in this infection can contribute to the development of new therapeutic targets. Bioinformatics is a technology that assists researchers in coping with diseases by investigating genetic sequencing and seeking structural models of potential molecular targets present in SARS-CoV2. The details provided in this review provide future points of consideration in the field of virology and medical sciences that will contribute to clarifying potential therapeutic targets for anti-SARS-CoV-2 and for understanding the molecular mechanisms responsible for the pathogenesis and virulence of SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32906733/ doi: 10.3390/molecules25184086 id: cord-296426-upwsdgso author: Virmani, Sarthak title: Identifying a Kidney Transplant Recipient COVID Phenotype to Aid Test Utilization in the Setting of Limited Testing Availability - Does One Exist? date: 2020-06-20 words: 4402.0 sentences: 222.0 pages: flesch: 49.0 cache: ./cache/cord-296426-upwsdgso.txt txt: ./txt/cord-296426-upwsdgso.txt summary: While it is true that other non-novel viruses tend to cause more severe disease in immunocompromised patients [1] , no conclusive data is available to suggest an increased susceptibility or severity of SARS-Cov-2 infection in immunosuppressed kidney transplant recipients (KTRs). This was a single center, retrospective chart review performed as a QAPI project to assess similarities in kidney transplant recipients who tested positive for SARS-CoV-2 as compared to those who tested negative, and guide testing recommendations in the setting of limited testing availability during the COVID-19 pandemic. We did not observe any significant association between patient gender, level of education, or history of diabetes on the SARS-CoV-2 test result. Our cohort of KTRs showed no significant difference in ALC between patients who tested positive and negative for SARS-CoV-2 (Table 3 ). Though statistically significant in our small patient cohort, larger studies of KTRs with COVID-19 disease and a history of BKV will be required to confirm and better understand this association. abstract: Abstract: The high morbidity and mortality of COVID-19 in immunocompetent patients raises significant concern for immunosuppressed kidney transplant recipients (KTRs). This level of concern, both on the part of the KTRs and transplant professionals, is heightened by a lack of prior knowledge on how SARS-CoV-2 may manifest differently in immunosuppressed patients. Characterizing how KTRs may present differently than the general population would allow for more targeted and timely evaluation and treatment of KTRs with COVID-19 infection. Methods Without prior knowledge of how this virus would affect our transplant center’s delivery of care to KTRs who are SARS-CoV-2 positive or Patients Under Investigation (PUIs), and in the setting of limited testing availability, we initiated a Quality Assurance and Improvement Project (QAPI) to track KTRs followed at our transplant center through the SARS-CoV-2 testing process. Results Of the 53 symptomatic patients, 20 (38%) tested positive for SARS-CoV-2 either on presentation to the emergency department, or referral to a designated outpatient testing center. In addition, 16 (80%) of the 20 patients who tested positive required inpatient treatment. Intriguingly, patients with a history of polyoma BK viremia (BKV) had a higher incidence of testing positive for SARS-CoV-2 compared to patients without history of BKV (80% and 28%, respectively; p= 0.002). The Positive Predictive Value and Likelihood ratio was 80% and 6.6 for this association, respectively. Among our KTRs tested, those receiving belatacept had a lower likelihood of testing positive for SARS-CoV-2. This finding approached, but did not achieve, statistical significance (p=0.06). url: https://doi.org/10.1016/j.transproceed.2020.05.033 doi: 10.1016/j.transproceed.2020.05.033 id: cord-253665-1dn3ek34 author: Vishnubalaji, Radhakrishnan title: Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response date: 2020-07-07 words: 5427.0 sentences: 301.0 pages: flesch: 42.0 cache: ./cache/cord-253665-1dn3ek34.txt txt: ./txt/cord-253665-1dn3ek34.txt summary: Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) on Phenomenal changes in ncRNA expression are also seen within host cells, which can play a major role in respiratory virus pathogenesis, with long non-coding RNAs (lncRNAs) exhibiting higher tissue specificity than coding genes [30] . Disease and function analysis on the differentially expressed genes revealed the most significant enrichment in pathways related to reactive oxygen species, induction of apoptosis and necrosis, as well as activation of neutrophils in SARS-CoV-2 infected NHBE cells (Figure 3a,b) . The top ten activated upstream regulator networks (CST5, IFNG, IFNL1, IFNA2, SPI1, RNY3, PRL, TGM2 , miR-122 and miR-122-5p) in lung tissue derived from COVID-19 patient based on transcriptome and IPA analyses, revealed the enrichment of functions related to immune system associated JAK-STAT cascade, type 1 interferon receptor binding, cytokine receptor binding, and MHC 1 biosynthesis (Figure 6a and Supplementary Table S10 ). abstract: The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated. url: https://doi.org/10.3390/genes11070760 doi: 10.3390/genes11070760 id: cord-332778-rf47ptj6 author: Vivarelli, Silvia title: Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial? date: 2020-08-10 words: 7447.0 sentences: 374.0 pages: flesch: 44.0 cache: ./cache/cord-332778-rf47ptj6.txt txt: ./txt/cord-332778-rf47ptj6.txt summary: It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. Given their immune-compromised status, cancer patients infected by SARS-CoV-2 might be at a higher risk of developing severe and critical consequences upon COVID-19, including ARDS, septic shock and acute myocardial infarction [29] [30] [31] . Nevertheless, cancer patients, when infected by SARS-CoV-2 might develop more severe outcomes, if anti-cancer treatments induce a weakening of the host immune health [38] . Since the beginning of this pandemic, nine independent clinical studies have been published about the risks possibly related to SARS-CoV-2 infection in patients with cancer. In line with this concept, three additional independent clinical studies are currently enrolling non-cancer COVID-19 patients to test the efficacy of administering ICIs to reshape the impaired immune system of SARS-CoV-2 infected individuals (i.e., NCT04268537; NCT04356508 and NCT04413838). abstract: The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action. url: https://doi.org/10.3390/cancers12082237 doi: 10.3390/cancers12082237 id: cord-304306-rxjahqwh author: Vlachakis, Dimitrios title: Molecular mechanisms of the novel coronavirus SARS-CoV-2 and potential anti-COVID19 pharmacological targets since the outbreak of the pandemic date: 2020-10-08 words: 8517.0 sentences: 459.0 pages: flesch: 48.0 cache: ./cache/cord-304306-rxjahqwh.txt txt: ./txt/cord-304306-rxjahqwh.txt summary: The currently available antiviral option for hospitalized patients is remdesivir, which may inhibit the replication process by targeting the RdRp. Previously proposed treatments for hospitalized patients included hydroxychloroquine, which thought to disrupt virus endocytosis, and lopinavir/ritonavir, which thought to inhibit SARs-CoV-2 main protease (Astuti and Ysrafil, 2020; Magro, 2020) . Silibilin is predicted to have a dual activity against SARS-CoV-2 infection; silibilin can potentially reduce viral replication activity by targeting NSP12 as a remdesivir-like inhibitor, and modulate inflammatory responses by direct inhibition of STAT3 (BoschBarrera et al., 2020) . A recombinant form of the human ACE2 protein was synthesized as a therapeutic treatment for COVID-19, functioning as a decoy for SARS-CoV-2 and essentially preventing the virus from binding to the cell surface ACE2 (Schuster et al., 2010) . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response abstract: The novel coronavirus SARS-CoV-2 has emerged as a severe threat against public health and global economies. COVID-19, the disease caused by this virus, is highly contagious and has led to an ongoing pandemic. SARS-CoV-2 affects, mainly, the respiratory system, with most severe cases primarily showcasing acute respiratory distress syndrome. Currently, no targeted therapy exists, and since the number of infections and death toll keeps rising, it has become a necessity to study possible therapeutic targets. Antiviral drugs can target various stages of the viral infection, and in the case of SARS-CoV-2, both structural and non-structural proteins have been proposed as potential drug targets. This review focuses on the most researched SARS-CoV-2 proteins, their structure, function, and possible therapeutic approaches. url: https://doi.org/10.1016/j.fct.2020.111805 doi: 10.1016/j.fct.2020.111805 id: cord-348301-bk80pps9 author: Wahl, Angela title: Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 date: 2020-09-24 words: 4279.0 sentences: 238.0 pages: flesch: 47.0 cache: ./cache/cord-348301-bk80pps9.txt txt: ./txt/cord-348301-bk80pps9.txt summary: Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Human lung tissues of LoM were inoculated with SARS-CoV-2 and titers of replication competent virus determined 2, 6, and 14 days post-exposure (Fig. 1c , Extended Data Table 2 ). Collectively, our results indicate that LoM re ect the pathogenic effects in icted by SARS-CoV-2 on the human lung and demonstrate their utility as a single in vivo platform to evaluate and compare the replication and pathogenesis of past, present, and future pre-emergent, epidemic, and pandemic coronaviruses accelerating the development and testing of pre-exposure prophylaxis agents such as EIDD-2801. abstract: All known recently emerged human coronaviruses likely originated in bats. Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbor endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained Type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a pre-exposure prophylaxis strategy for coronavirus infection. Our results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32995766/ doi: 10.21203/rs.3.rs-80404/v1 id: cord-262328-q7mt0xve author: Wajnberg, Ania title: Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study date: 2020-09-25 words: 4419.0 sentences: 216.0 pages: flesch: 54.0 cache: ./cache/cord-262328-q7mt0xve.txt txt: ./txt/cord-262328-q7mt0xve.txt summary: In this observational study, we ran an outreach programme in the New York City (NY, USA) area, including parts of Connecticut and New Jersey, to identify people who had recovered from SARS-CoV-2 infection for nasopharyngeal PCR (cobas 6800; Roche Diagnostics, Indianapolis, IN, USA) and serum IgG titre measurement (ELISA; Icahn School of Medicine at Mount Sinai, New York, NY, USA). We did not find reports of ELISA antibody assays as large as this one from areas with major COVID-19 hotspots, and found mixed and growing reports of IgG response to and PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over time. In the 584 participants for whom both nasopharyngeal PCR testing and serum antibody testing was available, SARS-CoV-2 RNA was detected in 249 (43%) at a median of 20 days (IQR 18-23) from symptom onset and 12 days (9-14) from symptom resolution. abstract: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. METHODS: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. FINDINGS: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. INTERPRETATION: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. FUNDING: None. url: https://www.ncbi.nlm.nih.gov/pubmed/33015652/ doi: 10.1016/s2666-5247(20)30120-8 id: cord-351115-dy81dtnk author: Wang, Chen title: Identification of evolutionarily stable sites across the SARS-CoV-2 proteome date: 2020-10-20 words: 6133.0 sentences: 310.0 pages: flesch: 50.0 cache: ./cache/cord-351115-dy81dtnk.txt txt: ./txt/cord-351115-dy81dtnk.txt summary: This study addresses both by utilizing evolutionary information from SARS-CoV-2 sequence and structural data to search for actionable functional sites for each protein in the SARS-CoV-2 genome. Here we systematically suggest potential drug target sites for most SARS-CoV-2 proteins based on evolutionary information. This relative ranking re ects the variation entropy of each sequence position within and across the branches of an associated phylogenetic tree, revealing evolutionary pressure points that correspond to functional and structural determinants, and the protein sites at which they often cluster (30) . As in our approach to discover ET drug sites, we combined ET residue ranking information with sequencing data from SARS-CoV-2 isolates to arrive at linear peptides along the proteome that are evolutionarily important and also show little variation in the current outbreak ( Figure S6 , Dataset S5). The data include, for example, multiple sequence alignments, precalculated ET ranks, and predicted epitopes (both linear and structural) for all SARS-CoV-2 proteins. abstract: Since the first recognized case of COVID-19, more than 30 million people have been infected worldwide. Despite global efforts in drug and vaccine development to fight the disease, there is currently no vaccine or drug cure for COVID-19, though some drugs reduce severity and hasten recovery. Here we interrogate the evolutionary history of the entire SARS-CoV-2 proteome to identify functional sites that can inform the search for treatments. Combining this information with the mutations observed in the current COVID-19 outbreak, we systematically and comprehensively define evolutionarily stable sites that are useful drug targets. Several experimentally-validated effective drugs interact with these proposed target sites. In addition, the same evolutionary information can prioritize cross reactive antigens that are useful in directing multi-epitope vaccine strategies to illicit broadly neutralizing immune responses to the betacoronavirus family. Although the results are focused on SARS-CoV-2, these approaches are based upon evolutionary principles and are agnostic to organism or infective agent. url: https://doi.org/10.21203/rs.3.rs-95030/v1 doi: 10.21203/rs.3.rs-95030/v1 id: cord-294212-nlekz39f author: Wang, Dongliang title: Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design date: 2020-07-03 words: 6072.0 sentences: 305.0 pages: flesch: 54.0 cache: ./cache/cord-294212-nlekz39f.txt txt: ./txt/cord-294212-nlekz39f.txt summary: Linear B-cell epitopes of the SARS-CoV-2 S protein were predicted by BepiPred 2.0 in IEDB (BepiPred 2.0., Immune Epitope Database and Analysis Resource, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA) with a threshold of 0.55 (corresponding specificity > 0.817 and sensitivity < 0.292), and only the epitopes with more than 8 residues were considered for subsequent antigenicity analysis. Discontinuous B-cell epitopes were predicted via the DiscoTope 2.0 server tool in IEDB with a default threshold of −3.7 (corresponding specificity > 0.75 and sensitivity < 0.47), based on the 3-dimensional (3D) structures of the SARS-CoV-2 S protein (PDB ID: 6VYB, B chain) and the SARS-CoV-2 S protein RBD (PDB ID: 6M0J, B chain). It is worth noting that one epitope ( 786 QILPDPLKPTKRSFIEDLLFNKVTLA 811 ) located in the S2 subunit of the SARS-CoV S protein is an important linear B-cell epitope capable of eliciting the production of a neutralizing antibody (NAb) identified in patients who recovered from SARS-CoV infection (Table S2 ) [13] . abstract: Currently, there is limited knowledge about the immunological profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We used computer-based immunoinformatic analysis and the newly resolved 3-dimensional (3D) structures of the SARS-CoV-2 S trimeric protein, together with analyses of the immunogenic profiles of SARS-CoV, to anticipate potential B-cell and T-cell epitopes of the SARS-CoV-2 S protein for vaccine design, particularly for peptide-driven vaccine design and serological diagnosis. Nine conserved linear B-cell epitopes and multiple discontinuous B-cell epitopes composed of 69 residues on the surface of the SARS-CoV-2 trimeric S protein were predicted to be highly antigenic. We found that the SARS-CoV-2 S protein has a different antigenic profile than that of the SARS-CoV S protein due to the variations in their primary and 3D structures. Importantly, SARS-CoV-2 may exploit an immune evasion mechanism through two point mutations in the critical and conserved linear neutralization epitope (overlap with fusion peptide) around a sparsely glycosylated area. These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein. In addition, 62 T-cell epitopes in the SARS-CoV-2 S protein were predicted in our study. The structure-based immunoinformatic analysis for the SARS-CoV-2 S protein in this study may improve vaccine design, diagnosis, and immunotherapy against the pandemic of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32635180/ doi: 10.3390/vaccines8030355 id: cord-254469-7q6xi2xx author: Wang, Fuzhou title: An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development date: 2020-05-05 words: 4737.0 sentences: 245.0 pages: flesch: 48.0 cache: ./cache/cord-254469-7q6xi2xx.txt txt: ./txt/cord-254469-7q6xi2xx.txt summary: In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). However, on March 16 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US), conducted by Moderna and the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) [12, 13] . Although mRNA vaccines are commencing human clinical trials, due to the rapid global spread of this new viral pandemic, it may not be possible to develop a safe and effective vaccine for SARS-CoV-2 in time to prevent the increasing number of deaths due to this novel RNA virus. abstract: The first outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province, China, in late 2019. The subsequent COVID-19 pandemic rapidly affected the health and economy of the world. The global approach to the pandemic was to isolate populations to reduce the spread of this deadly virus while vaccines began to be developed. In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). The production of mRNA-based vaccines is a promising recent development in the production of vaccines. However, there remain significant challenges in the development and testing of vaccines as rapidly as possible to control COVID-19, which requires international collaboration. This review aims to describe the background to the rationale for the development of mRNA-based SARS-CoV-2 vaccines and the current status of the mRNA-1273 vaccine. url: https://www.ncbi.nlm.nih.gov/pubmed/32366816/ doi: 10.12659/msm.924700 id: cord-271505-eot38721 author: Wang, Hongliang title: Molecular pathogenesis of severe acute respiratory syndrome date: 2006-09-28 words: 4959.0 sentences: 229.0 pages: flesch: 48.0 cache: ./cache/cord-271505-eot38721.txt txt: ./txt/cord-271505-eot38721.txt summary: demonstrated that the angiotensin-converting enzyme 2 (ACE2) is a functional cellular receptor of SARS-CoV, by using coimmunoprecipitation of the virus glycoprotein (S1) with lysates from cells that are susceptible to virus infection (Vero E6 cells) followed by mass spectrometry analysis [7] . In the case of SARS, apoptosis was observed in patients'' lung epithelial cells; thus, SARS-CoV induced apoptosis would certainly have a deleterious pathogenic role, leading to severe tissue damage [26] . This model system allowed us to avoid possible secondary effects resulting from viral replication or infections in vivo and to directly test whether SARS-CoV spike protein might adversely affect acute lung injury through modulation of ACE2. SARS-CoV infection or spike protein treatment can down-regulate the expression of ACE2, and thus aggravate lung injury. Nabel, pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN abstract: The global outbreak in 2002–2003 of severe acute respiratory syndrome (SARS) posed a serious threat to public health and had a significant impact on socioeconomic stability. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential, and up to date, no specific treatment exists for this disease. Here we review the progress of studies on the pathogenesis of the disease, in particular, studies on the molecular level. url: https://www.ncbi.nlm.nih.gov/pubmed/17142081/ doi: 10.1016/j.micinf.2006.06.012 id: cord-260508-z11exbyu author: Wang, Hongru title: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date: 2020-10-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively. url: https://doi.org/10.1101/2020.04.20.052019 doi: 10.1101/2020.04.20.052019 id: cord-034354-4xu97je3 author: Wang, Hongye title: SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution date: 2020-10-21 words: 3678.0 sentences: 245.0 pages: flesch: 53.0 cache: ./cache/cord-034354-4xu97je3.txt txt: ./txt/cord-034354-4xu97je3.txt summary: The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. Using the SARS-CoV-2 proteome microarray, we screened IgM and IgG antibodies in the serum of 10 COVID-19 patients who were in the early stage of infection (days of symptoms onset, 3.0 ± 5.92) (Supporting Information, Table S2 ) to construct a landscape of humoral responses to the SARS-CoV-2 proteome (Figure 2 ). Sixty-one (61) IgG and IgM antibody epitopes were identified in seven SARS-CoV-2 proteins (M, N, S, Orf1ab, Orf3a, Orf7a, and Orf8) with a Z-score higher than 3 in at least one COVID-19 patient (Table 1) . Furthermore, we constructed the first landscape of B-cell epitopes of serum IgM and IgG antibodies, representing the comprehensive antibody response of COVID-19 patients to SARS-CoV-2 infection (Figures 2−4) . abstract: [Image: see text] Comprehensive profiling of humoral antibody response to severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) proteins is essential in understanding the host immunity and in developing diagnostic tests and vaccines. To address this concern, we developed a SARS-CoV-2 proteome peptide microarray to analyze antibody interactions at the amino acid resolution. With the array, we demonstrate the feasibility of employing SARS-CoV-1 antibodies to detect the SARS-CoV-2 nucleocapsid phosphoprotein. The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. With array data and structural analysis, a peptide epitope for neutralizing antibodies within the SARS-CoV-2 spike receptor-binding domain’s interaction interface with the angiotensin-converting enzyme 2 receptor was predicted. All the results demonstrate the utility of our microarray as a platform to determine the changes of antibody responses in COVID-19 patients and animal models as well as to identify potential targets for diagnosis and treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586461/ doi: 10.1021/acscentsci.0c00742 id: cord-296362-9vi8xwu7 author: Wang, Jian-Min title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function date: 2008-09-12 words: 3490.0 sentences: 199.0 pages: flesch: 57.0 cache: ./cache/cord-296362-9vi8xwu7.txt txt: ./txt/cord-296362-9vi8xwu7.txt summary: title: Construction of a non-infectious SARS coronavirus replicon for application in drug screening and analysis of viral protein function Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. Based on the infectious cDNA clone of rSARS-CoV-DE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. For in-depth study of functions of different viral proteins and regulatory sequence elements by reverse genetics, full-length infectious cDNA clones have been established using various techniques including bacterial artificial chromosome (BAC) vector [23] [24] [25] and SARS-CoV replicon cell lines [26] , which can also be used for antiviral drug screening. Construction of a severe acute respiratory syndrome coronavirus infectious cDNA clone and a replicon to study coronavirus RNA synthesis abstract: Abstract Severe acute respiratory syndrome virus (SARS-CoV) was the causative agent of the SARS outbreaks in 2002–2003. A safer in vitro system is desirable for conducting research on SARS-CoV and to screen for antiviral drugs against the virus. Based on the infectious cDNA clone of rSARS-CoV-ΔE, in which the E gene has been deleted, a safe non-infectious replicon was constructed by replacing the S gene with the enhanced green fluorescent protein (eGFP) gene. Successful replication was achieved as evident from continuous expression of eGFP detected by both fluorescence and Western blot. Treatment with antiviral drugs demonstrated that the replication could be significantly inhibited by 0.4mg/ml of cysteine proteinase inhibitor E-64D, but not by ribavirin. The same replicons containing further deletion of the coding regions for non-structural proteins (nsp) 1, 2 or 16 confirmed previous observation that nsp16, but not nsp1 or nsp2, was essential for efficient viral replication or transcription. url: https://www.sciencedirect.com/science/article/pii/S0006291X08012916 doi: 10.1016/j.bbrc.2008.06.129 id: cord-258881-74aijckl author: Wang, Maomao title: Case Report: One Case of Coronavirus Desease 2019(COVID-19) in Patient Co-nfected by HIV With a Low CD4+ T Cell Count date: 2020-04-23 words: 670.0 sentences: 45.0 pages: flesch: 64.0 cache: ./cache/cord-258881-74aijckl.txt txt: ./txt/cord-258881-74aijckl.txt summary: Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China has become an emergency of international concern When thousands of peolple were infected around the world.We report a case infected by SARS-Cov-2 and HIV simultaneously,which showed a longer course of disease and slower generation of specific antibody. Here we report a patient infected by SARS-Cov-2 , who had a relatively long course of disease with unstable state. Then eight markers of infectious diseases was checked and the result showed that abtibodies to HIV and syphilis were positive .Then the patient was transferred to specialty hospital for further treatment on March 8. People are generally susceptible to SARS-Cov-2 infection, especially the elderly patients and those with underlying diseases [2] . The author suggested that SARS-Cov-2 might damage lymphocytes, especially T lymphocytes, and the immune system was impaired during the period of disease [2] . In conclusion, we report the clinical features of a patient infected by SARS-Cov-2 and HIV. abstract: Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China has become an emergency of international concern When thousands of peolple were infected around the world.We report a case infected by SARS-Cov-2 and HIV simultaneously,which showed a longer course of disease and slower generation of specific antibody. This case highlights the coinfection of SARS-Cov-2 and HIV may impaire the immune system worse. url: https://doi.org/10.1016/j.ijid.2020.04.060 doi: 10.1016/j.ijid.2020.04.060 id: cord-297332-rzf0cw1x author: Wang, Qidi title: Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates date: 2016-04-11 words: 8688.0 sentences: 431.0 pages: flesch: 56.0 cache: ./cache/cord-297332-rzf0cw1x.txt txt: ./txt/cord-297332-rzf0cw1x.txt summary: 15 Other observations include evidence of ADE reported here for the first time induced by an inactivated SARS-CoV vaccine in rhesus macaques ( Figure 1 ) and by antisera from SARS patients (Table S1) , as well as ADE in other coronavirus infections. Herein, we discovered that a peptide of the viral sequence simultaneously elicits the antibodies of disparate functions in protection and enhancement against SARS-CoV infection by the studies with host Vero E6 cells in vitro and in non-human primates. In contrast, the immunized monkeys in the Vac3 group had a strongly increased ability to control SARS-CoV infection in association with induction of high levels of anti-S 604−625 antibodies ( Figure 7E ). 44 This study demonstrates for the first time that an antibody (mAb43-3-14) targeting a specific linear epitope (S 597−603 ) of the SARS-CoV spike protein can mediate enhancement of virus infection both in vitro and in non-human primates via an epitope sequence-dependent mechanism. abstract: [Image: see text] Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S(471–503), S(604–625), and S(1164–1191) elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S(597–603) induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S(597–603) and S(604–625)) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S(597–603) epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection. url: https://www.ncbi.nlm.nih.gov/pubmed/27627203/ doi: 10.1021/acsinfecdis.6b00006 id: cord-193489-u6ewlh16 author: Wang, Rui title: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine date: 2020-04-29 words: 6066.0 sentences: 419.0 pages: flesch: 62.0 cache: ./cache/cord-193489-u6ewlh16.txt txt: ./txt/cord-193489-u6ewlh16.txt summary: Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. Genetic identification and characterization of the geographic distribution, intercontinental evolution, and global trends of SARS-CoV-2 is the most efficient approach for studying COVID-19 genomic epidemiology and offer the molecular foundation for region-specific SARS-CoV-2 vaccine design, drug discovery, and diagnostic development [10] . We use K-means methods to cluster SARS-CoV-2 mutations, which provides the updated molecular information for the region-specific design of vaccines, drugs, and diagnoses. Table 5 presents the statistics of single mutations on various SARS-CoV-2 proteins that occurred in the recorded genomes between January 5, 2020, and April 24, 2020. Specifically, nucleocapsid protein has both the highest number of mutations per residues of 0.56 and the highest h-index of 27, suggesting that it is the most non-conservative protein in SARS-CoV-2 genomes. abstract: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs. url: https://arxiv.org/pdf/2004.14114v1.pdf doi: nan id: cord-296250-7ln7p715 author: Wang, Sheng-Fan title: The pharmacological development of direct acting agents for emerging needed therapy against severe acute respiratory syndrome coronavirus-2 date: 2020-05-20 words: 4962.0 sentences: 302.0 pages: flesch: 43.0 cache: ./cache/cord-296250-7ln7p715.txt txt: ./txt/cord-296250-7ln7p715.txt summary: Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitor. Increasing evidence reveals potential therapeutic agents acting directly against SARS-CoV-2, such as interferon (IFN), RdRp inhibitors, protease inhibitors, coronaviral protease inhibitor, viral entry blocker, neuraminidase inhibitor, vaccine, antibody, agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitors. The novel specific anti-SARS-CoV-2 agents might comprise inhibitors interfering with the viral replication cycle, antibody targeting the host receptor and virus S protein, and inhibitors of host cellular proteases involved in the virus endocytosis pathway. 33, 34 Moreover, evidence showed that diarylheptanoids, the natural products derived from Japanese alder (Alnus japonica), can inhibit the papain-like protease and restore the host innate immunity response against SARS-CoV through maintaining the function of IFNs. 31 Therefore, specific coronaviral proteases might be good candidate targets for developing new drugs to fight COVID-19. abstract: Recently, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was quickly identified as the causal pathogen leading to the outbreak of SARS-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells, and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32433345/ doi: 10.1097/jcma.0000000000000353 id: cord-354394-zojhdnlu author: Wang, Wei-Kung title: Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis date: 2004-07-17 words: 3972.0 sentences: 175.0 pages: flesch: 56.0 cache: ./cache/cord-354394-zojhdnlu.txt txt: ./txt/cord-354394-zojhdnlu.txt summary: We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis. Using a quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay and fractionation experiment, we investigated the load of SARS-CoV in these samples and different components of the throat wash. As shown in Table 1 , SARS-CoV RNA was detected in the cell-associated component of the throat wash from all 16 specimens examined. abstract: The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis. url: https://www.ncbi.nlm.nih.gov/pubmed/15324540/ doi: 10.3201/eid1007.031113 id: cord-282142-76jr4p7n author: Wang, Yun title: Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS date: 2020-08-07 words: 5495.0 sentences: 292.0 pages: flesch: 47.0 cache: ./cache/cord-282142-76jr4p7n.txt txt: ./txt/cord-282142-76jr4p7n.txt summary: Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. Therefore, the effect of SARS-CoV-2 infection on maternal and infant outcomes needs to be explored, especially the intrauterine vertical transmission potential of COVID-19. SARS-CoV infection during pregnancy was associated with a risk of adverse maternal and neonatal complications, including intrauterine growth restriction, preterm delivery, spontaneous miscarriage, severe maternal illnesses, such as, admission to the intensive care unit (ICU), renal failure, and disseminated intravascular coagulopathy, and death (4, 6, 13, (42) (43) (44) (45) (46) . The samples of amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients tested negative for SARS-CoV-2 (5), suggesting no intrauterine vertical transmission of SARS-CoV-2 in the nine pregnant COVID-19 patients. abstract: The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is highly infectious and its ongoing outbreak has been declared a global pandemic by the WHO. Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. The intrauterine vertical transmission potential of SARS-CoV-2 also remains controversial. Herein, we discuss the potential effect of COVID-19 on maternal and infant outcomes based on current studies, including those published in Chinese, in a total of 80 mothers with COVID-19 and 80 infants. We also comprehensively explored the mother-to-child transmission routes of SARS-CoV-2, in particular the route of intrauterine vertical transmission. Given SARS-CoV-2 is a sister to SARS-CoV, of the SARS-related coronavirus species, we made a comprehensive comparison between them to learn from experiences with SARS. Although there is no evidence supporting the intrauterine vertical transmission of SARS-CoV-2, our comprehensive analysis suggests that the adverse maternal and infant outcomes caused by COVID-19 cannot be underestimated. Further, we speculated that the inconsistency between nucleic acids and serological characteristics IgM to SARS-CoV-2 of infants' specimens may be caused by the disruption of the amniotic barrier by the inflammatory factors induced by SARS-CoV-2 infection. Our review is beneficial to understand the effect of SARS-CoV-2 on maternal and infant outcomes. url: https://doi.org/10.3389/fped.2020.00511 doi: 10.3389/fped.2020.00511 id: cord-333326-n9ifhw5s author: Wardell, Hanna title: Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Febrile Neonates date: 2020-07-09 words: 2919.0 sentences: 173.0 pages: flesch: 44.0 cache: ./cache/cord-333326-n9ifhw5s.txt txt: ./txt/cord-333326-n9ifhw5s.txt summary: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Herein we present a case series of 4 full-term neonates who were hospitalized with fever and found to be infected with SARS-CoV-2. Due to the concern for end-organ involvement with possibly evolving acute myocardial injury as well as a supplemental oxygen requirement, the patient was initiated on therapy with remdesivir on inpatient day 4 via an expanded-access program from the manufacturer after approval from the US Food and Drug Administration and local institutional review board, with informed consent. In this report, we present 4 febrile neonates hospitalized with SARS-CoV-2 infection with favorable outcomes. SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress abstract: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes. url: https://doi.org/10.1093/jpids/piaa084 doi: 10.1093/jpids/piaa084 id: cord-317786-iv1br2oj author: Waterfield, T. title: Seroprevalence of SARS-CoV-2 antibodies in children - A prospective multicentre cohort study. date: 2020-09-02 words: 3769.0 sentences: 271.0 pages: flesch: 54.0 cache: ./cache/cord-317786-iv1br2oj.txt txt: ./txt/cord-317786-iv1br2oj.txt summary: Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. Participants and their parents provided information at enrollment relating to age, sex, previous health and potential predictors of SARS-CoV-2 infection including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/antibody testing. Seroprevalence of SARS-CoV-2 antibodies in children of healthcare workers-A prospective multicentre cohort study protocol -Accepted for publication abstract: Background Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity and timing of testing. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection, and to report the symptomatology of infection in children. Design This multicentre observational cohort study, conducted between 16th April - 3rd July 2020 at 5 UK sites, aimed to recruit 900 children aged 2 to 15 years of age. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. Results 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10.1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariate analysis 4 independent variables were identified as significantly associated with SARS-CoV-2 infection. These were: known infected household contact; fatigue; gastrointestinal symptoms; and changes in sense of smell or taste. Discussion In this study children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. The symptoms of SARS-CoV-2 infection in children were subtle but of those reported, fatigue, gastrointestinal symptoms and changes in sense of smell or taste were most strongly associated with antibody positivity. Registration This study was registered at https://www.clinicaltrials.gov (trial registration: NCT04347408) on the 15/04/2020. url: https://doi.org/10.1101/2020.08.31.20183095 doi: 10.1101/2020.08.31.20183095 id: cord-326706-75mjs6vm author: Waterfield, Thomas title: Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study date: 2020-11-10 words: 3573.0 sentences: 242.0 pages: flesch: 49.0 cache: ./cache/cord-326706-75mjs6vm.txt txt: ./txt/cord-326706-75mjs6vm.txt summary: Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). The objective of this study was to report the presence, and titres, of SARS-CoV-2 antibodies in healthy children of healthcare workers across the UK and to report the symptomatology of infection including the asymptomatic rate. This multicentre observational prospective cohort study was designed to determine the seroprevalence of SARS-CoV-2 antibodies in healthy children, and report the symptomatology of infection. 26 Participants and their parents provided information at enrolment relating to age, sex, previous health and potential predictors of SARS-CoV-2 seropositivity including; known contact with individuals with COVID-19, contact with individuals who have been symptomatic and/or self-isolating and results of any diagnostic testing such as RT-qPCR testing/ antibody testing. abstract: BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2–15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-1 antibody positivity. TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov (trial registration: NCT0434740) on the 15 April 2020. url: https://doi.org/10.1136/archdischild-2020-320558 doi: 10.1136/archdischild-2020-320558 id: cord-258595-bk35vxlr author: Westhaus, Sandra title: Detection of SARS-CoV-2 in raw and treated wastewater in Germany – Suitability for COVID-19 surveillance and potential transmission risks date: 2020-08-18 words: 4965.0 sentences: 305.0 pages: flesch: 57.0 cache: ./cache/cord-258595-bk35vxlr.txt txt: ./txt/cord-258595-bk35vxlr.txt summary: Inoculation of differentiated Caco-2 cells for ten days with purified and concentrated wastewater (P2, P5, P11, and P12) did not result in the production of infectious SARS-CoV-2 particles (data not shown), which suggests that treated sewage appears to be non-infectious even though viral RNA fragments can be detected. Inter-comparing these nine catchment areas, we plotted the estimated cumulative and the acute prevalence against the measured SARS-CoV-2 load (Figure 8 ), the latter calculated from RT-qPCR measured M-gene copy concentration ( Figure 4 ) and the actual wastewater flow Q actual on the day of sampling (Table 2) . In contrast, plotting the incidence against SARS-CoV-2 concentration did not yield a conclusive correlation (not shown), likely because the precision of the qPCR employed was not sufficient to discriminate relatively minor differences in the incidence prevailing in the studied catchment areas at the time of sampling, ranging from 30 to 174 cases per 100,000 residents (less than an order of magnitude, Figure 8C and D). abstract: Abstract Wastewater-based monitoring of the spread of the new SARS-CoV-2 virus, also referred to as wastewater-based epidemiology (WBE), has been suggested as a tool to support epidemiology. An extensive sampling campaign, including nine municipal wastewater treatment plants, has been conducted in different cities of the Federal State of North Rhine-Westphalia (Germany) on the same day in April 2020, close to the first peak of the corona crisis. Samples were processed and analysed for a set of SARS-CoV-2-specific genes, as well as pan-genotypic gene sequences also covering other coronavirus types, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, a comprehensive set of chemical reference parameters and bioindicators was analysed to characterize the wastewater quality and composition. Results of the RT-qPCR based gene analysis indicate the presence of SARS-CoV-2 genetic traces in different raw wastewaters. Furthermore, selected samples have been sequenced using Sanger technology to confirm the specificity of the RT-qPCR and the origin of the coronavirus. A comparison of the particle-bound and the dissolved portion of SARS-CoV-2 virus genes shows that quantifications must not neglect the solid-phase reservoir. The infectivity of the raw wastewater has also been assessed by viral outgrowth assay with a potential SARS-CoV2- host cell line in vitro, which were not infected when exposed to the samples. This first evidence suggests that wastewater might be no major route for transmission to humans. Our findings draw attention to the need for further methodological and molecular assay validation for enveloped viruses in wastewater. url: https://api.elsevier.com/content/article/pii/S0048969720352797 doi: 10.1016/j.scitotenv.2020.141750 id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 words: 5066.0 sentences: 291.0 pages: flesch: 42.0 cache: ./cache/cord-264031-0y7xbgun.txt txt: ./txt/cord-264031-0y7xbgun.txt summary: title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. abstract: The recent COVID-19 pandemic has sparked a global public health crisis. Vital to the development of informed treatments for this disease is a comprehensive understanding of the molecular interactions involved in disease pathology. One lens through which we can better understand this pathology is through the network of protein-protein interactions between its viral agent, SARS-CoV-2, and its human host. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV can be explained by rapid evolution along the interface between the Spike protein and its human receptor (ACE2) leading to increased binding affinity. Sequence divergences that modulate other protein-protein interactions may further explain differences in transmission and virulence in this novel coronavirus. To facilitate these comparisons, we combined homology-based structural modeling with the ECLAIR pipeline for interface prediction at residue resolution, and molecular docking with PyRosetta. This enabled us to compile a novel 3D structural interactome meta-analysis for the published interactome network between SARS-CoV-2 and human. This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. All predictions are available online† for easy access and are continually updated when new interactions are published. † Some sections of this pre-print have been redacted to comply with current bioRxiv policy restricting the dissemination of purely in silico results predicting potential therapies for SARS-CoV-2 that have not undergone thorough peer-review. The results section titled “Prioritization of Candidate Inhibitors of SARS-CoV-2-Human Interactions Through Binding Site Comparison,” Figure 4, Supplemental Table 9, and all links to our web resource have been removed. Blank headers left in place to preserve structure and item numbering. Our full manuscript will be published in an appropriate journal following peer-review. url: https://doi.org/10.1101/2020.10.13.308676 doi: 10.1101/2020.10.13.308676 id: cord-264968-ctx39vhi author: Woo, Patrick CY title: Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia date: 2004-03-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Although the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking. METHODS: We cloned and purified the nucleocapsid protein and spike polypeptide of SARS-CoV and examined their immunogenicity with serum from patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. The seroprevalence of SARS-CoV was studied with the ELISA in healthy blood donors who donated during the SARS outbreak in Hong Kong, non-pneumonic hospital inpatients, and symptom-free health-care workers. All positive samples were confirmed by two separate western-blot assays (with recombinant nucleocapsid protein and recombinant spike polypeptide). FINDINGS: Western-blot analysis showed that the nucleocapsid protein and spike polypeptide of SARS-CoV are highly immunogenic. The specificity of the IgG antibody test (ELISA with positive samples confirmed by the two western-blot assays) was 100%, and the sensitivity was 94·3%. Three of 400 healthy blood donors who donated during the SARS outbreak and one of 131 non-pneumonic paediatric inpatients were positive for IgG antibodies, confirmed by the two western-blot assays (total, 0·48% of our study population). INTERPRETATION: Our findings support the existence of subclinical or non-pneumonic SARS-CoV infections. Such infections are more common than SARS-CoV pneumonia in our locality. url: https://www.sciencedirect.com/science/article/pii/S0140673604157292 doi: 10.1016/s0140-6736(04)15729-2 id: cord-327997-noqbcxua author: Wu, Kevin E. title: RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus date: 2020-06-20 words: 7201.0 sentences: 377.0 pages: flesch: 42.0 cache: ./cache/cord-327997-noqbcxua.txt txt: ./txt/cord-327997-noqbcxua.txt summary: We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus, and that the 5'' and 3'' viral untranslated regions contain the strongest, most distinct localization signals. As previously discussed, since much of the APEX-seq mitochondrial data used to train RNA-GPS actually consists of nuclear-encoded transcripts likely picked up as the APEX-COX4 fusion protein is transported to the mitochondria, we hypothesize that our predicted mitochondrial residency is alluding to similarity in localization pathways, rather than localization destination. To further validate the robustness of these results, we also trained a different predictive algorithm (a recurrent neural network, see STAR Methods for additional details) on the APEX-seq data and performed a similar set of experiments, comparing SARS-CoV-2 dominant subcellular residency predictions to human and coronavirus baselines ( Figure S3A /B). abstract: Abstract/Summary SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could thus play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes to the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus, and that the 5’ and 3’ viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an indicator of intracellular RNA trafficking with respect to double-membrane vesicles, a critical stage in the coronavirus life cycle. Our computational analysis serves as a hypothesis generation tool to suggest models for SARS-CoV-2 biology and inform experimental efforts to combat the virus. A record of this paper’s Transparent Peer Review process is included in the Supplemental Information. url: https://www.sciencedirect.com/science/article/pii/S2405471220302374?v=s5 doi: 10.1016/j.cels.2020.06.008 id: cord-354824-7fdcu2f0 author: Wu, Renyi title: An Update on Current Therapeutic Drugs Treating COVID-19 date: 2020-05-11 words: 9652.0 sentences: 504.0 pages: flesch: 42.0 cache: ./cache/cord-354824-7fdcu2f0.txt txt: ./txt/cord-354824-7fdcu2f0.txt summary: Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. This estimated 20% of patients developing more severe disease with SARS-CoV-2 infection are most likely due to genetics, epigenetics, and or other factors, with dampened innate immune response to fight the virus coupled with enhanced viral load leading to cytokine storm, severe inflammatory/oxidative stress response, and severe lung injury secondary to ARDS. Chloroquine can inhibit the entry of SARS-CoV-2 and prevent virus-cell fusion by interfering with glycosylation of ACE2 receptor and its binding with spike protein, suggesting that chloroquine treatment might be more effective in the early stage of infection, before COVID-19 reduces ACE2 expression and activity [30, 38, 39] . Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, doubleblinded, phase IIb clinical trial (CloroCovid-19 Study) abstract: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2. url: https://doi.org/10.1007/s40495-020-00216-7 doi: 10.1007/s40495-020-00216-7 id: cord-271243-8cfyen86 author: Xiao, Y. title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus date: 2008-05-31 words: 3375.0 sentences: 179.0 pages: flesch: 52.0 cache: ./cache/cord-271243-8cfyen86.txt txt: ./txt/cord-271243-8cfyen86.txt summary: title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). The present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. One animal from each group was sacrificed at 3, 13, 23, 34 and 35 days post-infection (dpi), and lung, spleen, lymph node, small intestine, kidney, trachea, cerebrum, pancreas, sex glands, stomach and heart were collected from each animal. In summary, the data presented in this study further corroborate previous findings (Wu et al., 2005) in demonstrating that civets are more susceptible to SARS-CoV infection than other animals, as implied by their clinical symptoms, pathological changes and virus distribution within tissues. abstract: Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). Infected animals become less aggressive and develop pyrexia, lethargy and diarrhoea. The present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. In-situ hybridization (ISH) with probes specific for the RNA polymerase gene demonstrated viral RNA in the lung, small intestine and cerebrum only. In-situ labelling was employed in order to demonstrate cellular apoptosis in the cerebrum, but there was no evidence of apoptosis within the myocardium. These results indicate that SARS-CoV causes multi-organ pathology in civets, similar to that observed in human SARS patients. These parallels suggest that civets may be used as an animal model of this infection to gain insight into the pathogenesis of SARS and for evaluation of candidate vaccines and antiviral drugs. url: https://www.ncbi.nlm.nih.gov/pubmed/18343398/ doi: 10.1016/j.jcpa.2007.12.005 id: cord-321918-9jwma2y6 author: Xiu, Siyu title: Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities date: 2020-06-15 words: 10526.0 sentences: 621.0 pages: flesch: 52.0 cache: ./cache/cord-321918-9jwma2y6.txt txt: ./txt/cord-321918-9jwma2y6.txt summary: The spike protein can be divided into two domains; S1 is responsible for angiotensin-converting enzyme II(ACE2) recognition, the recently identified host cell receptor, and S2 mediates membrane fusion (Figure 2 ). 98 99 On the basis of this approach, they identified two small molecules, TGG (12, Table 4 ) and luteolin (13) , that can bind avidly to the SARS-CoV S2 protein and inhibit viral entry of SARS-CoV into Vero E6 cells with IC 50 values of 4.5 and 10.6 μM, respectively. 113 A high-throughput screen (HTS) of a 1000-compound library that resulted in the identification of MDL28170 (17 , Table 4 ) by Bates et al., and in an antiviral activity assay, 17 specifically inhibited cathepsin L-mediated substrate cleavage and blocked SARS-CoV viral entry, with an IC 50 value of 2.5 nM and EC 50 value in the range of 100 nM. abstract: [Image: see text] Recently, a novel coronavirus initially designated 2019-nCoV but now termed SARS-CoV-2 has emerged and raised global concerns due to its virulence. SARS-CoV-2 is the etiological agent of “coronavirus disease 2019”, abbreviated to COVID-19, which despite only being identified at the very end of 2019, has now been classified as a pandemic by the World Health Organization (WHO). At this time, no specific prophylactic or postexposure therapy for COVID-19 are currently available. Viral entry is the first step in the SARS-CoV-2 lifecycle and is mediated by the trimeric spike protein. Being the first stage in infection, entry of SARS-CoV-2 into host cells is an extremely attractive therapeutic intervention point. Within this review, we highlight therapeutic intervention strategies for anti-SARS-CoV, MERS-CoV, and other coronaviruses and speculate upon future directions for SARS-CoV-2 entry inhibitor designs. url: https://doi.org/10.1021/acs.jmedchem.0c00502 doi: 10.1021/acs.jmedchem.0c00502 id: cord-338973-73a7uvyz author: Xu, Jiabao title: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date: 2020-02-22 words: 7110.0 sentences: 426.0 pages: flesch: 57.0 cache: ./cache/cord-338973-73a7uvyz.txt txt: ./txt/cord-338973-73a7uvyz.txt summary: After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections. abstract: After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/32098422/ doi: 10.3390/v12020244 id: cord-348821-2u6ki9dv author: Xu, Ping title: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. date: 2020-03-10 words: 3329.0 sentences: 209.0 pages: flesch: 51.0 cache: ./cache/cord-348821-2u6ki9dv.txt txt: ./txt/cord-348821-2u6ki9dv.txt summary: The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases. https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection abstract: After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon. url: https://doi.org/10.1101/2020.03.08.20032821 doi: 10.1101/2020.03.08.20032821 id: cord-306373-61snvddh author: Xu, Xiao-Wei title: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series date: 2020-02-19 words: 3594.0 sentences: 204.0 pages: flesch: 56.0 cache: ./cache/cord-306373-61snvddh.txt txt: ./txt/cord-306373-61snvddh.txt summary: OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). Since the outbreak of covid-19, strict precautionary measures have been implemented in Zhejiang province, including the creation of fever clinics that exclusively receive patients with suspected SARS-Cov-2 infection, defined as presenting with a fever or any respiratory symptoms, including dry cough, and especially in those with a history of travel to Wuhan or exposure to infected people within two weeks before the onset of illness since January 2020. The incubation period was defined as the time from exposure to the onset of illness, which was estimated among patients who could provide the exact date of close contact with individuals from Wuhan with confirmed or suspected SARS-Cov-2 infection. abstract: OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild. url: https://doi.org/10.1136/bmj.m606 doi: 10.1136/bmj.m606 id: cord-032222-i6gfp4me author: Xue, Ling title: A quick look at the latest developments in the COVID-19 pandemic date: 2020-09-10 words: 2867.0 sentences: 206.0 pages: flesch: 49.0 cache: ./cache/cord-032222-i6gfp4me.txt txt: ./txt/cord-032222-i6gfp4me.txt summary: Later, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses formally named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a novel coronavirus, and an effective vaccine has yet to be developed. 51 A recombinant adenovirus type 5 vector vaccine, developed by Chen Wei''s team, showed good safety and immunogenicity in a phase I clinical trial, rapidly inducing both humoral and T-cell responses against SARS-CoV-2 in most participants. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia abstract: In December 2019, a new respiratory disease manifesting as viral pneumonia emerged in Wuhan, China. Isolation and identification of the virus showed that the pathogen causing this disease was a novel coronavirus. On January 12, 2020, the World Health Organization named the novel coronavirus causing the outbreak 2019 novel coronavirus (2019-nCoV). The disease caused by the virus was named coronavirus disease 2019 (COVID-19). Later, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses formally named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus shows strong infectivity and high lethality, arousing widespread concern. As an emerging virus, a comprehensive understanding of SARS-CoV-2 is missing. To provide a reference and a theoretical basis for further study of SARS-CoV-2, recent advances in our understanding of the virus are summarized in this review. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488894/ doi: 10.1177/0300060520943802 id: cord-352562-qfb478sf author: Yamamoto, Lidia title: SARS-CoV-2 infections with emphasis on pediatric patients: a narrative review date: 2020-09-04 words: 7315.0 sentences: 341.0 pages: flesch: 45.0 cache: ./cache/cord-352562-qfb478sf.txt txt: ./txt/cord-352562-qfb478sf.txt summary: In the section devoted to the specific laboratory diagnosis of COVID-19, the most used RT-PCR protocols were described and some studies on the serological diagnosis with IgA, IgM and IgG detection were detailed, including the use of rapid immunochromatographic assays and discussing the ideal period after the onset of symptoms to perform each type of test. They identified 191 cases in hospitalized patients younger than 21 years of age, reported by hospitals in the New York State with the diagnosis of Kawasaki disease, toxic shock syndrome, myocarditis, and suspected multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The laboratory diagnosis of COVID-19 are based on the detection of viral RNA by real time amplifications (RT-PCR) 40 or the detection of antibodies (immunoglobulins) anti-SARS-CoV-2 from the classes IgM, IgA and IgG, produced by the host''s immune system. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review abstract: This narrative review summarizes the main aspects underlying the new coronavirus SARS-CoV-2, its epidemiology, pathophysiology, pointing to differences of SARS-CoV-2 main receptors ACE2, in terms of expression and the amount of soluble ACE2 in the circulation of children, men and women, and also in those with risk factors such as the smokers and pregnant women or presenting with comorbidities (diabetes, obesity, hypertension and other cardiovascular diseases, renal and CNS pre-existing diseases). Clinical manifestations in adults and children were also described, emphasizing the particularities already seen in children, regarding signs, symptoms, viral excretion time and the involvement of all organs and systems. The COVID-19 in the pediatric population was divided into two sections: one dedicated to previously healthy children and adolescents with COVID-19, and the other to those who live with comorbidities and acquired COVID-19. A few paragraphs were reserved to the recently described severe multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) that shares certain characteristics with Kawasaki disease. Some studies on the infection in pregnant and postpartum women, as well as neonates were shown. This review has also covered the laboratory diagnosis of COVID-19, passing through the imaging diagnosis made by the chest tomography revealing ground glass patching opacities, and results of non-specific exams such as the total blood with lymphopenia, the coagulation tests with increased prothrombin times, as well as marked increments of the D-dimer, troponin and proinflammatory cytokines. In the section devoted to the specific laboratory diagnosis of COVID-19, the most used RT-PCR protocols were described and some studies on the serological diagnosis with IgA, IgM and IgG detection were detailed, including the use of rapid immunochromatographic assays and discussing the ideal period after the onset of symptoms to perform each type of test. In the end, the management of pediatric patients with COVID-19 based mainly on supportive measures has been briefly commented. url: https://doi.org/10.1590/s1678-9946202062065 doi: 10.1590/s1678-9946202062065 id: cord-267887-ntwvquqz author: Yang, Ren title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro date: 2020-08-21 words: 1308.0 sentences: 81.0 pages: flesch: 51.0 cache: ./cache/cord-267887-ntwvquqz.txt txt: ./txt/cord-267887-ntwvquqz.txt summary: title: Development and effectiveness of Pseudotyped SARS-CoV-2 system as determined by neutralizing efficiency and entry inhibition test in vitro Previously, researchers had developed a pseudotyped virus system for SARS-CoV and MERS-CoV, based on HIV-1 core, bearing virus spike protein. Furthermore, the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples from convalescent patients. In conclusion, we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory. Development and optimization of a sensitive pseudovirus-based assay for HIV-1 neutralizing antibodies detection using A3R5 cells A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig abstract: With the development of the COVID-19 epidemic, there is an urgent need to establish a system for determining the effectiveness and neutralizing activity of vaccine candidates in biosafety level 2 (BSL-2) facilities. Previously, researchers had developed a pseudotyped virus system for SARS-CoV and MERS-CoV, based on HIV-1 core, bearing virus spike protein. During the development of a pseudotyped SARS-CoV-2 system, a eukaryotic expression plasmid expressing SARS-CoV-2 spike (S) protein was constructed and then co-transfected with HIV-1 based plasmid which containing the firefly luciferase reporter gene, into HEK293T cells to prepare the pseudotyped SARS-CoV-2 virus (ppSARS-2). We have successfully established the pseudotyped SARS-CoV-2 system for neutralization and entry inhibition assays. Huh7.5 cell line was found to be the most susceptible to our pseudotyped virus model. Different levels of neutralizing antibodies were detected in convalescent serum samples of COVID-19 patients using ppSARS-2. The recombinant, soluble, angiotensin-converting enzyme 2 protein was found to inhibit the entry of ppSARS-2 in Huh7.5 cells effectively. Furthermore, the neutralization results for ppSARS-2 were consistent with those of live SARS-CoV-2 and determined using the serum samples from convalescent patients. In conclusion, we have developed an easily accessible and reliable tool for studying the neutralizing efficiency of antibodies against SARS-CoV-2 and the entry process of the virus in a BSL-2 laboratory. url: https://www.sciencedirect.com/science/article/pii/S2590053620300884?v=s5 doi: 10.1016/j.bsheal.2020.08.004 id: cord-327690-di7hfghi author: Yang, Xiaobo title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study date: 2020-02-24 words: 3848.0 sentences: 241.0 pages: flesch: 53.0 cache: ./cache/cord-327690-di7hfghi.txt txt: ./txt/cord-327690-di7hfghi.txt summary: title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. In this study, we investigated critically ill patients with confirmed SARS-CoV-2 pneumonia who were admitted to Wuhan Jin Yin-tan hospital. The baseline SARS-CoV-2-associated morbidity and mortality data from this study will be of considerable value for the early identification of individuals who are at risk of becoming critically ill and who are most likely to benefit from intensive care treatment. During the outbreak of SARS-CoV-2 infection, the number of critically ill patients exceeded the capacity of ICUs. Therefore, two provisional ICUs were urgently established in Jin Yin-tan hospital and hence most mechanical ventilator settings and recordings were not recorded, except records of positive end-expiratory pressure in some cases. abstract: BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None. url: https://www.sciencedirect.com/science/article/pii/S2213260020300795 doi: 10.1016/s2213-2600(20)30079-5 id: cord-351525-306syrrn author: Yang, Yong-Le title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission date: 2019-11-26 words: 6911.0 sentences: 306.0 pages: flesch: 53.0 cache: ./cache/cord-351525-306syrrn.txt txt: ./txt/cord-351525-306syrrn.txt summary: title: Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. As a brief summary of the results, 21 of the 24 cell lines showed significant susceptibility to SADS-CoV infection, defined by efficient viral replication, antigen expression, and the appearance of cytopathic effect (CPE). As some cells did not display CPE after SADS-CoV infection, all cell lines were subsequently tested for viral M protein expression by immunofluorescence assay (IFA) Fig. 1) , revealing the same range as seen by CPE in the different cell lines (data not shown). abstract: Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species Rhinolophus bat coronavirus HKU2 (Y. Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15–21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255–258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV in vitro and in vivo. We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation in vitro. Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers. IMPORTANCE Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV [SARS-CoV] and Middle East respiratory syndrome CoV [MERS-CoV]) have caused severe illness in humans after “host jump” events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An in vitro susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV. url: https://doi.org/10.1128/jvi.01448-19 doi: 10.1128/jvi.01448-19 id: cord-253457-gawn4s9g author: Yau, Kevin title: COVID-19 Outbreak in an Urban Hemodialysis Unit date: 2020-07-15 words: 2215.0 sentences: 145.0 pages: flesch: 47.0 cache: ./cache/cord-253457-gawn4s9g.txt txt: ./txt/cord-253457-gawn4s9g.txt summary: Patients with SARS-CoV-2 infection including asymptomatic individuals were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR testing. Nasopharyngeal swabs were performed by physicians, nurse practitioners, and staff from the hospital''s COVID-19 Assessment Centre under droplet and contact precautions in the hemodialysis unit with curtains drawn around the dialysis station at which the patient was being swabbed. At the time of testing, six (55%) patients and six (55%) staff positive for SARS-CoV-2 were asymptomatic. Patients with confirmed SARS-CoV-2 infection including asymptomatic individuals were dialyzed in a dedicated room separate from the main hemodialysis unit for the duration of their infection and maintained on droplet and contact precautions. Five hemodialysis staff were allowed to return to work following symptom resolution and documentation of two negative SARS-CoV-2 nasopharyngeal swabs performed 14 days from symptom onset. Infection control authorities concluded that SARS-CoV-2 transmission during an outbreak at the St. Michael''s Hospital hemodialysis unit was likely to have originated from two index cases. abstract: RATIONALE & OBJECTIVE: Hemodialysis patients are at increased risk for COVID-19 transmission due, in part, to difficulty maintaining physical distancing. Our hemodialysis unit experienced a COVID-19 outbreak despite following symptom-based screening guidelines. We describe the course of the COVID-19 outbreak and the infection control measures taken for mitigation. STUDY DESIGN: Retrospective cohort study SETTING & PARTICIPANTS: 237 maintenance hemodialysis patients and 93 hemodialysis staff at a single hemodialysis centre in Toronto, Canada. EXPOSURE: Universal screening of patients and staff with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OUTCOMES: The primary outcome was detection of SARS-CoV-2 in nasopharyngeal samples from patients and staff using reverse transcriptase-polymerase chain reaction (RT-PCR) . ANALYTICAL APPROACH: Descriptive statistics were used for clinical characteristics and the primary outcome. RESULTS: Eleven (4.6%) of 237 hemodialysis patients and 11 of 93 (12%) staff members had a positive RT-PCR test for SARS-CoV-2. Among individuals testing positive, 12 of 22 (55%) were asymptomatic at time of testing, and 7 of 22 (32%) were asymptomatic for the duration of follow-up. One patient was hospitalized at the time of SARS-CoV-2 infection and four additional patients with positive tests were subsequently hospitalized. Two patients (18%) required admission to the intensive care unit. After 30 days follow-up no patients had died or required mechanical ventilation. No hemodialysis staff required hospitalization. Universal droplet and contact precautions were implemented during the outbreak. Hemodialysis staff with SARS-CoV-2 infection were placed on home quarantine regardless of symptom status. Patients with SARS-CoV-2 infection including asymptomatic individuals were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR testing. Analysis of the outbreak identified two index cases with subsequent nosocomial transmission within the dialysis unit and in shared shuttle buses to the hemodialysis unit. LIMITATIONS: Single centre study. CONCLUSIONS: Universal SARS-CoV-2 testing and universal droplet and contact precautions in the setting of an outbreak appeared to be effective in preventing further transmission. url: https://api.elsevier.com/content/article/pii/S0272638620308118 doi: 10.1053/j.ajkd.2020.07.001 id: cord-353704-lfndq85x author: Ye, Zi-Wei title: Zoonotic origins of human coronaviruses date: 2020-03-15 words: 8096.0 sentences: 434.0 pages: flesch: 54.0 cache: ./cache/cord-353704-lfndq85x.txt txt: ./txt/cord-353704-lfndq85x.txt summary: In contrast, SARS-CoV, MERS-CoV and the newly-identified SARS-CoV-2 are highly pathogenic, causing severe lower respiratory tract infection in relatively more patients with a higher chance to develop acute respiratory distress syndrome (ARDS) and extrapulmonary manifestations. The 2019 novel HCoV (2019-nCoV), which has subsequently been renamed SARS-CoV-2, is the causative agent of the ongoing epidemic of coronavirus disease 2019 (COVID19) , which has claimed more than 3,120 lives and infected more than 91,000 people as of March 3, 2020 [19] . All these four communityacquired HCoVs have been well adapted to humans and are generally less likely to mutate to cause highly pathogenic diseases, though accidents did occur for unknown reasons as in the rare case of a more virulent subtype of HCoV-NL63, which has recently been reported to cause severe lower respiratory tract infection in China [38] . Alternatively, whereas bat alpha-CoVs serve as the gene pool of HCoV-229E, alpacas and dromedary camels might serve as intermediate hosts that transmit viruses to humans, exactly as in the case of MERS-CoV [69] . abstract: Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted. url: https://www.ncbi.nlm.nih.gov/pubmed/32226286/ doi: 10.7150/ijbs.45472 id: cord-253844-y6xdcf20 author: Yesudhas, Dhanusha title: COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics date: 2020-09-04 words: 7165.0 sentences: 422.0 pages: flesch: 51.0 cache: ./cache/cord-253844-y6xdcf20.txt txt: ./txt/cord-253844-y6xdcf20.txt summary: In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. The sequence similarity between SARS-CoV-2 and SARS-CoV spike proteins explains the possibility of binding to the same receptor angiotensin converting enzyme 2 (ACE2) in the host cell [14] . In this review, we discuss the history of coronaviruses in both humans and animals, their transmissions, mechanism of host cell entry and the structural studies, explaining active and inactive receptor binding of spike protein and the key residues playing an important role in the receptor binding. During viral infection, spike protein (~ 1300 amino acid residues) is cleaved by host proteases into receptor binding subunit S1 and membrane fusion subunit S2. abstract: PURPOSE: The coronavirus outbreak emerged as a severe pandemic, claiming more than 0.8 million lives across the world and raised a major global health concern. We survey the history and mechanism of coronaviruses, and the structural characteristics of the spike protein and its key residues responsible for human transmissions. METHODS: We have carried out a systematic review to summarize the origin, transmission and etiology of COVID-19. The structural analysis of the spike protein and its disordered residues explains the mechanism of the viral transmission. A meta-data analysis of the therapeutic compounds targeting the SARS-CoV-2 is also included. RESULTS: Coronaviruses can cross the species barrier and infect humans with unexpected consequences for public health. The transmission rate of SARS-CoV-2 infection is higher compared to that of the closely related SARS-CoV infections. In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. The key residues of the spike protein have stronger binding affinity with ACE2. These can be probable reasons for the higher transmission rate of SARS-CoV-2. In addition, we have also discussed the therapeutic compounds and the vaccines to target SARS-CoV-2, which can help researchers to develop effective drugs/vaccines for COVID-19. SUMMARY: The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs. url: https://doi.org/10.1007/s15010-020-01516-2 doi: 10.1007/s15010-020-01516-2 id: cord-289598-t8upoq9a author: Yoon, Jane C title: COVID-19 Prevalence among People Experiencing Homelessness and Homelessness Service Staff during Early Community Transmission in Atlanta, Georgia, April–May 2020 date: 2020-09-08 words: 2980.0 sentences: 197.0 pages: flesch: 56.0 cache: ./cache/cord-289598-t8upoq9a.txt txt: ./txt/cord-289598-t8upoq9a.txt summary: BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7–May 6, 2020. Risk of SARS-CoV-2 infection, the virus that causes COVID-19, may be higher among people experiencing homelessness (PEH) because of challenges in preventing respiratory disease transmission in congregate shelter settings. Our finding of decreased prevalence in four shelters during repeat testing is consistent with reports from skilled nursing facilities and correctional facilities, supporting the use of universal (facility-wide) testing for early identification and isolation of those with positive SARS-CoV-2 as a strategy to interrupt transmission in congregate settings [23] [24] [25] . abstract: BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7–May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire RESULTS: Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%–27.6%. Repeat testing 3–4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%–3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response CONCLUSIONS: PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission url: https://doi.org/10.1093/cid/ciaa1340 doi: 10.1093/cid/ciaa1340 id: cord-282058-it0ojdk3 author: Yu, Yuanqiang title: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review date: 2020-05-15 words: 7461.0 sentences: 389.0 pages: flesch: 50.0 cache: ./cache/cord-282058-it0ojdk3.txt txt: ./txt/cord-282058-it0ojdk3.txt summary: References for this review were identified through searches of PubMed for articles published from January 1, 2003, to May 1, 2020, by use of the terms "coronavirus, " "neonate, " "children, " "COVID19, " and "SARS-CoV-2." Relevant articles published between 2003 and 2020 were identified through searches in the authors'' personal files. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The symptoms of COVID-19 appear to be less severe in infants and children than in adult patients, similar to the SARS-CoV infection (15) (16) (17) . Of the 34 pregnant women who were confirmed with the SARS-CoV-2 infection in multiple hospitals in Wuhan, including one pregnant woman with a negative nucleic acid test result, 30 had a fever and 16 had a cough (54) (55) (56) (57) . abstract: At the end of 2019, a novel coronavirus began to spread in Wuhan, Hubei Province, China. The confirmed cases increased nationwide rapidly, in part due to the increased population mobility during the Chinese Lunar New Year festival. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Soon, transmission from person to person was confirmed and the virus spread to many other countries. To date, many cases have been reported in the pediatric age group, most of which were from China. The management and treatment strategies have also been improved, which we believe would be helpful to pediatric series in other countries as well. However, the characteristics of neonatal and childhood infection still have not been evaluated in detail. This review summarizes the current understanding of SARS-CoV-2 infection in neonates and children from January 24 to May 1, as an experience from China. url: https://www.ncbi.nlm.nih.gov/pubmed/32574286/ doi: 10.3389/fped.2020.00287 id: cord-342902-y1v8wzxq author: Yuan, Shuofeng title: Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters date: 2020-10-07 words: 5692.0 sentences: 291.0 pages: flesch: 45.0 cache: ./cache/cord-342902-y1v8wzxq.txt txt: ./txt/cord-342902-y1v8wzxq.txt summary: Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. We found that co-application of clofazimine and remdesivir impacts SARS-CoV-2 replication in a manner that extends beyond the additive combinatorial activity predicted by the Bliss independence model (maximal Bliss Synergy Score of 44.28; Figure 5a , Extended Data Figure 2) , and indicates these two drugs harbor a synergistic antiviral relationship. abstract: COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting multiple underlying antiviral mechanisms. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Additionally, clofazimine exhibited synergy when administered with remdesivir. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoVs of the future. url: https://doi.org/10.21203/rs.3.rs-86169/v1 doi: 10.21203/rs.3.rs-86169/v1 id: cord-258268-7ypq0t3d author: Zanin, Luca title: SARS-CoV-2 can induce brain and spine demyelinating lesions date: 2020-05-04 words: 1481.0 sentences: 113.0 pages: flesch: 47.0 cache: ./cache/cord-258268-7ypq0t3d.txt txt: ./txt/cord-258268-7ypq0t3d.txt summary: On January 24, 2020, a new virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been identified, quickly gaining worldwide attention [21] . Similarly to other Coronavirus, SARS-CoV-2 can attack the olfactory bulb and then affect the central nervous system (CNS) through the olfactory tract in the early stages of infection [5] . Neurological impairment and demyelinating reaction appear as complications in case of severe Coronavirus Disease 2019 (COVID-19) [10] . Our patient showed symptoms consistent with a neurological involvement consequent to SARS-CoV-2 infection. In SARS-CoV-2 infection, neurological impairment was observed only in case of severe COVID-19 [10] . SARS-CoV-2 was not detected in the CSF probably because the neurological damage was sustained by a delayed immune response that occurred after the viremia. Sudden neurological impairment with seizures in COVID-19 patients may be sustained by CNS involvement and demyelinating lesions. Neurologic features in severe SARS-CoV-2 infection abstract: SARS-CoV-2 can attack the central nervous system in the early stages of infection. Headache, anosmia, and dysgeusia are common symptoms. Disturbance of consciousness and seizures can occur as complications in case of severe COVID-19. We described the case of a COVID-19 patient admitted for interstitial pneumonia and seizures. MRI showed newly diagnosed demyelinating lesions. High-dose steroid treatment allowed neurological and respiratory recovery. We speculated a delayed immune response induced by SARS-CoV-2. The virus may lead to a SIRS-like immune disorder or play a role of infective trigger. Prompt invasive treatment should be adopted to avoid hypoxic neurotoxicity and prevent CNS injuries. url: https://doi.org/10.1007/s00701-020-04374-x doi: 10.1007/s00701-020-04374-x id: cord-338243-njkhwkwk author: Zhang, Dayi title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital date: 2020-06-23 words: 2831.0 sentences: 158.0 pages: flesch: 51.0 cache: ./cache/cord-338243-njkhwkwk.txt txt: ./txt/cord-338243-njkhwkwk.txt summary: title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of Fangcang Hospital In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Cabin Hospital and found a striking high level of (0.5–18.7) × 103 copies/L after disinfection with sodium hypochlorite. In septic tanks, disinfection achieved free chlorine > 6.5 mg/L for 1.5 hours when the dosage of sodium hypochlorite was 800 g/m 3 , meeting well with the guideline for emergency treatment of medical sewage containing SARS-CoV-2 suggested by China CDC. Septic tanks can behave as a long-term source J o u r n a l P r e -p r o o f to release SARS-CoV-2 viral RNA into waters when disinfection is not sufficient and challenges public health via potentially spreading viruses in drainage pipelines. abstract: Abstract The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia raises the concerns of effective deactivation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in medical wastewater by disinfectants. In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Cabin Hospital and found a striking high level of (0.5–18.7) × 103 copies/L after disinfection with sodium hypochlorite. Embedded viruses in stool particles might be released in septic tanks, behaving as a secondary source of SARS-CoV-2 and potentially contributing to its spread through drainage pipelines. Current recommended disinfection strategy (free chlorine ≥0.5 mg/L after at least 30 min suggested by World Health Organization; free chlorine above 6.5 mg/L after 1.5-h contact by China Centers for Disease Control and Prevention) needs to be reevaluated to completely remove SARS-CoV-2 viral RNA in non-centralized disinfection system and effectively deactivate SARS-CoV-2. The effluents showed negative results for SARS-CoV-2 viral RNA when overdosed with sodium hypochlorite but had high a level of disinfection by-product residuals, possessing significant ecological risks. url: https://doi.org/10.1016/j.scitotenv.2020.140445 doi: 10.1016/j.scitotenv.2020.140445 id: cord-293082-fw7deem8 author: Zhang, Guangzhi title: Animal coronaviruses and SARS‐CoV‐2 date: 2020-08-16 words: 2068.0 sentences: 157.0 pages: flesch: 48.0 cache: ./cache/cord-293082-fw7deem8.txt txt: ./txt/cord-293082-fw7deem8.txt summary: As of April 7, just four months since its first outbreak, more 48 than 3.4 million confirmed cases and 238,000 deaths have been recorded in 215 countries, areas, 49 and territories, and moreover it seems that severe acute respiratory syndrome coronavirus 2 50 (SARS-CoV-2) that causes COVID-19 will probably continue to circulate around the globe 51 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The health 52 authorities and governments of affected countries have paid attention to current pandemic and 53 have taken immediate measures to block COVID-19 transmission, including utilization of personal 54 protective equipment, quarantine, epidemiological investigation, isolation, clinical data analysis 55 and sharing, public health education, maintaining social distance, the creation of diagnostics, 56 therapeutics, and vaccines, etc (Xiao and Torok 2020) . Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain abstract: COVID‐19 is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has rapidly spread to 216 countries and territories since first outbreak in December of 2019, posing a substantial economic losses and extraordinary threats to the public health worldwide. Although bats have been suggested as the natural host of SARS‐CoV‐2, transmission chains of this virus, role of animals during cross‐species transmission, and future concerns remain unclear. Diverse animal coronaviruses have extensively been studied since the discovery of avian coronavirus in 1930s. The current article comprehensively reviews and discusses the current understanding about animal coronaviruses and SARS‐CoV‐2 for their emergence, transmission, zoonotic potential, alteration of tissue/host tropism, evolution, status of vaccines, and surveillance. This study aims at providing guidance for control of COVID‐19 and preventative strategies for possible future outbreaks of zoonotic coronavirus via cross‐species transmission. url: https://doi.org/10.1111/tbed.13791 doi: 10.1111/tbed.13791 id: cord-294831-pem059zk author: Zhang, Ling-Pu title: Focus on a 2019-novel coronavirus (SARS-CoV-2) date: 2020-06-11 words: 6173.0 sentences: 378.0 pages: flesch: 54.0 cache: ./cache/cord-294831-pem059zk.txt txt: ./txt/cord-294831-pem059zk.txt summary: A report of five patients in a family cluster who traveled to Wuhan and were infected with SARS-CoV-2 was the first report directly illustrating that the virus is capable of person-to-person transmission in hospital and family settings [23] . Xiao and colleagues showed that 53.42% of 73 hospitalized COVID-19 patients had SARS-CoV-2 RNA in stool specimens, and the duration time of positive stool results ranged from 1 to 12 days [27] . In a study published in The Lancet, 41 of 41 patients who were identified as positive for SARS-CoV-2 infection presented with pneumonia and abnormal chest computed tomography (CT) [6] . An article reported in Science shows that SARS-CoV-2 can replicate in the upper respiratory tract of ferrets, indicating that ferrets represent an ideal animal model for evaluating antiviral drugs or vaccine candidates against COVID-19 [64] . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan abstract: A new coronavirus, severe acute respiratory syndrome coronavirus 2, was first discovered in Wuhan, China, in December 2019. As of April 7, 2020, the new coronavirus has spread quickly to 184 countries and aroused the attention of the entire world. No targeted drugs have yet been available for intervention and treatment of this virus. The sharing of academic information is crucial to risk assessment and control activities in outbreak countries. In this review, we summarize the epidemiological, genetic and clinical characteristics of the virus as well as laboratory testing and treatments to understand the nature of the virus. We hope this review will be helpful to prevent viral infections in outbreak countries and regions. url: https://doi.org/10.2217/fmb-2020-0063 doi: 10.2217/fmb-2020-0063 id: cord-261075-wqtxhiy8 author: Zhang, Meng title: The nervous system——a new territory being explored of SARS-CoV-2 date: 2020-10-28 words: 3716.0 sentences: 216.0 pages: flesch: 41.0 cache: ./cache/cord-261075-wqtxhiy8.txt txt: ./txt/cord-261075-wqtxhiy8.txt summary: However, there is growing evidence that SARS-CoV-2 can result in a broad spectrum of neurologic diseases (6) (7) (8) (9) , which is not surprising, as neurological manifestations have been reported in other respiratory viral infections, including coronavirus, but the nervous system manifestations of COVID-19 are more common and disabling, raising the worldwide concerns about its potential long-term complications to humans (10, 11) . In particular, we focused on its neurological manifestations and specific pathogenesis, as well as its comparison with other viral respiratory infections.Finally, we further summarized the significance of the neuroinvasion and the follow-up issues that need to be paid attention to by scientists, so as to help neurologists understand the influence of SARS-CoV-2 on nervous system better and promote the accurate diagnosis and efficient treatment of COVID-19. abstract: In December 2019, COVID-19 outbroke in Wuhan, then sweeping the mainland of China and the whole world rapidly. On March 4, Beijing Ditan Hospital confirmed the existence of SARS-CoV-2 in the cerebrospinal fluid by gene sequencing, indicating the neurotropic involvement of SARS-CoV-2. Meanwhile, neurological manifestations in the central nervous system, peripheral nervous system and skeletal muscular were also observed, indicating the potential neuroinvasion of SARS-CoV-2. In particular, we focused on its neurological manifestations and specific pathogenesis, as well as its comparison with other viral respiratory infections.Finally, we further summarized the significance of the neuroinvasion and the follow-up issues that need to be paid attention to by scientists, so as to help neurologists understand the influence of SARS-CoV-2 on nervous system better and promote the accurate diagnosis and efficient treatment of COVID-19. url: https://api.elsevier.com/content/article/pii/S0967586820316155 doi: 10.1016/j.jocn.2020.10.056 id: cord-254968-czrgzyr3 author: Zhang, Qiang title: A serological survey of SARS-CoV-2 in cat in Wuhan date: 2020-09-17 words: 3148.0 sentences: 180.0 pages: flesch: 56.0 cache: ./cache/cord-254968-czrgzyr3.txt txt: ./txt/cord-254968-czrgzyr3.txt summary: Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19. Here, we investigated the serological prevalence of SARS-CoV-2 in cats by an indirect ELISA and virus neutralization tests (VNT), and monitored the serum antibody dynamics of cats infected SARS-CoV-2, providing a basis for further understanding the infection of SARS-CoV-2 in cats. In this study, we detected the presence of SARS-CoV-2 antibodies in cats in Wuhan during the COVID-19 outbreak with ELISA, VNT and western blot. Virus neutralization test and Western blot assay of cat serum samples for SARS-CoV-2 (A) Cat#14, Cat#15 and Cat#4 sera were 3-fold serially diluted and mixed with SARS-CoV-2; after incubated at 37°C for 1 h, the mixture was used to infect Vero E6 cells, and replaced with semi-solid media 1 h later. abstract: COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19. url: https://doi.org/10.1080/22221751.2020.1817796 doi: 10.1080/22221751.2020.1817796 id: cord-316126-j51dik7f author: Zhang, X. Sophie title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles date: 2020-10-28 words: 12434.0 sentences: 576.0 pages: flesch: 42.0 cache: ./cache/cord-316126-j51dik7f.txt txt: ./txt/cord-316126-j51dik7f.txt summary: title: SARS-CoV-2 and Health Care Worker Protection in Low-Risk Settings: a Review of Modes of Transmission and a Novel Airborne Model Involving Inhalable Particles Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2''s mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. This review attempts to summarize current cumulative data on SARS-CoV-2''s modes of transmission and identify gaps in research while offering preliminary answers to the question on everyone''s mind: is the airborne route significant and should we modify our COVID-19 PPE recommendations for frontline workers in low-risk settings? Given that substantial disagreement persists on the importance of natural aerosol generation by COVID-19 patients, and consequently, the necessary level of respiratory protection in non-AGP contexts, our review will focus on transmission and PPE in low-risk health care settings. abstract: Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2’s mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. The objective of this review is to identify and appraise the available evidence (clinical trials and laboratory studies on masks and respirators, epidemiological studies, and air sampling studies), clarify key concepts and necessary conditions for airborne transmission, and shed light on knowledge gaps in the field. We find that, except for aerosol-generating procedures, the overall data in support of airborne transmission—taken in its traditional definition (long-distance and respirable aerosols)—are weak, based predominantly on indirect and experimental rather than clinical or epidemiological evidence. Consequently, we propose a revised and broader definition of “airborne,” going beyond the current droplet and aerosol dichotomy and involving short-range inhalable particles, supported by data targeting the nose as the main viral receptor site. This new model better explains clinical observations, especially in the context of close and prolonged contacts between health care workers and patients, and reconciles seemingly contradictory data in the SARS-CoV-2 literature. The model also carries important implications for personal protective equipment and environmental controls, such as ventilation, in health care settings. However, further studies, especially clinical trials, are needed to complete the picture. url: https://doi.org/10.1128/cmr.00184-20 doi: 10.1128/cmr.00184-20 id: cord-343528-5283jsnu author: Zhang, Zhao title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission date: 2016-05-04 words: 4745.0 sentences: 251.0 pages: flesch: 55.0 cache: ./cache/cord-343528-5283jsnu.txt txt: ./txt/cord-343528-5283jsnu.txt summary: Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV''s evolutionary history and the positive selection sites in MERS-CoV''s S protein might enable it to infect human. In order to study the temporal and spatial pattern of MERS-CoV transmission, a maximum clade credibility (MCC) tree was constructed using MERS-CoV whole genome sequences without recombinant strains (Fig. 3c) . The amino acid sites under positive selection in MERS-CoV S protein, especially those in its receptor binding domain, might have facilitated its cross-species transmission from animal host to human. All authors reviewed the manuscript. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human. url: https://doi.org/10.1038/srep25049 doi: 10.1038/srep25049 id: cord-347767-aq9niccc author: Zhao, Jie title: Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a date: 2020-06-19 words: 3538.0 sentences: 198.0 pages: flesch: 49.0 cache: ./cache/cord-347767-aq9niccc.txt txt: ./txt/cord-347767-aq9niccc.txt summary: The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. To characterize the effect of herbal medicine, immune function, and inflammatory agents, levels of white blood cells were detected for all patients according to the manufacturer''s instructions at the beginning and at the end of the two weeks. In conclusion, our study suggests that the 5th edition recommendation''s CM prescription, can be safely used in the treatment of severe pneumonia of SARS-COV-2 with yidu-toxicity blocking lung syndrome. abstract: The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-α, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-α (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100%. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings. url: https://www.sciencedirect.com/science/article/pii/S0753332220306296?v=s5 doi: 10.1016/j.biopha.2020.110436 id: cord-321358-plxz5mkg author: Zheng, Jun title: SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat date: 2020-03-15 words: 4759.0 sentences: 251.0 pages: flesch: 53.0 cache: ./cache/cord-321358-plxz5mkg.txt txt: ./txt/cord-321358-plxz5mkg.txt summary: An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. CoVs have been identified in both avian hosts and various mammals, including bat, camels, dogs and masked palm civets, and are previously regarded as pathogens that only cause mild diseases in the immunocompetent people until the emergence of the coronavirus causing severe acute respiratory syndrome (SARS-CoV) in late of 2002 [3] [4] [5] [6] . abstract: An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized. url: https://www.ncbi.nlm.nih.gov/pubmed/32226285/ doi: 10.7150/ijbs.45053 id: cord-290904-ngvhk0qy author: Zheng, Zhiqiang title: Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2 date: 2020-07-16 words: 4471.0 sentences: 246.0 pages: flesch: 57.0 cache: ./cache/cord-290904-ngvhk0qy.txt txt: ./txt/cord-290904-ngvhk0qy.txt summary: In this study, we aim to verify if the sequence of the immunogen used to generate mAb 1A9, as well as three other mAbs, is conserved in different coronaviruses and if these mAbs bind to the S protein of SARS-CoV-2 expressed in mammalian cell lines. IF analysis performed on transiently transfected COS-7 cells showed binding of the four mAbs to this S protein fragment of SARS-CoV-2 ( Figure 2B ). Utility of monoclonal antibody 1A9 for detection of S protein in a sandwich ELISA format and in SARS-CoV-2 infected cells Based on indirect ELISA data, mAb 1A9 has the strongest binding to S protein when compared with the other three mAbs. Hence, a sandwich ELISA was performed to determine if it can be paired with the human mAb CR3022 which is known to bind to the S1 subunit of SARS-CoV-2. abstract: BACKGROUND: A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2. AIM: The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed. METHODS: The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein. RESULTS: An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format. CONCLUSION: The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32700671/ doi: 10.2807/1560-7917.es.2020.25.28.2000291 id: cord-214854-ck61ja2t author: Zhong, Jing title: Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles date: 2020-10-08 words: 2059.0 sentences: 120.0 pages: flesch: 47.0 cache: ./cache/cord-214854-ck61ja2t.txt txt: ./txt/cord-214854-ck61ja2t.txt summary: Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and sensitive detection of specific biomolecules, e.g. protein, DNA/RNA and virus. demonstrated the feasibility of wash-free, sensitive and specific assays for the detection of different viruses, e.g. orchid and influenza viruses, with antibody-functionalized MNPs by measuring the reduction in the ac susceptibility in mixed-frequency ac magnetic fields [23] [24] [25] . All these approaches have demonstrated that MNP-based homogeneous biosensing is a wash-free and mix-and-measure approach for rapid and sensitive detection of specific biomolecules. abstract: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global medical systems and economies, and rules our daily living life. Controlling the outbreak of SARS-CoV-2 has become one of the most important and urgent strategies throughout the whole world. As of October, 2020, there have not yet been any medicines or therapies to be effective against SARS-CoV-2. Thus, rapid and sensitive diagnostics is the most important measures to control the outbreak of SARS-CoV-2. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. Experimental results demonstrate that the proposed approach allows the rapid detection of mimic SARS-CoV-2 with a limit of detection of 0.084 nM (5.9 fmole). The proposed approach has great potential for designing a low-cost and point-of-care device for rapid and sensitive diagnostics of SARS-CoV-2. url: https://arxiv.org/pdf/2010.03886v1.pdf doi: nan id: cord-294363-bv6xa8v8 author: Zhou, Hong title: Potential Therapeutic Targets and Promising Drugs for Combating SARS‐CoV‐2 date: 2020-05-05 words: 8902.0 sentences: 456.0 pages: flesch: 46.0 cache: ./cache/cord-294363-bv6xa8v8.txt txt: ./txt/cord-294363-bv6xa8v8.txt summary: Several studies demonstrated angiotensin converting enzyme 2 (ACE2) as an important therapeutic target of SARS-CoV-2 entry and infection, and many potential targets were subsequently proposed, such as the spike (S) protein and transmembrane serine protease 2 (TMPRSS2). Therefore, accelerating research for potential therapeutic target confirmation, promising drug discovery, and clinical verification development will speed up efforts to combat SARS-CoV-2. In addition to inhibiting the virus directly, ASOs are also expected to target the disease-related proteins involved in the inflammatory cytokine storm process, which could be considered a promising therapeutic strategy for combating SARS-CoV-2 . Although many strategies have been used to block the attachment, entry, replication and release processes to inhibit SARS-CoV-2 infection, how to prevent viral evasion from host immune responses and virus-induced cytopathic effects is considered one of the most urgent problems that need to be solved in SARS-CoV-2-induced pneumonia-associated respiratory syndrome (PARS) patients. abstract: As of April 9, 2020, a novel coronavirus (SARS‐CoV‐2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we have learned the genome structure, epidemiological and clinical characteristics and pathogenic mechanisms of SARS‐CoV‐2. Based on these discoveries, identifying potential targets involved in the processes of virus pathogenesis is urgently needed, and discovering or developing promising drugs based on potential targets is the most pressing need. Therefore, we summarize the potential therapeutic targets involved in virus pathogenesis and discuss the advancements, possibilities and significance of promising drugs based on these targets for treating SARS‐CoV‐2. This review will facilitate the identification of potential targets and provide promising clues for drug development that can be translated into clinical applications for combating SARS‐CoV‐2. url: https://www.ncbi.nlm.nih.gov/pubmed/32368792/ doi: 10.1111/bph.15092 id: cord-302584-fwdpzv85 author: Zhu, Ying title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates date: 2005-01-01 words: 3429.0 sentences: 170.0 pages: flesch: 54.0 cache: ./cache/cord-302584-fwdpzv85.txt txt: ./txt/cord-302584-fwdpzv85.txt summary: title: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates Despite the fact that the SARS-CoV can cause an atypical and fatal form of pneumonia, the genome structure, gene expression pattern, and protein profiles of the virus are similar to those of other conventional coronaviruses [17] , which are only responsible for mild respiratory tract infections in a wide range of animals including humans, pigs, cows, mice, cats, and birds [10, 19] . In this report, we described the isolation of a new SARS-CoV strain (WHU) from a patient in Hubei Province, China during the late period of SARS outbreak. Comparative study of genetic characterization and nucleotide variation of all known SARS-CoV offers insights into understanding functions of the viral genes and revealing the evolution trends of the virus. abstract: Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic. url: https://www.ncbi.nlm.nih.gov/pubmed/15744567/ doi: 10.1007/s11262-004-4586-9 id: cord-268561-vq1uhj5i author: da Silva, Severino Jefferson Ribeiro title: Clinical and Laboratory Diagnosis of SARS-CoV-2, the Virus Causing COVID-19 date: 2020-08-04 words: 9916.0 sentences: 594.0 pages: flesch: 47.0 cache: ./cache/cord-268561-vq1uhj5i.txt txt: ./txt/cord-268561-vq1uhj5i.txt summary: 11 The causative agent was identified as a novel CoV, eventually named SARS-CoV-2, and the respiratory syndrome associated with the infection was designated as coronavirus disease-2019 (COVID-19) by the World Health Organization (WHO). In direct tests, the clinical sample is examined directly for the presence of particles, virus antigens, or viral nucleic acids, whereas indirect methods detect the serological response against the infection (Figure 2 ). 11 Culture-based methods for SARS-CoV-2 detection have been used in research and public health laboratories in different parts of the world, but virus isolation is not recommended as a routine diagnostic procedure because it has low sensitivity, it is time-consuming, and it requires BSL-3 containment. 11 In addition to unequivocally confirming the diagnosis of a SARS-CoV-2 infection, regular sequencing of a percentage of patient samples from clinical cases can be used to monitor changes in the viral genome over time and trace transmission patterns. abstract: [Image: see text] In December 2019, a novel beta (β) coronavirus eventually named SARS-CoV-2 emerged in Wuhan, Hubei province, China, causing an outbreak of severe and even fatal pneumonia in humans. The virus has spread very rapidly to many countries across the world, resulting in the World Health Organization (WHO) to declare a pandemic on March 11, 2020. Clinically, the diagnosis of this unprecedented illness, called coronavirus disease-2019 (COVID-19), becomes difficult because it shares many symptoms with other respiratory pathogens, including influenza and parainfluenza viruses. Therefore, laboratory diagnosis is crucial for the clinical management of patients and the implementation of disease control strategies to contain SARS-CoV-2 at clinical and population level. Here, we summarize the main clinical and imaging findings of COVID-19 patients and discuss the advances, features, advantages, and limitations of different laboratory methods used for SARS-CoV-2 diagnosis. url: https://doi.org/10.1021/acsinfecdis.0c00274 doi: 10.1021/acsinfecdis.0c00274 id: cord-260729-b12v3c8c author: de Lang, Anna title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date: 2007-08-10 words: 6800.0 sentences: 335.0 pages: flesch: 51.0 cache: ./cache/cord-260729-b12v3c8c.txt txt: ./txt/cord-260729-b12v3c8c.txt summary: As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. In order to elucidate early host responses during the acute phase of SARS-CoV infection, we infected cynomolgus macaques with SARS-CoV and used macaque-specific microarrays and real-time (RT)-PCR techniques to study host gene expression profiles. In this study, we simultaneously examined virus replication and host-response gene expression profiles in macaque lungs during the acute phase of SARS to gain more insight into the early events that take place after SARS-CoV infection. In order to visualize the host response in the lungs of SARS-CoV-infected macaques, IFN-b production and translocation of phosphorylated STAT1 was studied using immunohistochemistry. The expression of IFN-b, which strongly correlated to the amount of virus present, continued throughout day 4 and was confirmed using immunohistochemistry; IFN-b-positive cells could be detected in the lungs of the SARS-CoV-infected macaques. abstract: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/17696609/ doi: 10.1371/journal.ppat.0030112 id: cord-332992-8rmqg4rf author: de Vries, A. A. F. title: SARS-CoV-2/COVID-19: a primer for cardiologists date: 2020-07-15 words: 9182.0 sentences: 433.0 pages: flesch: 39.0 cache: ./cache/cord-332992-8rmqg4rf.txt txt: ./txt/cord-332992-8rmqg4rf.txt summary: Although SARS-CoV-2 particles/components have been detected in, for example, endothelial cells, the digestive tract and the liver, not all extrarespiratory manifestations of COVID-19 are necessarily caused by direct viral injury but may also be the consequence of the hypoxaemia, (hyper)inflammatory response, neuroendocrine imbalance and other pathophysiological changes induced by the airway infection [43] . Factors that may contribute to the thrombophilia observed in severely ill COVID-19 patients include the following: (1) a disturbed balance between pro-and anticoagulant activities due to excessive production of proinflammatory cytokines, activation of complement, formation of neutrophil extracellular traps and activation of platelets; (2) inflammation-related endothelial activation; (3) death of SARS-CoV-2-infected endothelial cells; (4) endothelial dysfunction caused by unbalanced angiotensin IIangiotensin II type-1 receptor signalling; (5) formation of prothrombotic antiphospholipid antibodies; (6) immobility-associated reduction of blood flow; (7) hypoxia due to respiratory impairment resulting from SARS-CoV-2-induced lung injury [79] [80] [81] . abstract: In the late autumn of 2019, a new potentially lethal human coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The pandemic spread of this zoonotic virus has created a global health emergency and an unprecedented socioeconomic crisis. The severity of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV‑2, is highly variable. Most patients (~85%) develop no or mild symptoms, while others become seriously ill, some succumbing to disease-related complications. In this review, the SARS-CoV‑2 life cycle, its transmission and the clinical and immunological features of COVID-19 are described. In addition, an overview is presented of the virological assays for detecting ongoing SARS-CoV‑2 infections and the serological tests for SARS-CoV-2-specific antibody detection. Also discussed are the different approaches to developing a COVID-19 vaccine and the perspectives of treating COVID-19 with antiviral drugs, immunomodulatory agents and anticoagulants/antithrombotics. Finally, the cardiovascular manifestations of COVID-19 are briefly touched upon. While there is still much to learn about SARS-CoV‑2, the tremendous recent advances in biomedical technology and knowledge and the huge amount of research into COVID-19 raise the hope that a remedy for this disease will soon be found. COVID-19 will nonetheless have a lasting impact on human society. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12471-020-01475-1) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s12471-020-01475-1 doi: 10.1007/s12471-020-01475-1 id: cord-319877-izn315hb author: de Wit, Emmie title: SARS and MERS: recent insights into emerging coronaviruses date: 2016-06-27 words: 9387.0 sentences: 424.0 pages: flesch: 43.0 cache: ./cache/cord-319877-izn315hb.txt txt: ./txt/cord-319877-izn315hb.txt summary: Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. The downregulation of ACE2 results in the excessive production of angiotensin II by the related enzyme ACE, and it has been suggested that the stimulation of type 1a angiotensin II receptor and Middle East respiratory syndrome coronavirus (MERS-CoV) encode two large polyproteins, pp1a and pp1ab, which are proteolytically cleaved into 16 non-structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have developed mechanisms to interfere with these signalling pathways, as shown; these subversion strategies involve both structural proteins (membrane (M) and nucleocapsid (N)) and non-structural proteins (nsp1, nsp3b, nsp4a, nsp4b, nsp5, nsp6 and papain-like protease (PLpro); indicated in the figure by just their nsp numbers and letters). abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/nrmicro.2016.81 doi: 10.1038/nrmicro.2016.81 id: cord-353293-vjdwh19x author: nan title: Post-COVID-19 global health strategies: the need for an interdisciplinary approach date: 2020-06-11 words: 3856.0 sentences: 175.0 pages: flesch: 36.0 cache: ./cache/cord-353293-vjdwh19x.txt txt: ./txt/cord-353293-vjdwh19x.txt summary: Gemelli IRCSS (Rome, Italy) has set up a multidisciplinary healthcare service called "Post-COVID-19 Day Hospital." The specialist assessments offered to patients are outlined in the following sections. Furthermore, the important role of geriatrician acting as a care manager of patients who suffered COVID-19 disease is described. A respiratory follow-up is of pivotal importance to evaluate lung function, alveolar-arterial gas exchange, and exercise tolerance in recovered non-infective COVID-19 patients [5] . In this Post-COVID-19 Day Hospital, internal medicine and geriatric specialists are integrated with infectious disease physicians, pneumologists, immuno-rheumatologists, and other specialists into the management of the SARS-CoV-2 infection. As a whole, the post-acute care service at the Fondazione Policlinico Gemelli aims at expanding the knowledge of COVID-19 and its impact on health status and care needs as well as at promoting healthcare strategies to treat and prevent the clinical consequence of SARS-CoV-2 infection across different organs and systems. abstract: For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients. url: https://doi.org/10.1007/s40520-020-01616-x doi: 10.1007/s40520-020-01616-x id: cord-310507-5h6egve4 author: van Doorn, Amarylle S. title: Systematic review with meta‐analysis: SARS‐CoV‐2 stool testing and the potential for faecal‐oral transmission date: 2020-08-27 words: 3532.0 sentences: 238.0 pages: flesch: 49.0 cache: ./cache/cord-310507-5h6egve4.txt txt: ./txt/cord-310507-5h6egve4.txt summary: Since December 2019, the world has been dealing with the outbreak of the novel Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) leading to Corona Virus Disease 2019 (COVID-19) that emerged in Wuhan, China. However, there is a growing body of studies in which SARS-CoV-2 RNA was detected in stool samples (including anal swabs) from COVID-19 patients. 11, 15, 16 This study aims to (1) critically assess the clinical relevance of testing stool samples and anal swabs and (2) provide a critical overview of the available literature regarding the faecal-oral transmission of SARS-CoV-2. We collected the following data from the eligible original articles: study design, geographic location, study period, number of patients, age, types of tested specimens, number of tested specimens, methods of the performed tests, duration and prevalence of positive test results in different specimens, disease severity, gastrointestinal symptoms, endoscopic results, specific evidence supporting faecal-oral transmission and remarkable patient/population characteristics. abstract: BACKGROUND: Since the start of the COVID‐19 pandemic, there have been many scientific reports regarding gastrointestinal manifestations. Several reports indicate the possibility of viral shedding via faeces and the possibility of faecal‐oral transmission. AIMS: To critically assess the clinical relevance of testing stool samples and anal swabs and provide an overview of the potential faecal‐oral transmission of SARS‐CoV‐2. METHODS: A systematic literature search with MeSH terms was performed, scrutinising the Embase database, Google scholar, MEDLINE database through PubMed and The Cochrane Library, including articles from December 2019 until July 7 2020. Data were subsequently analysed with descriptive statistics. RESULTS: Ninety‐five studies were included in the qualitative analysis. 934/2149 (43%) patients tested positive for SARS‐CoV‐2 in stool samples or anal swabs, with positive test results up to 70 days after symptom onset. A meta‐analysis executed with studies of at least 10 patients revealed a pooled positive proportion of 51.8% (95% CI 43.8 ‐ 59.7%). Positive faecal samples of 282/443 patients (64%) remained positive for SARS‐CoV‐2 for a mean of 12.5 days, up to 33 days maximum, after respiratory samples became negative for SARS‐CoV‐2. Viable SARS‐CoV‐2 was found in 6/17 (35%) patients in whom this was specifically investigated. CONCLUSIONS: Viral shedding of SARS‐CoV‐2 in stool samples occurs in a substantial portion of patients, making faecal‐oral transmission plausible. Furthermore, detection in stool sample or anal swab can persist long after negative respiratory testing. Therefore, stool sample or anal swab testing should be (re)considered in relation to decisions for isolating or discharging a patient. url: https://doi.org/10.1111/apt.16036 doi: 10.1111/apt.16036 id: cord-328175-4i3cz20j author: van Doremalen, Neeltje title: Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets date: 2017-07-31 words: 5150.0 sentences: 272.0 pages: flesch: 51.0 cache: ./cache/cord-328175-4i3cz20j.txt txt: ./txt/cord-328175-4i3cz20j.txt summary: Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Here we assess the effect of treatment with marmoset-derived hyperimmune plasma as well as the human mAb m336 on disease outcome in the recently developed marmoset MERS-CoV infection model, which recapitulates severe respiratory disease (Falzarano et al., 2014) . Viral loads in lung tissues from hyperimmune plasma-treated compared to control animals were found to be significantly lower using a onetailed unpaired Student''s t-test (average of 4.0 Â 10 4 and 1.2 Â 10 6 TCID 50 equivalent/gram, respectively, p-value ¼ 0.008). In this study, hyperimmune plasma treatment of marmosets inoculated with MERS-CoV resulted in a small (0.5e1 log) but significant reduction in respiratory tract viral loads, as well as reduced disease severity such as observed with radiographs, compared to marmosets treated with non-convalescent plasma or PBS. abstract: Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease. url: https://www.sciencedirect.com/science/article/pii/S0166354216305381 doi: 10.1016/j.antiviral.2017.03.025 id: cord-265329-bsypo08l author: van Dorp, Lucy title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 date: 2020-05-05 words: 4915.0 sentences: 270.0 pages: flesch: 49.0 cache: ./cache/cord-265329-bsypo08l.txt txt: ./txt/cord-265329-bsypo08l.txt summary: Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. The extraordinary availability of genomic data during the COVID-19 pandemic has been made possible thanks to a tremendous effort by hundreds of researchers globally depositing SARS-CoV-2 assemblies (Table S1 ) and the proliferation of close to real time data visualisation and analysis tools including NextStrain (https://nextstrain.org) and CoV-GLUE (http://cov-glue.cvr.gla.ac.uk). In this work we use this data to analyse the genomic diversity that has emerged in the global population of SARS-CoV-2 since the beginning of the COVID-19 pandemic, based on a download of 7710 assemblies. The genomic diversity of the global SARS-CoV-2 population being recapitulated in multiple countries points to extensive worldwide transmission of COVID-19, likely from extremely early on in the pandemic. abstract: SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes. url: https://api.elsevier.com/content/article/pii/S1567134820301829 doi: 10.1016/j.meegid.2020.104351 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel