# ent

id: cord-322166-ajolu2rh
type: PROTEIN
entity:
  receptor binding protein hemagglutinin HA neuraminidase NA nucleoprotein NP non structural protein 1 NS1 nuclear export protein NEP


id: cord-322166-ajolu2rh
type: ORG
entity:
  Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection


id: cord-322166-ajolu2rh
type: CHEMICAL
entity:
  influenza A virus segment 7 spliced mRNAs is regulated by the NS1 protein Pre pandemic and pandemic influenza vaccines


id: cord-312080-pu6m4qad
type: DISEASE
entity:
  infectious human papillomavirus Elucidation of natural virus host interactions Microfluidic fabrication


id: cord-312080-pu6m4qad
type: DISEASE
entity:
  drug discovery and cell based biosensors Replication of human noroviruses in stem cell derived human enteroids Induction of productive human papillomavirus type 11 life cycle


id: cord-003246-3ajfb18m
type: ORG
entity:
  the National Infectious Disease Diagnostic Reagent and Vaccine Engineering Technology Research Center Xiamen University


id: cord-273608-dxx3p1x5
type: DISEASE
entity:
  influenza and respiratory syncytial virus in the United States Respiratory syncytial virus RSV RNA loads in peripheral blood correlates


id: cord-025181-eg108wcd
type: DNA
entity:
  DENV 3 0 UTR Forward 5 0 TGAYAAGCARTCAGACAC 3 0 Reverse 5 0 TCAC CARRCTCCCTTTGC 3 0 Fluorescence probe 5 0 CCA GAGATCCTGCTGTCTC 3 0


id: cord-354529-k8p2u7iq
type: RNA
entity:
  SARS CoV 2 RNA 44 0 30 0 47 0 days still needed to hospitalize and separate which may cause a huge cost during COVID 19 pandemic In fact individual human case studies reported long periods of viral shedding that Recently a report have shown long term coexisting of SARS CoV 2


id: cord-354529-k8p2u7iq
type: EVENT
entity:
  Trial Version of the New Coronavirus Pneumonia Prevention and Control Program Chinese National Health Commission 2020


id: cord-295640-mhfu0e9r
type: CELL_LINE
entity:
  BD Franklin Lakes NJ USA Peptides NP55 69 RLIQNSLTIERMVLS H 2drestricted Th epitope NP147 155 TYQRTRALV H 2drestricted CTL epitope


id: cord-295640-mhfu0e9r
type: DISEASE
entity:
  influenza A virus hemagglutinin neuraminidase and M2e in conferring cross protection Multigenic DNA vaccine induces protective crossreactive T cell responses


id: cord-025232-5itrsfmk
type: PROTEIN
entity:
  major neutralizing epitope epsilon Crawford Miksza and Schnurr 1996 Singh et al 2015 Each hexon monomer


id: cord-025232-5itrsfmk
type: DNA
entity:
  primer pairs Ad3 GZ01 EcoR V HexF 5 0 TGAGATATCGCCACCATGGCCACCCCATC 3 0 and Ad3 GZ01 HexR Xho I 5 0 AGACTCGAGTTATGTGG TGGCGTTGCC 3 0


id: cord-319501-a2x1hvkk
type: PROTEIN
entity:
  downstream effectors tumor necrosis factor receptor associated factor 3 TRAF3 TANK binding kinase 1 TBK1


id: cord-329876-4cgrjnjo
type: PROTEIN
entity:
  pro N 3 fluorophenyl methyl 1 1R 1 naphthalen 1 ylethyl piperidine 4 carboxamide compound 3k IC 50 0 15 0 01 μmol L


id: cord-329876-4cgrjnjo
type: ORG
entity:
  the human respiratory tract Identification of severe acute respiratory syndrome coronavirus replicase


id: cord-329876-4cgrjnjo
type: CHEMICAL
entity:
  N 3 fluorophenyl methyl 1 1R 1 naphthalen 1 ylethyl piperidine 4 carboxamide compound 3k IC 50 0 15 0 01 μmol L


id: cord-274785-9jgg8ukr
type: PROTEIN
entity:
  vaccinia virus ssDNA binding protein I3 Human cytomegalovirus pTRS1 and pIRS1 antagonize protein kinase R


id: cord-014938-7evmiuv5
type: DISEASE
entity:
  coronavirus in pneumocytes of the lung Fuliminant hepatic failure hepatitis virus strain 3 infection


id: cord-273373-5elel6qo
type: PROTEIN
entity:
  RNA dependent RNA polymerase nsp13 5 to 3 RNA helicase NTPase RNA 5 triphosphatase nsp14 3 to 5 exoribonuclease nsp15 uridylate specific endoribonuclease


id: cord-014923-gfiqjgxg
type: PROTEIN
entity:
  SARS Cov S protein residues 262 606 S1 2 encoding 314 606 S1 3 encoding 388 606 S1 4 encoding 314 387 S1 5 encoding 262 496 S1 6 encoding 262 387 S1 7 encoding 388 496 Fig 1


id: cord-014923-gfiqjgxg
type: PROTEIN
entity:
  recombinant protein S1 1 S1 7 M protein marker 1 S1 1 2 S1 2 3 S1 3 4 S1 6 5 S1 5 6 S1 4 7 S1 7 E coli


# bib

id: cord-003246-3ajfb18m
author: Liang, Zhenli
date: 2018-04-19
txt: ./txt/cord-003246-3ajfb18m.txt
cache: ./cache/cord-003246-3ajfb18m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178549/
doi: 10.1007/s12250-018-0029-y
abstract: nan
summary:
  Previous studies have shown that lung injury in patients with HFMD is associated with neurogenic pulmonary edema (NPE) after EV71 infection of the brainstem, rather than with direct viral invasion (Jiang et al. Protein edema in the alveolar space with fibrin exudation was observed inside, and some alveoli were filled with mononuclear cells, alveolar macrophages, exfoliated epithelial cells and cell debris (G); the alveolar septum was widened, the capillaries in the septum were highly dilated and congested, with infiltration of inflammatory cells (H); intrapulmonary bronchitis and bronchiolitis, diffuse or focal infiltration of inflammatory cells in the wall and surrounding tissues (I, J); compensatory emphysema phenomenon of ruptured alveolar wall and fusion of pulmonary alveoli (K); the lymph nodes near the hilar bronchus indicated a reactive hyperplasia, germinal center enlargement, paracortical zone atrophy, and lymphocyte depletion (L) (black arrow). Lung tissues of EV71 infected patients with severe HFMD showed interstitial pneumonia and positive viral antigens in the pulmonary epithelial cells and macrophages.

title:
  Histopathological Features and Viral Antigen Distribution in the Lung of Fatal Patients with Enterovirus 71 Infection


id: cord-005340-o7tkxs3s
title: Import of Rift Valley fever to China: a potential new threat?
author: Fu, Xinliang
date: 2016-10-27
txt: ./txt/cord-005340-o7tkxs3s.txt
cache: ./cache/cord-005340-o7tkxs3s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090825/
doi: 10.1007/s12250-016-3876-4
abstract: [Image: see text]
summary:
  Confronted with this imported case, the government in China has implemented surveillance, monitoring, and other measures to prevent the spread of RVF in China (http://www. Based on the lessons learned during the outbreaks in Saudi Arabia and Yemen, and given these conditions, there is a high risk that the imported case may spread or even cause an outbreak, if proper measures to prevent and control RVF are not implemented. Early detection of suspected cases is the key to ensure that timely control measures are implemented to prevent the spread and outbreak of emerging or re-emerging infectious diseases, such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Ebola, as well as RVF . Meanwhile, the effectiveness of strengthening collaboration and coordination across sectors, such as government, the Centers for Disease Control and Prevention, researchers, and hospitals, to make prevention and control measures more efficient, was demonstrated when the MERS case was imported in China (Su et al., 2015; Su et al., 2016b) and during the RVF outbreak in Saudi Arabia (Himeidan et al., 2014) .


id: cord-005372-7x8ro8p2
author: Jiménez, Luisa Fernanda Mancipe
date: 2014-08-08
txt: ./txt/cord-005372-7x8ro8p2.txt
cache: ./cache/cord-005372-7x8ro8p2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091121/
doi: 10.1007/s12250-014-3471-5
summary:
  PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh. Swine infl uenza is an acute, highly contagious respiratory disease resulting from infection with type A infl uenza virus, a member of the Orthomyxoviridae family. PRDC results from a combination of viral and bacterial agents, including porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and porcine circovirus type 2 (PCV2) (Kim J, et al., 2003) . The main goal of the current research was to generate surveillance, epidemiological, antigenic as well as phylogenetic data to ascertain the presence of swine influenza (H1N1) pandemic virus and determine its association with PRDC (PRRSV, Myh, APP and PCV2) in sows from production farms in Colombia.

title:
  Association of swine influenza H1N1 pandemic virus (SIV-H1N1p) with porcine respiratory disease complex in sows from commercial pig farms in Colombia

abstract:
  Porcine respiratory disease complex (PRDC) is a serious health problem that mainly affects growing and finishing pigs. PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). To characterize the specific role of swine influenza virus in PRDC presentation in Colombia, 11 farms from three major production regions in Colombia were examined in this study. Nasal swabs, bronchial lavage and lung tissue samples were obtained from animals displaying symptoms compatible with SIV. Isolation of SIV was performed in 9-day embryonated chicken eggs or Madin-Darby Canine Kidney (MDCK) cells. Positive isolates, identified via the hemagglutination inhibition test, were further analyzed using PCR. Overall, 7 of the 11 farms were positive for SIV. Notably, sequencing of the gene encoding the hemagglutinin (HA) protein led to grouping of strains into circulating viruses identified during the human outbreak of 2009, classified as pandemic H1N1-2009. Serum samples from 198 gilts and multiparous sows between 2008 and 2009 were obtained to determine antibody presence of APP, Myh, PCV2 and PRRSV in both SIV-H1N1p-negative and -positive farms, but higher levels were recorded for SIV-H1N1p-positive farms. Odds ratio (OR) and P values revealed statistically significant differences (p<0.05) in PRDC presentation in gilts and multiparous sows of farms positive for SIV-H1N1p. Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh.


id: cord-005397-i7x50taa
title: Preparation and identification of anti-rabies virus monoclonal antibodies
author: Wang, Wen-juan
date: 2012-06-09
txt: ./txt/cord-005397-i7x50taa.txt
cache: ./cache/cord-005397-i7x50taa.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091418/
doi: 10.1007/s12250-012-3242-0
summary:
  To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection, anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6–8 week old female BALB/c mice. Spleen cells and SP2/0 myeloma cells were fused according to conventional methods: the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally, systematic identification of subclass, specificity and sensitivity was carried out. Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12, with ascitic fluid titers of 1:8000 and 1:10000, respectively. Thus, the preparation of potent and specific monoclonal antibodies against rabies virus will contribute significantly to development of techniques for laboratory diagnosis of rabies.

abstract:
  To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection, anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6–8 week old female BALB/c mice. Spleen cells and SP2/0 myeloma cells were fused according to conventional methods: the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally, systematic identification of subclass, specificity and sensitivity was carried out. Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12, with ascitic fluid titers of 1:8000 and 1:10000, respectively. Both belonged to the IgG2a subclass. These strains secrete potent, stable and specific anti-rabies virus monoclonal antibodies, which makes them well suited for the development of rabies diagnosis reagents.


id: cord-006752-fmdvwnbw
author: Mao, Huawei
date: 2014-06-17
txt: ./txt/cord-006752-fmdvwnbw.txt
cache: ./cache/cord-006752-fmdvwnbw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102336/
doi: 10.1007/s12250-014-3473-3
summary:
  While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. In the 2009 H1N1 pandemic (pdmH1N1) outbreak, we analyzed the conserved CD8 T cell epitopes in pdmH1N1 virus, and demonstrated that the conserved epitope-specifi c T cells established by seasonal infl uenza virus could cross react against the pandemic virus, which might contribute to the milder pandemic H1N1 illness overall and the lower infection attack rate in young adults even though they did not have detectable cross-neutralizing antibody (Tu W, et al., 2010) . Like avian H5N1 infection, most of patients with H7N9 infection who were hospitalized for medical care had severe illness, although both of the two viruses had conserved T cell epitopes that are shared with seasonal infl uenza virus.

title:
  Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus

abstract:
  A novel avian influenza A (H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses (compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.


id: cord-014920-mmykzj9w
author: Wang, Shi-qun
date: 2008-05-10
txt: ./txt/cord-014920-mmykzj9w.txt
cache: ./cache/cord-014920-mmykzj9w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090866/
doi: 10.1007/s12250-008-2952-9
summary:
  The X protein (HBx) of Human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes, as well as playing a critical role in pathogenesis and the development of Hepatocellular carcinoma (HCC). In addition, the viral X region appears to have pleiotropic effects that could also be involved in the oncogenic processes, including transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA (8, 14, 16) . Many human hepatocellular carcinomas contain integrated HBV, and the viral X protein appears to have pleiotropic effects that could be involved in the oncogenic process. Putative tumor suppressor YueF affects the functions of hepatitis B virus X protein in hepatoma cell apoptosis and p53 expression The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression

title:
  Biological effects of HBV X protein on hepatocellular carcinogenesis in association with cellular factors

abstract:
  The X protein (HBx) of Human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes, as well as playing a critical role in pathogenesis and the development of Hepatocellular carcinoma (HCC). Here we described the biological effects of HBx in association with four cellular factors, including inflammatory factors (COX-2 and iNOS), oncoprotein (Ras), and a newly identified tumor suppressor (YueF). The characteristics of these effectors, which might be associated with hepatocellular carcinoma, are also discussed.


id: cord-014923-gfiqjgxg
title: The functional motif of SARS-CoV S protein involved in the interaction with ACE2
author: Zhang, Yi
date: 2009-09-16
txt: ./txt/cord-014923-gfiqjgxg.txt
cache: ./cache/cord-014923-gfiqjgxg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090955/
doi: 10.1007/s12250-007-0054-8
summary:
  It has been established that the S protein in this pathogen plays an important rule in the adsorption and penetration of SARS-CoV into the host cell by interaction with the ACE2 receptor. To determinant which functional motif of the S protein was involved in the interaction with ACE2, seven truncated S proteins deleted from the N or C terminal were obtained by an E.coli expression system and purified by column chromatography to homogeneity. The adsorption were quantified by ELISA, and the results indicated that amino acids from 388 to 496 of the S protein was responsible for the interaction with the ACE2 receptor, and the interaction could be completely disrupted by an antibody specific to these amino acids. Our results showed that S1-1, S1-2, S1-3, S1-5 and S1-7 can interact with purified ACE2 protein specifically, but S1-4 and S1-6 cannot interact with this receptor. Inactivated SARS-CoV vaccine elicits high titers of spike protein specific antibodies that block receptor binding and virus entry

abstract:
  SARS-CoV is a newly discovery pathogen causing severe acute respiratory problems. It has been established that the S protein in this pathogen plays an important rule in the adsorption and penetration of SARS-CoV into the host cell by interaction with the ACE2 receptor. To determinant which functional motif of the S protein was involved in the interaction with ACE2, seven truncated S proteins deleted from the N or C terminal were obtained by an E.coli expression system and purified by column chromatography to homogeneity. Each truncated S protein was fixed on to the well of an ELISA plate and an interaction was initiated with the ACE2 protein. The adsorption were quantified by ELISA, and the results indicated that amino acids from 388 to 496 of the S protein was responsible for the interaction with the ACE2 receptor, and the interaction could be completely disrupted by an antibody specific to these amino acids. Deletions adjacent to this domain did not appear to have a significant impact on the interaction with ACE2, suggesting that the S protein of SARS-CoV could be developed as a vaccine to prevent the spread of SARS-CoV.


id: cord-014927-g4r7j8hk
title: AIDS research and its role in China’s AIDS prevention and control policies
author: Shao, Yi-ming
date: 2008-01-13
txt: ./txt/cord-014927-g4r7j8hk.txt
cache: ./cache/cord-014927-g4r7j8hk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091035/
doi: 10.1007/s12250-007-0042-z
summary:
  Since then, the government has been increasing investment in science and technology with major emphasis on both infectious diseases control and new drug research and development. For the first time, development of 100 new drugs and control of major infectious diseases (AIDS, HBV, TB and other emerging infectious diseases) have been selected as national key scientific projects. The epidemic in China began at the end of the 1980s, when IDUs in Ruili, a small town bordering Myanmar in Yunnan province, were found to be infected by HIV. By the mid 1990s, the HIV/AIDS epidemic was scaled-up by both further spread of drug abuse in other regions and blood contamination in the illegal plasma collection activities in central China (13, 14) . HIV infected people were first identified in Intravenous drug users in China Control of transmission of HIV among drug users and commercial blood donors

abstract:
  By the end of 2005, the estimated number of HIV infected people in China was 650,000. The seriousness of the epidemic calls for effective control measures to tackle the problems in order to avoid the tragedy in Africa from happening in China. “Prevention First” is the cornerstone of the country’s health policy. On 2003 World AIDS Day, Premier Jiabao Wen announced a new national AIDS control policy, “Four Frees and One Care”. This policy clearly shows that the Chinese government has once again taken full responsibility to solve public health problems and has profound impact far beyond the AIDS field. In early 2006, the central government put scientific and technology innovation as a national priority and set the target to build an innovative China by year 2020. Since then, the government has been increasing investment in science and technology with major emphasis on both infectious diseases control and new drug research and development. For the first time, development of 100 new drugs and control of major infectious diseases (AIDS, HBV, TB and other emerging infectious diseases) have been selected as national key scientific projects. China’s best minds in related fields will be pooled to work together in order to remove the technical barriers blocking efficient control of the major infectious disease in China. Knowledge on molecular epidemiology, immunology, pathogenesis, HAART, as well as HIVDR strains will certainly provide urgently needed scientific information for China’s AIDS control program. Only evidence-based strategy from good research will provide long-term effective control of AIDS.


id: cord-014932-web2tdef
title: Cloning the structure genes and expression the N gene of porcine epidemic diarrhea virus DX
author: Li, Jian-qiang
date: 2009-05-28
txt: ./txt/cord-014932-web2tdef.txt
cache: ./cache/cord-014932-web2tdef.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091100/
doi: 10.1007/s12250-009-2982-y
summary:
  The structure genes spike (S), nucleocapsid (N), membrane (M), small membrane (sM) of a porcine epidemic diarrhea virus (PEDV) strain DX isolated in Gansu province, North-west of China, were cloned, sequenced and compared with published sequences of PEDV strains. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03 Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03 Cloning and sequence analysis of the Korean strain of spike gene of Porcine epidemic diarrhea virus and expression of its neutralizing epitope in plants Cloning and Sequence Analysis of the Nucleocapsid Gene of Porcine Epidemic Diarrhea Virus Chinju99 Cloning and sequence analysis of the spike gene of Porcine epidemic diarrhea virus Chiju99

abstract:
  The structure genes spike (S), nucleocapsid (N), membrane (M), small membrane (sM) of a porcine epidemic diarrhea virus (PEDV) strain DX isolated in Gansu province, North-west of China, were cloned, sequenced and compared with published sequences of PEDV strains. The nucleotide sequences encoding the entire S, sM, M and N genes open reading frame (ORF) of DX were 4 152, 231, 681 and 1 326 bases long respectively. There were transcription regulatory sequences (TRSs) upstream of the initiator ATG of the S, N and M genes. The amino acids sequences of S, M and N contained 30, 3 and 7 potential asparagine (N)-linked glycosylation sites. Homologous analysis and phylogenetic trees showed that DX had the closest relationship with strains LJB/06, JS-2004-2Z and CH/HLJH/06 that were also isolated from China and indicated the prevalence of some PEDV isolates in China were widespread since the JS-2004-2Z strain originated from the south of the China, and LJB/06 and CH/HLJH/06 were isolated from northeast China. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. The recombinant plasmid was then transformed into E.coli Rossta. SDS-PAGE showed there was a protein of about 55kDa as expected and Western blot indicated the N protein had biological activity.


id: cord-014938-7evmiuv5
author: Wei-ming, Yan
date: 2008-01-13
txt: ./txt/cord-014938-7evmiuv5.txt
cache: ./cache/cord-014938-7evmiuv5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091223/
doi: 10.1007/s12250-007-0020-5
summary:
  title: Expression of prothrombinase/fibroleukin gene fg12 in lung impairment in a murine severe acute respiratory syndrome model To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. In a separate experiment, tissues including lungs, spleen, liver, kidneys, intestine, heart, brain were collected at a series of time points from Balb/cJ mice infected with MHV-3 through trachea. Detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung The clinical pathology of severe acute respiratory syndrome (SARS): a report from China Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore Discovery of novel human and animal cells infected by the severe acute respiratory syndrome coronavirus by replication-specific multiplex reverse transcription-PCR A novel coronavirus associated with severe acute respiratory syndrome

title:
  Expression of prothrombinase/fibroleukin gene fg12 in lung impairment in a murine severe acute respiratory syndrome model

abstract:
  To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.


id: cord-014946-l3vwb2v7
title: Genetic variation analyses of nsp2 gene of PRRSV in Ningxia Hui Autonomous Region of China
author: Tian, Hong
date: 2009-05-28
txt: ./txt/cord-014946-l3vwb2v7.txt
cache: ./cache/cord-014946-l3vwb2v7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091468/
doi: 10.1007/s12250-009-3017-4
summary:
  title: Genetic variation analyses of nsp2 gene of PRRSV in Ningxia Hui Autonomous Region of China To gain a better understanding of the genetic diversity and evolution of PRRSV in the Ningxia Hui Nationality Autonomous Region (Ningxia) of China, the nsp2 genes from a series of PRRSV strains collected from the region in 2007 were partially sequenced. Comparison of the nucleotide sequence with ch-1a indicated that nsp2 genes of seventeen Ningxia isolates (NX strain) have deletions of 87 nucleotides. The nsp2 genes of the seventeen isolates had 74.9%–100% nucleotide sequence identities with each other. The amplified PCR products were analyzed by agarose gel electrophoresis and purified using the QIAquick gel extraction kit (Qiagen) per the manufacturer''s protocol. All nucleotide sequences were obtained from clinical sample RNA by direct sequencing of PCR products. The nsp2 genes of seventeen isolates had 74.9%-100% nucleotide sequence identity with each other (Fig.3) .

abstract:
  To gain a better understanding of the genetic diversity and evolution of PRRSV in the Ningxia Hui Nationality Autonomous Region (Ningxia) of China, the nsp2 genes from a series of PRRSV strains collected from the region in 2007 were partially sequenced. These sequences were then analyzed along with the classical strain (ch-1a) and two other epidemic strains SD (3) and SD2006. Comparison of the nucleotide sequence with ch-1a indicated that nsp2 genes of seventeen Ningxia isolates (NX strain) have deletions of 87 nucleotides. Sequence analysis indicated that homology between the Ningxia strain and ch-1a was 60.3%–79.9% in the nucleotide sequence, and homology between the NX strains and SD strains was 80.3%–98.8% in the nucleotide sequence. The nsp2 genes of the seventeen isolates had 74.9%–100% nucleotide sequence identities with each other. This study was undertaken to assess the regional variation of prevalent PRRSV and to establish a sequence database for PRRSV molecular epidemiological studies.


id: cord-025181-eg108wcd
author: Zheng, Zhihang
date: 2020-05-25
txt: ./txt/cord-025181-eg108wcd.txt
cache: ./cache/cord-025181-eg108wcd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246292/
doi: 10.1007/s12250-020-00229-y
summary:
  In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. Further, we compared the infectivity of these two viral variants in a self-limited infection model, in which type I IFN receptor of wild-type Balb/c mice had been transiently blocked before infection, and found only the virus strain exhibiting larger plaque size caused infectious viral particles in sera. We have recently developed a ZIKV infection model in Balb/c mice with transient blockage of type I IFN Fig. 2 Phylogenetic analysis of DENV-2 1D4-5-SP and DENV-2 8H2-7-LP with representative serotype-2 dengue viruses of different genotypes isolated from different geographical regions.

title:
  Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate

abstract:
  Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome in patients. Each year, 390 million people are estimated to be infected by four serotypes of dengue virus, creating a great burden on global public health and local economy. So far, no antiviral drug is available for dengue disease, and the newly licensed vaccine is far from satisfactory. One large obstacle for dengue vaccine and drug development is the lack of suitable small animal models. Although some DENV infection models have been developed, only a small number of viral strains can infect immunodeficient mice. In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. This study not only offers new small animal models of dengue viral infection, but also provides new viral variants for further investigations on dengue viral pathogenesis.


id: cord-025232-5itrsfmk
author: Yan, Yuqian
date: 2020-05-26
txt: ./txt/cord-025232-5itrsfmk.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248191/
doi: 10.1007/s12250-020-00234-1
summary:
  The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases. In this study, the commercially-available and gene therapy use approved replication-defective HAdV-5 vector was used to construct a recombinant attenuated human adenovirus type 3 vaccine (Ginn et al. The complete hexon gene of HAdV-3 GZ01 was cloned into the AdEasy TM Adenoviral Vector, and this type-specific antigen was expressed when the recombinant adenovirus vaccine was inoculated into mice. The recombinant vaccine is expected to be used in the prevention of ARD outbreaks caused by HAdV-3 infections, and to serve as a model using adenovirus vectors for the construction of other vaccines against additional important serotypes of adenoviral respiratory pathogens. Mice were either inoculated with HAdV-3 wild-type strain GZ01 or immunized with the rAd3H recombinant vaccine by either the intranasal route or intramuscular route, respectively, to assess the antibody titer.

title:
  Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: “Adenovirus Vaccine Within an Adenovirus Vector”

abstract:
  Human adenoviruses (HAdVs) are highly contagious and result in large number of acute respiratory disease (ARD) cases with severe morbidity and mortality. Human adenovirus type 3 (HAdV-3) is the most common type that causes ARD outbreaks in Asia, Europe, and the Americas. However, there is currently no vaccine approved for its general use. The hexon protein contains the main neutralizing epitopes, provoking strong and lasting immunogenicity. In this study, a novel recombinant and attenuated adenovirus vaccine candidate against HAdV-3 was constructed based on a commercially-available replication-defective HAdV-5 gene therapy and vaccine vector. The entire HAdV-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system. The resultant recombinants expressing the HAdV-3 hexon protein were rescued in AD293 cells, identified and characterized by RT-PCR, Western blots, indirect immunofluorescence, and electron microscopy. This potential vaccine candidate had a similar replicative efficacy as the wild-type HAdV-3 strain. However, and importantly, the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twenty-generation passages in AD293 cells. This represents a significant safety feature. The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAdV-3. Therefore, this recombinant, attenuated, and safe adenovirus vaccine is a promising HAdV-3 vaccine candidate. The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.


id: cord-033952-b9fxqnni
title: Hantavirus Infection during Pregnancy
author: Lu, Deng-Hui
date: 2020-10-19
txt: ./txt/cord-033952-b9fxqnni.txt
cache: ./cache/cord-033952-b9fxqnni.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571305/
doi: 10.1007/s12250-020-00300-8
summary:
  Hantaviruses cause two clinical syndromes in humans; designated hemorrhagic fever with renal syndrome (HFRS), and hantavirus cardiopulmonary syndrome (HPS). However, the cases of women infected with hantavirus during pregnancy are rarely reported even in areas where hantaviruses are concentrated, which poses certain difficulties for subsequent research and clinical management. (1999) reviewed five cases of HPS during pregnancy, and as expected, there was no evidence of vertical transmission, though SNV infections mostly had severe consequences, even death, in pregnant women and fetuses. Although there are not many cases of hantavirus infection reported in pregnant women, even in the endemic areas, clinicians are expected to thoroughly consider severe consequences when they receive patients with similar symptoms. Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four pregnant Chinese women Clinical analysis of 21 cases of hemorrhagic fever with pregnancy renal syndrome Clinical analysis of 21 cases of hemorrhagic fever with pregnancy renal syndrome

abstract:
  Hantavirus infection is a global health challenge, causing widespread public concern. In recent years, cases of hantavirus infection in pregnant women have been reported in many countries. The infected pregnant women and their fetuses appear to have more severe clinical symptoms and worse clinical outcomes. Hence, to study the prevalence of hantavirus infection in pregnant women, this study will focus on the epidemiological distribution of the virus, different virus species penetrating the placental barrier, and factors affecting the incidence and clinical outcome of the infection in pregnant women and their fetuses. In addition, this review will also discuss the diagnostic tools and treatments for pregnant patients and provide an overview of the relevant future research.


id: cord-259443-5sv3dwbs
author: Banik, Gouri Rani
date: 2016-01-25
txt: ./txt/cord-259443-5sv3dwbs.txt
cache: ./cache/cord-259443-5sv3dwbs.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-015-3679-z
doi: 10.1007/s12250-015-3679-z
abstract: [Image: see text]
summary:
  title: Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia Initially, only limited information such as patients'' age, sex, nationality, address, date of diagnosis, presenting symptoms, and presence of any pre-existing condition were made publicly available; however, since 24 th September 2014, additional information on likely exposure to animals and other suspected MERS cases were added, and it was recorded whether the exposure likely occurred at health care settings or in community settings. In our study, presence of a respiratory disease was not a significant risk factor and we did not explore the association of older age with mortality, because essentially all patients aged ≥ 65 years in our cohort had a pre-existing disease, but age itself could be an independent risk factor, as other studies from Saudi Arabia and South Korea demonstrated that age > 60 years (in some studies ≥ 65 years) was significantly associated with mortality (Feikin et al., 2015; Majumder et al., 2015; Saad et al., 2014) .

title:
  Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia


id: cord-261415-qxl14j2m
author: Fu, Yajing
date: 2020-03-03
txt: ./txt/cord-261415-qxl14j2m.txt
cache: ./cache/cord-261415-qxl14j2m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32125642/
doi: 10.1007/s12250-020-00207-4
summary:
  In addition, given that uncontrolled pulmonary inflammation is likely a leading cause of fatality in SARS-CoV-2 infection, we also attempt to speculate possible therapeutic interventions that may be applied to attenuate inflammatory responses in order to reduce mortality (Fig. 2) . In SARS-CoV infection, viroporin 3a has also been shown to trigger the activation of NLRP3 (NOD-like receptor protein 3) inflammasome and the secretion of IL-1b in bone marrowderived macrophages, suggesting the induction of cell pyroptosis , which can cause the release of large amounts of proinflammatory factors (Fink and Cookson 2005) . However, previous studies in animal models have shown that in SARS-CoV infection, such anti-S protein-neutralizing antibodies (anti-S-IgG) can also cause severe lung injury by altering inflammatory responses (Liu et al. This animal study suggests that despite viral suppression, the presence of anti-spike protein antibody at the acute stage of SARS-CoV infection can actually cause severe acute lung injury that persists until the late stages.

title:
  Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools

abstract:
  Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.


id: cord-269021-juh2qkm0
title: The Rapid Assessment and Early Warning Models for COVID-19
author: Bai, Zhihua
date: 2020-04-01
txt: ./txt/cord-269021-juh2qkm0.txt
cache: ./cache/cord-269021-juh2qkm0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00219-0
doi: 10.1007/s12250-020-00219-0
summary:
  Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. In the case of a gradually improved infectious disease surveillance system, the research on forecasting and early warning of epidemics based on models has become the focus of the public health system. In response to the current epidemic of SARS-CoV-2, many researchers have developed mathematical models with varying degrees of complexity, aiming to assess the capacity of pathogen transmission and which interventions are most likely to be effective (Fig. 2) . Estimating the unreported number of novel coronavirus (2019-nCoV) cases in China in the first half of January 2020: a data-driven Modelling analysis of the early outbreak

abstract:
  Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. Rapid assessment and early warning are essential for outbreak analysis in response to serious public health events. This paper reviews the current model analysis methods and conclusions from both micro and macro perspectives. The establishment of a comprehensive assessment model, and the use of model analysis prediction, is very efficient for the early warning of infectious diseases. This would significantly improve global surveillance capacity, particularly in developing regions, and improve basic training in infectious diseases and molecular epidemiology.


id: cord-273373-5elel6qo
title: Recent progress in the discovery of inhibitors targeting coronavirus proteases
author: Wang, Haofeng
date: 2016-02-19
txt: ./txt/cord-273373-5elel6qo.txt
cache: ./cache/cord-273373-5elel6qo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26920707/
doi: 10.1007/s12250-015-3711-3
summary:
  The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. Structural analyses revealed that the substrate-binding pockets of various CoV M pro s are highly conserved, which led to the concept of "widespectrum inhibitors" for targeting all CoVs. Through a structure-based drug design, we have identified a lead compound named N3 with potent inhibitory activity against all M pro s tested ( Figure 2D) . Structurebased design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): expression, purification, characterization, and inhibition

abstract:
  Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. The fatal outbreak of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) highlights the threat posed by this unique virus subfamily. However, no specific drugs have been approved to treat CoV-associated diseases to date. The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. This review summarizes the recent advances in biological and structural studies, together with the development of inhibitors targeting CoV proteases, particularly main proteases (M(pro)s), which could help develop effective treatments to prevent CoV infection. [Image: see text]


id: cord-273608-dxx3p1x5
author: Deng, Jikui
date: 2013-04-11
txt: ./txt/cord-273608-dxx3p1x5.txt
cache: ./cache/cord-273608-dxx3p1x5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-013-3312-y
doi: 10.1007/s12250-013-3312-y
summary:
  Total nucleic acids were extracted using the EZ1 system (Qiagen, Germany) and 17 respiratory viruses and genotypes including influenza A virus (FluA), FluB, parainfluenza virus 1 (PIV1), PIV2, PIV3, PIV4, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinoviruses (RhV), enteroviruses (EnV), human bocaviruses (hBoV), adenoviruses (AdV), four coronaviruses (229E, OC43, NL63 and HKU1), and FluA 2009 pandemic H1N1(H1N1-p) were detected and identified by the ResPlex II kit. In this study, we evaluated the ResPlex II V2.0 kit (Qiagen, Germany), which uses a target enriched multiplexing RT-PCR amplification coupled with a suspension array detection, for detection and identification of a panel of respiratory specimens in pediatric inpatients with LRTIs. Clinical accuracy of the ResPlex II assay was validated on a panel of prospectively collected consecutive nasopharyngeal swab (NPS) specimens in comparison to viral culture and a monoplex real-time TaqMan RT-PCR.

title:
  Respiratory virus multiplex RT-PCR assay sensitivities and influence factors in hospitalized children with lower respiratory tract infections

abstract:
  Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex II V2.0 kit and explored factors influencing its sensitivity. Nasopharyngeal swab (NPS) specimens were prospectively collected from pediatric inpatients with lower respiratory tract infections at the time of admission in the Shenzhen Children’s Hospital from May 2009 to April 2010. Total nucleic acids were extracted using the EZ1 system (Qiagen, Germany) and 17 respiratory viruses and genotypes including influenza A virus (FluA), FluB, parainfluenza virus 1 (PIV1), PIV2, PIV3, PIV4, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinoviruses (RhV), enteroviruses (EnV), human bocaviruses (hBoV), adenoviruses (AdV), four coronaviruses (229E, OC43, NL63 and HKU1), and FluA 2009 pandemic H1N1(H1N1-p) were detected and identified by the ResPlex II kit. In parallel, 16 real-time TaqMan quantitative RT-PCR assays were used to quantitatively detect each virus except for RhV. Influenza and parainfluenza viral cultures were also performed. Among the total 438 NPS specimens collected during the study period, one or more viral pathogens were detected in 274 (62.6%) and 201(45.9%) specimens by monoplex TaqMan RT-PCR and multiplex ResPlex, respectively. When results from monoplex PCR or cell culture were used as the reference standard, the multiplex PCR possessed specificities of 92.9–100.0%. The sensitivity of multiplex PCR for PIV3, hMPV, PIV1 and BoV were 73.1%, 70%, 66.7% and 55.6%, respectively, while low sensitivities (11.1%–40.0%) were observed for FluA, EnV, OC43, RSV and H1N1. Among the seven viruses/genotypes detected with higher frequencies, multiplex PCR sensitivities were correlated significantly with viral loads determined by the TaqMan RT-PCR in FluA, H1N1-p and RSV (p=0.011−0.000). The Qiagen ResPlex II multiplex RT-PCR kit possesses excellent specificity for simultaneous detection of 17 viral pathogens in NPS specimens in pediatric inpatients at the time of admission. The sensitivity of multiplex RT-PCR was influenced by viral loads, specimen process methods, primer and probe design and amplification condition.


id: cord-273712-r2akpce8
author: Wang, Jingjing
date: 2016-02-19
txt: ./txt/cord-273712-r2akpce8.txt
cache: ./cache/cord-273712-r2akpce8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26908211/
doi: 10.1007/s12250-015-3690-4
summary:
  In the same beta group, the receptors for mouse hepatitis virus (MHV) and bovine coronavirus (BCoV) are carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and a sugar, respectively, despite their high sequence homology Peng et al., 2012) . In our study, we compared the efficiency of pseudotyped viruses with S proteins from different groups of CoVs. Furthermore, the cell tropisms of TGEV and PEDV were characterized by live and pseudotyped viruses. Therefore, we compared the S protein amino acid sequences of CoVs from different groups, including SARS-CoV, MHV, HCoV-229E, TGEV, PEDV, HCoV-OC43, BCoV, and IBV (Gen-Bank accession numbers ABD72982.1, AAR92025.1, NP_073551.1, ABG89335.1, NP_598310.1, AAT84362.1, ABM66810.1, and NP_040831.1, respectively) using ClustalW ( Figure 1B ). Lentiviruses pseudotyped with SARS-CoV S protein could efficiently infect 293T cells expressing ACE2, and the pseudovirus level after entry reached 10 6 relative light units (RLU) ( Figure 2B ). To further study the cellular entry of CoVs, we used live PEDV and TGEV to infect different cell lines.

title:
  Comparison of lentiviruses pseudotyped with S proteins from coronaviruses and cell tropisms of porcine coronaviruses

abstract:
  The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins (S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected Vero- CCL-81 (monkey kidney), Huh-7 (human liver), and PK-15 (pig kidney) cells efficiently. CCL94 (cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening. [Image: see text]


id: cord-274785-9jgg8ukr
title: Viral Regulation of RNA Granules in Infected Cells
author: Zhang, Qiang
date: 2019-04-29
txt: ./txt/cord-274785-9jgg8ukr.txt
cache: ./cache/cord-274785-9jgg8ukr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31037644/
doi: 10.1007/s12250-019-00122-3
summary:
  TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. The process of SG formation can be artificially divided into the following steps ( Fig. 2) : (1) accumulation of stalled translation initiation complexes ) in response to various types of stress; (2) the RNA-binding proteins such as RAS-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and T cell-restricted intracellular antigen 1 (TIA1) bind mRNAs and aggregate to nucleate SG formation. SG proteins (eIF4G, eIF3, PABP) are selectively sequestered within Ebola virus inclusion bodies and co-localize with viral RNA to form inclusion body-bound granules, which are functionally and structurally different from canonical SG, probably leading to inhibit the antiviral role of SG (Nelson et al. Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly

abstract:
  RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.


id: cord-284549-edliu3it
title: Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells
author: Zhou, Hui
date: 2019-11-27
txt: ./txt/cord-284549-edliu3it.txt
cache: ./cache/cord-284549-edliu3it.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-019-00182-5
doi: 10.1007/s12250-019-00182-5
summary:
  In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. In this study, we uncovered that HCV nonstructural NS2 protein possessed a potent in vitro VSR activity that suppressed the RNAi induced by short hairpin RNA (shRNA) and siRNA in mammalian cells. Our results showed that the reversal effect of EGFP silencing could be observed at 48 hpt (Fig. 2C) , indicating that the VSR activity was dependent on the expression level of HCV NS2 protein. To investigate whether HCV NS2 can inhibit this step, small RNAs harvested from HEK293T cells co-expressing EGFP-specific shRNA together with NS2 were subjected to Northern blotting with a DIG-labeled RNA probe targeting EGFP siRNA produced from shRNA by Dicer.

abstract:
  RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with double-stranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00182-5) contains supplementary material, which is available to authorized users.


id: cord-295640-mhfu0e9r
author: Wang, Wenling
date: 2019-06-25
txt: ./txt/cord-295640-mhfu0e9r.txt
cache: ./cache/cord-295640-mhfu0e9r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31240620/
doi: 10.1007/s12250-019-00138-9
summary:
  Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. Previously, we expressed a fusion protein of NP and M2e (NM2e) in Escherichia coli and showed that immunization with NM2e formulated with aluminum hydroxide gel protected mice from a lethal challenge with heterologous influenza virus . BALB/c mice were immunized with the recombinant viruses to measure NP-and M2e-specific humoral and cellular immune responses as well as protective effect against lethal challenge with a heterologous influenza virus. Mice immunized with the recombinant vaccinia virus RVJ-NPM2e and RVJ-M2eNP showed strong antibody responses against NP, with lower titers of antibodies against M2e (Fig. 3A) . The recombinant vaccinia virus expressing 4M2e and full-length NP fusion antigen induced strong cross-protection (92%) against a lethal heterosubtypic PR8 challenge at 20 MLD 50 and thus regarded as the optimal one among the four constructs.

title:
  Improving Cross-Protection against Influenza Virus Using Recombinant Vaccinia Vaccine Expressing NP and M2 Ectodomain Tandem Repeats

abstract:
  Conventional influenza vaccines need to be designed and manufactured yearly. However, they occasionally provide poor protection owing to antigenic mismatch. Hence, there is an urgent need to develop universal vaccines against influenza virus. Using nucleoprotein (NP) and extracellular domain of matrix protein 2 (M2e) genes from the influenza A virus A/Beijing/30/95 (H3N2), we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders. The recombinant vaccinia viruses were used to immunize BALB/C mice. Humoral and cellular responses were measured, and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34 (PR8). NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP, while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e. All recombinant viruses elicited NP- and M2e-specific cellular immune responses in mice. Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e. Furthermore, RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD(50) of PR8. Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses, and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00138-9) contains supplementary material, which is available to authorized users.


id: cord-298734-h286m32c
author: Xia, Siyu
date: 2020-06-29
txt: ./txt/cord-298734-h286m32c.txt
cache: ./cache/cord-298734-h286m32c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00253-y
doi: 10.1007/s12250-020-00253-y
summary:
  title: Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. Due to the lack of specific detection of ACE2 mRNA and protein expression in human kidney tubule cells, it is hard to confirm the direct infection of SARS-CoV-2. In this study, we firstly established long term cell cultures of KPTECs using 2D CR and 3D organoids technologies, which maintained the lineage function, and the ability to differentiate and repair DNA damage. In terms of the questions above, we need model systems to study infection of SARS-CoVs in ACE2 expressing cell types, especially in kidney epithelial cells (Hamming et al.

title:
  Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury

abstract:
  The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00253-y) contains supplementary material, which is available to authorized users.


id: cord-300466-sk9iilum
title: Serologic Response to SARS-CoV-2 in COVID-19 Patients with Different Severity
author: Kong, Wen-Hua
date: 2020-07-23
txt: ./txt/cord-300466-sk9iilum.txt
cache: ./cache/cord-300466-sk9iilum.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32705575/
doi: 10.1007/s12250-020-00270-x
summary:
  According to the Chinese Centers for Disease Prevention and Control (CDC) report, among 72,314 COVID-19 cases in China''s mainland most of cases (81%) presented only mild illness or moderate pneumonia, yet 14% developed severe symptoms such as dyspnea, high respiratory frequency and low blood oxygen saturation, and another 5% were in critical conditions like respiratory failure, septic shock, and multiple organ dysfunction/failure (Epidemiology Working Group for NCIP Epidemic Response and Chinese CDC, 2020; Wu and McGoogan 2020) . In this study, we, compared the results of serologic tests and nucleic acid test (NAT) from a group of COVID-19 patients in Wuhan, and analyzed the serologic IgM and IgG antibody level of patients with different disease severity. In summary, this study supported the combination of serologic testing and NAT in routine COVID-19 diagnosis and provided evidence on the temporal profile of antibody response against SARS-CoV-2 in patients with different disease severity.

abstract:
  The immense patient number caused by coronavirus disease 2019 (COVID-19) global pandemic brings the urge for more knowledge about its immunological features, including the profile of basic immune parameters. In this study, eighty-eight reported COVID-19 patients in Wuhan were recruited from January to February, 2020, including 32 severe/critical cases and 56 mild/moderate cases. Their mean age was 56.43 years (range 17–83) and gender ratio (male/female) was 43:45. We tested SARS-CoV-2 RNA with commercial kits, investigated the level of serologic IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using magnetic particle chemiluminescence immunoassays, and compared the results of serologic tests and nucleic acid test (NAT). Among 88 patients, 95.45% were confirmed as positive by the combination of NAT and antibody test, which was significantly higher (P < 0.001) than by single nucleic acid test (73.86%) or serologic test (65.91%). Then the correlation between temporal profile and the level of antibody response was analyzed. It showed that seroconversion started on day 5 after disease onset and IgG level was rose earlier than IgM. Comparison between patients with different disease severity suggested early seroconversion and high antibody titer were linked with less severe clinical symptoms. These results supported the combination of serologic testing and NAT in routine COVID-19 diagnosis and provided evidence on the temporal profile of antibody response in patients with different disease severity.


id: cord-312080-pu6m4qad
title: Three-dimensional cell culture models for investigating human viruses
author: He, Bing
date: 2016-10-27
txt: ./txt/cord-312080-pu6m4qad.txt
cache: ./cache/cord-312080-pu6m4qad.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27822716/
doi: 10.1007/s12250-016-3889-z
summary:
  This review focuses on the recent progress of human virological research with 3D cell culture models, including human viral growth, replication, proliferation, infection, viral life cycle, virus-host interaction and the development of antiviral drugs. A multitude of research has shown that RWV-derived models utilizing human cells are a valuable tool for investigating viral growth, replication, viral infection, viral entry, the viability of virions and virus-host interaction (Margolis et al., 1997; Long et al., 1998; Nickerson et al., 2007; Straub et al., 2007; Barrila et al., 2010; Berto et al., 2013; Goodwin et al., 2015) . As keratinocytes are the main target cells for productive infection in vivo for VZV, characterization of viral replication in organotypic raft cultures of these cells represents a very relevant model for studying virus-host cell interactions and antiviral agents (Andrei et al., 2005) .

abstract:
  Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.


id: cord-315486-pjb5v1tc
title: Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes
author: Wu, Xiaojun
date: 2020-09-30
txt: ./txt/cord-315486-pjb5v1tc.txt
cache: ./cache/cord-315486-pjb5v1tc.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00296-1
doi: 10.1007/s12250-020-00296-1
abstract: nan
summary:
  As expected, COVID-19 patients with health conditions like hypertension or diabetes had a longer length of hospital stay than those without, but this was at the limit of statistical significance (Fig. 1A , P = 0.07). These findings confirmed an increased disease severity in COVID-19 patients with hypertension or diabetes (Liu et al. SARS-CoV-2 infections lead to a fast activation of innate immune cells, especially in COVID-19 patients developing severe disease . These results suggest different mechanisms exist for hypertension or diabetes as risk factors for severe cases of COVID-19. Despite these limitations, we were able to identify different laboratory abnormalities on admission in COVID-19 patients with hypertension or diabetes, which might shed light on future mechanistic studies. Are patients with hypertension and diabetes mellitus at increased risk for covid-19 infection? Risk factors associated with disease severity and length of hospital stay in covid-19 patients


id: cord-319501-a2x1hvkk
title: A molecular arms race between host innate antiviral response and emerging human coronaviruses
author: Wong, Lok-Yin Roy
date: 2016-01-15
txt: ./txt/cord-319501-a2x1hvkk.txt
cache: ./cache/cord-319501-a2x1hvkk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-015-3683-3
doi: 10.1007/s12250-015-3683-3
summary:
  Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. This suggests SARS-CoV N may interfere with RNA recognition by host immune sensors such as RIG-I and MDA5 thus achieving suppressive role in IFN production. Our group demonstrated that MERS-CoV ORF4a interacts with PACT, a cellular dsRNA-binding protein that optimally activates RIG-Iand MDA5-induced type I IFN production, in an RNAdependent manner (Siu et al., 2014c) . Infection with SARS-CoV and MERS-CoV has been accompanied with suppression of innate immune response, most notably with the suppression of type I IFN production and signaling pathways. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses pact-induced activation of RIG-I and MDA5 in the innate antiviral response

abstract:
  Coronaviruses have been closely related with mankind for thousands of years. Communityacquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived. [Image: see text]


id: cord-322005-70snojec
title: Isolation and Growth Characteristics of SARS-CoV-2 in Vero Cell
author: Yao, Pingping
date: 2020-06-19
txt: ./txt/cord-322005-70snojec.txt
cache: ./cache/cord-322005-70snojec.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32562199/
doi: 10.1007/s12250-020-00241-2
abstract: nan
summary:
  title: Isolation and Growth Characteristics of SARS-CoV-2 in Vero Cell In a recent report, 149 mutations were found among 103 sequenced isolates of SARS-CoV-2 . To investigate whether our viruses show mutations different from other reported SARS-CoV-2, all the seven isolates were sequenced at the 3rd passage and the sequences were aligned with coding sequence (CDS) of SARS-CoV-2 Wuhan-Hu-1 (NC_045512). It is interesting to note that these seven patients infected with SARS-CoV-2 have high viral load in the early stage of clinical sign, which is consistent with previous reports (Kim et al. A The cytopathic effect was observed in Vero cells infected with the isolated viruses at 5 dpi. In conclusion, seven SARS-CoV-2 strains were isolated, sequenced and characterized in Vero cells, and a deletion mutation was identified after short passage in Vero cells. Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea SARS-CoV-2 viral load in upper respiratory specimens of infected patients


id: cord-322166-ajolu2rh
title: An overview of the highly pathogenic H5N1 influenza virus
author: Yin, Jingchuan
date: 2013-01-16
txt: ./txt/cord-322166-ajolu2rh.txt
cache: ./cache/cord-322166-ajolu2rh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23325419/
doi: 10.1007/s12250-013-3294-9
summary:
  The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. Disrupted cytokine and chemokine expression, especially IFNs and TNF, and decreased antiviral activity of innate immune response mediators, such as protein kinase resource and retinoic acid-inducible gene product I (RIG-I), directly lead to increased virulence of the virus (Haye K, et al., 2009; Jackson D, et al., 2008; Lipatov A S, et al., 2005; Munir M, et al., 2011) . Thus, patients with H5N1 disease typically present with a hyper-induced systemic inflammatory response syndrome and a higher and a more prolonged viral load in respiratory specimens than other seasonal influenza virus like human H1N1 viruses (Chan M C, et al., 2005; Kuiken T, et al., 2010; Lee D C, et al., 2012; Peiris J S, et al., 2010; Sandbulte M R, et al., 2008) .

abstract:
  Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. This review summarizes the current understanding of, and recent research on, the avian influenza H5N1 virus, including transmission, virulence, pathogenesis, clinical characteristics, treatment and prevention.


id: cord-329876-4cgrjnjo
author: Lei, Jian
date: 2016-05-30
txt: ./txt/cord-329876-4cgrjnjo.txt
cache: ./cache/cord-329876-4cgrjnjo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-016-3742-4
doi: 10.1007/s12250-016-3742-4
summary:
  title: Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. The substrate-binding site of MERS-CoV PL pro features significant differences from those of the corresponding SARS-CoV enzyme and human ubiquitin-specific proteases (USPs, such as, USP14) (Hu et al., 2005; Chou et al., 2014; Ratia et al., 2014) . Hence, we crystallized the ubiquitin (Ub) complex of a MERS-CoV PL pro variant that had the active-site Cys111 replaced by serine (C111S) and determined the structure at 3.16 Å ( Figure 1A ). Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression

title:
  Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin

abstract:
  The papain-like protease (PL(pro)) of Middle-East respiratory syndrome coronavirus (MERS-CoV) has proteolytic, deubiquitinating, and deISGylating activities. The latter two are involved in the suppression of the antiviral innate immune response of the host cell. To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. Five regions of the PL(pro) bind to two areas of the Ub. The C-terminal five residues of Ub, RLRGG, are similar to the P5–P1 residues of the polyprotein substrates of the PL(pro) and are responsible for the major part of the interaction between the two macromolecules. Through sitedirected mutagenesis, we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL(pro). The enzyme appears not to be optimized for catalytic efficiency; thus, replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities. Ubiquitin binding by MERS-CoV PL(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL(pro). The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3742-4 and is accessible for authorized users.


id: cord-332672-fbwz8oxp
author: Wang, Manli
date: 2013-10-30
txt: ./txt/cord-332672-fbwz8oxp.txt
cache: ./cache/cord-332672-fbwz8oxp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24174406/
doi: 10.1007/s12250-013-3402-x
summary:
  It was suggested that the previously known bat SL-CoV stains cannot jump from bats to civets or humans owing to the significant differences between their RBDs (Li F, 2013); 2) although SL-CoVs have been identified from different bat species, isolation of a live SL-CoVs from bats never succeed; 3) no native SL-CoV from bats could use ACE2 as receptors and infect human cells, only when its RBD is replaced with the counterpart from a human SARS-CoV strain (Li W, et al, 2003; Becker M M, et al, 2008; Ren W, et al, 2008) . The residue 479 is known to be an asparagine only in human SAR-CoVs, but not in the previously identified bat SL-CoVs or civet SAR-CoVs. It is proposed that an asparagine at position 479 has a higher binding affinity with human ACE2 and is likely to determine whether the virus can infect humans (Li F, 2013) .

title:
  Bats as animal reservoirs for the SARS coronavirus: Hypothesis proved after 10 years of virus hunting

abstract:
  Recently, the team led by Dr. Zhengli Shi from Wuhan Institute of Virology, Chinese Academy of Sciences, and Dr. Peter Daszak from Ecohealth Alliance identified SL-CoVs in Chinese horseshoe bats that were 95% identical to human SARS-CoV and were able to use human angiotensin-converting enzyme 2 (ACE2) receptor for docking and entry. Remarkably, they isolated the first known live bat SL-CoV that replicates in human and related cells. Their findings provide clear evidence that some SL-CoVs circulating in bats are capable of infecting and replicating in human (Ge X Y, et al., 2013).


id: cord-332861-7b5pzmk6
title: Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases
author: Zhang, Zhan
date: 2020-02-07
txt: ./txt/cord-332861-7b5pzmk6.txt
cache: ./cache/cord-332861-7b5pzmk6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00203-8
doi: 10.1007/s12250-020-00203-8
abstract: nan
summary:
  title: Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases Considering the cause was unknown, we also used drugs to treat atypical pathogens, including moxifloxacin for mycoplasma and chlamydia, and oseltamivir and abidol hydrochloride for influenza A virus; meanwhile, the patient was given Chinese patent medicine Tanreqing iv gtt for adjunctive therapy. We also used drugs to treat atypical pathogens, including moxifloxacin for mycoplasma and chlamydia, and oseltamivir and abidol hydrochloride for influenza A virus; meanwhile, the patient was given Chinese patent medicine Tanreqing iv gtt for adjunctive therapy. On admission, beside fever, the male was predominately manifested by dyspnea and only had mild abnormality in routine urine and stool test results, while the female had obvious gastrointestinal symptoms such as vomiting and diarrhea. In this study, the male had a more severe decrease in immune cells and more severe conditions than the female.


id: cord-333195-m4gvpsf8
author: Lu, Renfei
date: 2020-04-01
txt: ./txt/cord-333195-m4gvpsf8.txt
cache: ./cache/cord-333195-m4gvpsf8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00218-1
doi: 10.1007/s12250-020-00218-1
abstract: nan
summary:
  title: Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Here, we present a novel visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid and sensitive detection of SARS-CoV-2 using mismatch-tolerant technique. The RdRp primers showed higher amplification efficiency, and were selected to establish the SARS-CoV-2 detection assay using the mismatch-tolerant RT-LAMP method Zhou et al. For the POCT diagnosis of SARS-CoV-2 infection in the resource-poor settings, we developed the assay into a visual detection using WarmStart Colorimetric LAMP 2 9 Master Mix (New England Biolabs, Beverly, MA, United States). The sensitivity of the colorimetric RT-LAMP assay for SARS-CoV-2 was 30 copies per reaction, slightly lower than the real-time monitoring (Fig. 1E) . The evaluation with 24 clinical samples showed that all 17 COVID-19 patients in Nantong city were positive for SARS-CoV-2 by both the RT-LAMP and the RT-qPCR assays, showing a full consistence.

title:
  Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2


id: cord-338606-6nk2ij20
title: WSV 2019: The First Committee Meeting of the World Society for Virology
author: Abdel-Moneim, Ahmed S.
date: 2019-12-19
txt: ./txt/cord-338606-6nk2ij20.txt
cache: ./cache/cord-338606-6nk2ij20.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31858457/
doi: 10.1007/s12250-019-00189-y
summary:
  Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25–27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. The World Society for Virology (WSV) was founded in 6 May 2017 and incorporated on 14 December 2017 as a non-profit organization, in the state of Massachusetts in the United States of America. WSV also collaborates with other international organizations and virology societies (Abdel-Moneim et al. The first committee meeting of the WSV was supported by the Swedish Research Council and organized at the Karolinska University Hospital (KUH), Stockholm, Sweden from 25 to 27th August 2019. In the scientific session, there was a series of presentations on different topics of virology: Following these two presentations, a series of sessions concerning the future plans for WSV were conducted. The First Committee Meeting of the World Society for Virology

abstract:
  The World Society for Virology (WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25–27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.


id: cord-348467-a2e3f161
title: Camel exposure and knowledge about MERS-CoV among Australian Hajj pilgrims in 2014
author: Alqahtani, Amani Salem
date: 2016-01-18
txt: ./txt/cord-348467-a2e3f161.txt
cache: ./cache/cord-348467-a2e3f161.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-015-3669-1
doi: 10.1007/s12250-015-3669-1
abstract: [Image: see text]
summary:
  Most departing pilgrims (62%) were aware of a mod-erate to high infection risk from raw camel milk consumption, yet 21% of participants were willing to drink it. Nevertheless, among those who were aware of MERS-CoV, 27% did not fully realize the risk of catching the disease from unpasteurized camel milk, 15% were willing to drink raw camel milk, and 23% were keen to visit camel farm in Saudi Arabia (Table 3) . A unique finding to emerge from our study was that departing pilgrims with knowledge about MERS-CoV were significantly more aware of the risk of drinking raw camel milk (43% vs. Therefore, pilgrims who consume raw milk or other products are at risk of other zoonotic diseases if not MERS-CoV, and therefore, could benefit from appropriate health education.


id: cord-352988-9ey3ir5e
author: Xiang, Yang-fei
date: 2010-10-08
txt: ./txt/cord-352988-9ey3ir5e.txt
cache: ./cache/cord-352988-9ey3ir5e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20960184/
doi: 10.1007/s12250-010-3144-y
summary:
  A polyphenolic compound, 1,2,4,6-tetra-O-galloyl-β-D-glucose (1246TGG), was isolated from the traditional Chinese medicine Phyllanthus emblica L. Results indicates that treatment with 1246TGG (6.25 μg/mL, 3.13 μg/mL), reduced both HBsAg and HBeAg levels in culture supernatant, yet the inhibitory effects tend to decline with the assay time. Here, we investigated the anti-HBV activity of 1246TGG by detecting the HBsAg and HBeAg secretion levels in HepG2.2.15 cell culture, a cell line derived by transfection of cloned HBV DNA into human hepatoblastoma cell line HepG2 and used to assay for anti-HBV agents [4] . To determine the inhibitory effects of 1246TGG on HBV antigen secretion, cells were treated with 1246TGG at concentrations of 6.25µg/mL and 3.13µg/mL every 3 d during the 10 d treatment period. A cell culture assay for compounds which inhibit hepatitis B virus replication

title:
  Effects of 1,2,4,6-tetra-O-galloyl-β-D-glucose from P. emblica on HBsAg and HBeAg secretion in HepG2.2.15 cell culture

abstract:
  A polyphenolic compound, 1,2,4,6-tetra-O-galloyl-β-D-glucose (1246TGG), was isolated from the traditional Chinese medicine Phyllanthus emblica L. (Euphorbiaceae) and assayed for its potential as an anti-hepatitis B virus (HBV) agent. The cytotoxicity of 1246TGG on HepG2.2.15 as well as HepG2 cells was determined by observing cytopathic effects, and the effects of 1246TGG on secretion of HBsAg and HBeAg in HepG2.2.15 cells were assayed by enzyme immunoassay. Results indicates that treatment with 1246TGG (6.25 μg/mL, 3.13 μg/mL), reduced both HBsAg and HBeAg levels in culture supernatant, yet the inhibitory effects tend to decline with the assay time. This study provides a basis for further investigation of the anti-HBV activity and possible mechanism of action of 1246TGG.


id: cord-354529-k8p2u7iq
author: Wu, Yongran
date: 2020-08-31
txt: ./txt/cord-354529-k8p2u7iq.txt
cache: ./cache/cord-354529-k8p2u7iq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32865701/
doi: 10.1007/s12250-020-00281-8
summary:
  Clinical information of patients was collected from the electronic medical information system of Jinyintan Hospital, including the following factors: demographic data; date of symptom onset, admission, first CP infusion and discharge; laboratory data before and after infusion of CP, including white blood cell count, neutrophil count, lymphocyte count, liver and kidney function test, and inflammatory factors such as high sensitive C-reaction protein (HsCRP); results of SARS-CoV-2 test and cycle threshold value (Ct value) of quantitative reverse transcription-polymerase chain reaction; patients'' status and treatments before or after the CP therapy, including the vital signs, anti-virus therapy, oxygen therapy, and other treatments; total volume dose of CP; pulmonary imaging examination data; information on complications such as transfusion-related adverse reactions. Clinical Benefit and Outcome of Patients with Prolonged Positivity of SARS-CoV-2 RNA after CP Therapy As shown in Table 3 , the median and interquartile ranged total volume of CP transfusion was 400 (200-400) mL in EN group and 400 (400-800) mL in LN group.

title:
  Patients with Prolonged Positivity of SARS-CoV-2 RNA Benefit from Convalescent Plasma Therapy: A Retrospective Study

abstract:
  Convalescent plasma therapy has been implemented in a few cases of severe coronavirus disease 2019. No report about convalescent plasma therapy in treating patients with prolonged positivity of SARS-CoV-2 RNA has been published. In this study, we conducted a retrospective observational study in 27 patients with prolonged positivity of SARS-CoV-2 RNA, the clinical benefit of convalescent plasma therapy were analyzed. qRT-PCR test of SARS-CoV-2 RNA turned negative (≤ 7 days) in a part of patients (early negative group, n = 15) after therapy, others (late negative group, n = 12) turned negative in more than 7 days. Pulmonary imaging improvement was confirmed in 7 patients in early negative group and 8 in late negative group after CP therapy. Viral load decreased in early negative group compared with late negative group at day 3, 5, 7 after implementing convalescent plasma therapy. Patients in early negative group had a shorter median length of hospital stay. In conclusion, convalescent plasma therapy might help eliminate virus and shorten length of hospital stay in patients with prolonged positivity of SARS-CoV-2 RNA.


id: cord-356154-ifb3qiz7
title: A Study of Two Cases Co-Infected with SARS-CoV-2 and Human Immunodeficiency Virus
author: Zhang, Rong
date: 2020-09-07
txt: ./txt/cord-356154-ifb3qiz7.txt
cache: ./cache/cord-356154-ifb3qiz7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s12250-020-00280-9
doi: 10.1007/s12250-020-00280-9
abstract: nan
summary:
  CT scan results in early February indicated lesions in bilateral lungs (Supplementary Table S1 ), but the result of the SARS-CoV-2 nucleic acid test was negative. However, the patient''s condition deteriorated again on February 20, and the nucleic acid test results were single positive for COVID-19 SARS-CoV-2. Notes: ND, no data; ?, positive; -, negative We assumed that HIV infection had damaged their immune systems; this could also explain why the patient tested negative for SARS-CoV-2 antibodies in the late stages of treatment when the disease became worse. In general, the blocking of the IL-6 receptor with tocilizumab has a particular effect on the treatment of COVID-19 patients with severe disease, but it may have little effect on patients with Fig. 1 The clinical courses of two cases co-infected with SARS-CoV-2 and HIV. COVID-19 patients with immunodeficiency disease may cause more severe illness and poor treatment response due to the destruction of the immune system.


