Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 70 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 605 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 53 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 14 RNA 12 SARS 11 Fig 10 virus 7 cell 4 MERS 4 HCV 3 dna 3 Vero 3 TGEV 3 IFN 3 HIV-1 3 HIV 3 HBV 2 influenza 2 infection 2 extract 2 antiviral 2 activity 2 ZIKV 2 University 2 USA 2 RSV 2 RBD 2 PEDV 2 Institute 2 FIPV 2 Ebola 2 East 2 ELISA 2 CD8 1 yeast 1 vaccine 1 sting 1 slice 1 site 1 rotavirus 1 rig 1 respiratory 1 q7r 1 lung 1 interferon 1 hsv-1 1 dengue 1 compound 1 chloroquine 1 Zika 1 WNV 1 Virology 1 VP2 Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 4271 virus 3768 cell 1939 infection 1584 protein 1433 activity 1098 % 960 effect 943 mouse 900 study 857 treatment 849 replication 791 compound 767 drug 717 influenza 706 assay 705 h 657 group 653 day 616 concentration 602 peptide 583 inhibitor 583 antibody 582 coronavirus 556 result 521 vaccine 520 disease 507 c 487 inhibition 477 control 463 type 463 level 462 acid 459 strain 435 time 434 gene 429 expression 412 structure 412 response 392 ml 390 receptor 386 agent 384 model 380 lung 366 entry 364 datum 357 sequence 357 culture 349 mechanism 346 analysis 322 g Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 3248 al 3137 . 2609 et 1002 Fig 915 RNA 773 SARS 612 CoV 471 RSV 398 C 371 MERS 326 HIV 323 M 279 TGEV 266 IFN 265 HCV 246 Vero 246 HIV-1 231 mg 230 T 218 PCR 217 USA 208 ARB 207 N 194 B 192 L 187 A 186 siRNA 178 HBV 177 PBS 175 PPMO 167 HSV 162 University 159 PRRSV 156 CD8 152 Ebola 147 Hiltonol 144 G 143 PEDV 138 RT 138 GP 135 myricetin 131 RNase 128 S 126 Middle 125 East 124 Research 123 CoV-2 121 kg 118 DNA 117 Table Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 968 we 780 it 233 i 209 they 58 them 29 itself 23 us 21 he 18 one 9 me 5 she 5 m27f 4 you 4 themselves 3 nr-818 3 es/2001 2 him 2 he16 1 sifitm3 1 sgp 1 mrnas 1 mg 1 leu443 1 hpiv1 1 hdp-(s)-hpmpa 1 3cwt Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 13121 be 1858 have 1398 use 1066 show 775 inhibit 678 infect 542 treat 505 bind 469 induce 433 contain 396 determine 383 suggest 382 indicate 381 reduce 380 do 342 observe 336 base 333 follow 332 include 325 describe 296 evaluate 296 compare 291 find 288 target 283 express 282 report 274 cause 269 increase 265 perform 265 identify 265 add 264 incubate 260 demonstrate 247 test 232 result 228 mediate 224 provide 222 develop 221 require 209 associate 200 block 199 measure 187 analyze 186 detect 183 lead 180 obtain 178 involve 171 exhibit 164 neutralize 164 confirm Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1522 viral 1326 - 1258 antiviral 1027 not 747 anti 742 also 734 human 718 respiratory 528 other 521 high 452 specific 384 well 363 however 360 different 343 clinical 339 more 336 further 333 such 332 respectively 325 then 323 only 316 low 310 cellular 301 effective 288 inhibitory 286 new 266 severe 259 non 256 significant 253 first 252 acute 252 active 237 most 233 dependent 228 previously 227 similar 227 novel 223 significantly 220 highly 219 infectious 219 infected 215 thus 213 therapeutic 213 several 208 as 207 immune 198 early 193 structural 187 important 182 single Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 69 most 36 least 32 high 26 good 23 Most 10 late 9 large 6 low 3 long 3 great 3 fast 2 tt 2 preS1 2 early 2 close 1 young 1 weak 1 small 1 short 1 narrow 1 hexose 1 Pro229 1 Least 1 -d 1 -actin 1 -O Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 168 most 46 least 3 well 2 highest 1 long Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 8 dx.doi.org 5 doi.org 4 dx 4 arbidol.org 2 www.syfpeithi.de 2 www.gvn.org 2 www-bimas.cit.nih.gov 2 clinicaltrials.gov 1 www.who.int 1 www.virologycongress.com 1 www.sjzsiyao.com 1 www.siga.com 1 www.janssen.com 1 www.isar-icar.com 1 www.eliminatedengue.com 1 www.chimerix-inc.com 1 www.chemeurope.com 1 www.ccalfandegaporto.com 1 www.btsmeetings.com 1 www.arbidol.org 1 www 1 who-blueprint-mapping-tool.surge.sh 1 multalin.toulouse.inra.fr 1 motif-x.med.harvard.edu 1 img1.guidechem.com 1 gvn.org 1 espript.ibcp.fr 1 drugvirus.info 1 depond.b2bage.com 1 cellsymposia.com Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 4 http://dx 2 http://www.syfpeithi.de/ 2 http://www.gvn.org 2 http://www-bimas.cit.nih.gov/molbio/hla 2 http://arbidol.org/rat.html 1 http://www.who.int/csr/ 1 http://www.virologycongress.com 1 http://www.sjzsiyao.com/products_detail/&productId=46.html 1 http://www.siga.com/?ID=65 1 http://www.janssen.com/partnerships/dengue 1 http://www.isar-icar.com 1 http://www.eliminatedengue.com 1 http://www.chimerix-inc.com/pdfs 1 http://www.chemeurope.com/en/encyclopedia/Arbidol.html 1 http://www.ccalfandegaporto.com/en 1 http://www.btsmeetings.com/zika 1 http://www.arbidol.org/arbidol-patent-2004-sars-russian.pdf 1 http://www 1 http://who-blueprint-mapping-tool.surge.sh/ 1 http://multalin.toulouse.inra.fr/multalin/ 1 http://motif-x.med.harvard.edu/ 1 http://img1.guidechem.com/msdspdf/131707-23-8.pdf 1 http://gvn.org/sapporo_2016 1 http://espript.ibcp.fr/ESPript/ESPript/ 1 http://dx.doi.org/10.1016/j.antiviral.2015.05.008 1 http://dx.doi.org/10.1016/j.antiviral.2015.05 1 http://dx.doi.org/10.1016/j.antiviral.2015.03.016 1 http://dx.doi.org/10.1016/j.antiviral.2015.03 1 http://dx.doi.org/10.1016/j.antiviral.2014.02.002 1 http://dx.doi.org/10.1016/j.antiviral.2014.01.021 1 http://dx.doi.org/10.1016/j.antiviral.20 1 http://dx.doi.org/10.1016/j.antiviral 1 http://drugvirus.info 1 http://doi.org/10.1093/nar/gkv367 1 http://doi.org/10.1016/j.antiviral.2020.104742 1 http://doi.org/10.1016/j.antiviral.2020.104714 1 http://doi.org/10.1016/j.antiviral.2018.10.028 1 http://doi.org/10.1016/j.antiviral.2018.09.002 1 http://depond.b2bage.com/product-chemical-auxiliary-agent/ 1 http://clinicaltrials.gov/show/ 1 http://clinicaltrials.gov/ct2/show/ 1 http://cellsymposia.com/emerging-viruses-2017 1 http://arbidol.org/pre-1990-animal-human-test-results.pdf 1 http://arbidol.org/arbidol-childrens-study.pdf Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 1 zmelk@lf1.cuni.cz 1 pink@rpm.fmrp.usp.br 1 lieve.naesens@kuleuven.be 1 jclin@mail.tcu.edu.tw 1 info@isaricar.com 1 dhkwon@kribb.re.kr 1 amy.patick@pfizer.com 1 livonesi@zipmail.com.br Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 28 cells were then 11 cells were mock 8 cells were further 7 cells were first 6 cells were co 5 cells were also 5 compounds did not 5 cov infected mice 5 mice did not 5 virus infected cells 4 activity was also 4 cells were cultured 4 peptides were then 4 rna was not 3 cells did not 3 cells were kindly 3 infection did not 3 mice were randomly 3 peptides do not 3 protein is not 3 virus was not 2 activity was completely 2 activity was dependent 2 activity was not 2 assay does not 2 assays using recombinant 2 assays were then 2 cells has not 2 cells is not 2 cells using plaque 2 cells using trizol 2 cells was also 2 cells was efficiently 2 cells were completely 2 cells were not 2 cells were routinely 2 cells were seed 2 cells were significantly 2 cells were still 2 compound did not 2 compounds were active 2 compounds were also 2 compounds were non 2 cov is endemic 2 cov using computational 2 drugs are highly 2 drugs do not 2 effect is independent 2 effect was not 2 groups showed relatively Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 2 cells did not significantly 1 % were not sure 1 . did not obviously 1 activity was not sufficient 1 assays showed no cytotoxicity 1 cells are not usually 1 cells has not yet 1 cells is not due 1 compound is not due 1 compounds are not cytotoxic 1 concentration is not toxic 1 cov showed no significant 1 day was not protective 1 drugs find not sufficient 1 effect is not due 1 effect was no longer 1 effect was not fully 1 groups are not specific 1 infection does not directly 1 infection had no antiviral 1 infection had no impact 1 infection is not yet 1 peptide is not necessary 1 peptides did not adversely 1 protein is not present 1 replication is not completely 1 rna is not efficient 1 rna was not detectable 1 rna was not significantly 1 study is not possible 1 treatment did not significantly 1 treatment is not easily 1 virus induced no significant 1 virus is not capable 1 virus was not highly 1 viruses is not yet A rudimentary bibliography -------------------------- id = cord-278876-il7g78w1 author = Akkina, Ramesh title = 2016 International meeting of the Global Virus Network date = 2017-03-16 keywords = Ebola; GVN; HIV; Institute; University; cell; virus summary = This report highlights the accomplishments of GVN researchers in many priority areas of medical virology, including the current Zika epidemic, infections by human papillomavirus, influenza, Ebola, Lassa, dengue, HIV, hepatitis C, and chikungunya viruses, and the development of improved diagnostics and new vaccines. This meeting report highlights accomplishments of GVN researchers in many priority areas of human virology, including the current Zika epidemic, infections by human papillomavirus, influenza, Ebola, Lassa, dengue, HIV, hepatitis C and chikungunya viruses, and the development of improved diagnostics and new vaccines. The main objectives of the meeting were to present and discuss current findings in medical virology, including advances in research on HIV vaccines and other important retroviruses; provide a framework to encourage collaborations among world experts; and address the GVN''s annual strategy for continued development. Hideki Hasegawa, a GVN center director at the National Institute of Infectious Diseases in Tokyo, explained that secretory IgA antibodies on mucosal surfaces play an important role in protection against influenza virus infection. doi = 10.1016/j.antiviral.2017.03.005 id = cord-255536-x1z2o9gs author = Artusi, Sara title = The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand date = 2015-04-03 keywords = BRACO-19; HSV-1; dna summary = The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. In the Epstein-Barr herpes virus (EBV), G-quadruplexes modulate EBV nuclear antigen 1 (EBNA1) activity and translation (Murat et al., 2014) ; in particular, BRACO-19 inhibited EBNA1-dependent stimulation of viral DNA replication http://dx.doi.org/10.1016/j.antiviral.2015.03.016 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. We demonstrate that treatment with the G-quadruplex ligand BRACO-19 greatly stabilizes these sequences resulting in decrease of infectious viral particles, reduction of late viral transcripts, inhibition of Taq polymerase processing at the HSV-1 genome, specifically affecting viral DNA replication at G-quadruplex regions. doi = 10.1016/j.antiviral.2015.03.016 id = cord-329494-cdn52epy author = Artuso, María C. title = Inhibition of Junín virus replication by small interfering RNAs date = 2009-07-08 keywords = JUNV; RNA; Vero summary = The efficacy of this Z2-siRNA against JUNV was also demonstrated in virus-infected cells, by testing infectious virus plaque formation (92.8% JUNV yield reduction), viral RNA level or antigen expression, as well as in cells transfected with Z-specific reporter plasmids (91% reduction in expression of Z-EGFP fusion protein). (E) Expression of viral antigens in Vero cells transfected with Z2-siRNA or X-siRNA and infected with JUNV was detected by immunofluorescence assay using a rabbit anti-JUNV polyclonal serum. The efficacy of this agent against JUNV was also demonstrated in virus-infected cells by testing infectious virus plaque formation, viral RNA or antigen expression, as well as in cells transfected with Z-specific reporter plasmids. The present study represents the first report of virus inhibition mediated by RNA interference for a New World arenavirus, a group in the family including four agents of severe viral hemorrhagic fevers in South America (JUNV, Machupo, Sabiá and Guanarito viruses). doi = 10.1016/j.antiviral.2009.07.001 id = cord-008761-b36x05fn author = Billiau, A. title = The interferon system as a basis for antiviral therapy or prophylaxis date = 2012-02-26 keywords = IFN; interferon summary = Possessing satisfactory answers to these questions is essential, not only to understand the natural role of the interferon system in virus disease but also to assess possible applications in medicine, in particular the use of interferons or interferoninducing substances as antiviral drugs. Interferon prepared from mouse cell lines infected with Newcastle disease virus is a mixture of a and B (6) . The main difference between these products and their natural-source-derived counterparts is that they contain only a single subtype, namely a2'' While it is known that different subtypes of HuIFN-~ may differ in their antiviral potency depending on the cells on which they are tested, it is not yet known whether this has any repercussion for the clinical effects. Although these side-chains do not playa significant role in the effects of the IFN-S on cells, the pharmacokinetic behavior of this rDd-IFN-S was found to be rather different from that of natural fibroblast-derived interferon (8) . doi = 10.1016/s0166-3542(85)80020-6 id = cord-253825-d9borky8 author = Blaising, Julie title = Arbidol as a broad-spectrum antiviral: An update date = 2014-04-24 keywords = ARB; HCV; antiviral; virus summary = ARB has been shown to display antiviral in vitro and/or in vivo activity against a number of enveloped or non-enveloped RNA or DNA viruses, including influenza viruses A, B and C , respiratory syncytial virus, SARS-CoV, adenovirus, parainfluenza type 5, poliovirus 1, rhinovirus 14, coxsackievirus B5, hantaan virus, Chikungunya virus, HBV and HCV [reviewed in Boriskin et al. Shi and coworkers showed a greater inhibitory effect on influenza A H1N1 when ARB was added before infection or when it was pre-incubated with the virus (Shi et al., 2007) , suggesting that membrane impregnation and/or metabolites could underlie ARB antiviral activity (see Section 6.). Recently, Tannock and coworkers reported a potent antiviral activity of ARB on several virus families responsible of respiratory infections in animals and humans, in particular on influenza A H3N2 (IC50 12 lM), and the non-enveloped Picornaviridae poliovirus 1 and rhinovirus 14 (Brooks et al., 2012 ; see also Brooks et al., 2004) . doi = 10.1016/j.antiviral.2014.04.006 id = cord-284655-zemns7wd author = Calvo-Pinilla, Eva title = Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48 h before, or 48 h after challenge date = 2015-01-30 keywords = AHSV; MVA; VP2 summary = Previous studies show that a recombinant modified vaccinia Ankara (MVA) virus expressing VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against challenge. Follow up experiments indicated that passive transfer of antiserum, from MVA-VP2 immune donors to recipient mice 1 h before challenge, conferred complete clinical protection and significantly reduced viraemia. In this paper, follow-up studies investigating the relative contribution of humoral and cell-mediated immunity to the protection conferred by MVA-VP2 vaccination, using passive immunisation of naïve recipient IFNAR À/À mice with splenocytes or antiserum from MVA-VP2 vaccinated mice, are described. Vaccination of mice with a modified Vaccinia Ankara (MVA) virus expressing the African horse sickness virus (AHSV) capsid protein VP2 induces virus neutralising antibodies that confer protection against AHSV upon passive immunisation doi = 10.1016/j.antiviral.2015.01.009 id = cord-314833-6fue84x6 author = Chang, Chung-ke title = The SARS coronavirus nucleocapsid protein – Forms and functions date = 2014-01-11 keywords = CTD; NTD; RNA; RNP; SARS summary = doi = 10.1016/j.antiviral.2013.12.009 id = cord-315524-vgdjpjkj author = Chen, Sunrui title = Drug screening identifies gemcitabine inhibiting rotavirus through alteration of pyrimidine nucleotide synthesis pathway date = 2020-05-30 keywords = Fig; rotavirus summary = We identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of rotavirus infection. Supplementation of UTP or uridine largely abolished the anti-rotavirus activity of gemcitabine, suggesting its function through inhibition of pyrimidine biosynthesis pathway. Furthermore, immunofluorescent staining of viral capsid protein (VP6) showed significant reduction of the number of infected Caco2 cells by gemcitabine treatment (Fig. 1F, 1G, Supplementary Fig. S2 ). Our previous studies have evaluated the effects of the nucleoside analog ribavirin and mycophenolic acid (MPA), and the antiviral cytokine interferon alpha (IFN-α) on rotavirus in cell culture models. We have previously established modeling of rotavirus infection in intestinal organoids, which allows the study of virus-host interactions and assessment of antiviral drugs (Yin et al., 2015a; Yin et al., 2018a; Yin et al., 2018b; Yin et al., 2016) . Gemcitabine, a widely used anti-cancer drug, has potent antiviral activity against rotavirus infection Gemcitabine exerts its anti-rotavirus effect through inhibiting pyrimidine biosynthesis pathway doi = 10.1016/j.antiviral.2020.104823 id = cord-286831-ni7qfjk9 author = Choi, Hwa-Jung title = Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus date = 2008-11-06 keywords = PEDV; q7r summary = Following this, 0.09 mL of diluted virus suspension of PEDV containing CCID 50 (50% cell culture infective dose) of the virus stock to produce a appropriate cytopathic effects within 2 days after infection and 0.01 mL of medium supplemented with typsin-EDTA containing an appropriate concentration of the compounds were added. Current antiviral drugs, natural compounds and flavonoids were further studied for their inhibitory effects on replication of the PEDV and cytotoxicity in Vero cells, among which ribavirin, tannic acid, coumarin and interferon-␣ exhibited the activities with IC 50 of 4.1, 47.4, 9 g/mL and 0.52 unit, respectively. A similar result was obtained in control infections with treated ribavirin (Fig. 1 ), but antiviral activity was shown to be lower than that of Q7R. Trials of ribavirin in this study showed that the drug had favorable effects on antiviral activity in Vero cells infected with PEDV. doi = 10.1016/j.antiviral.2008.10.002 id = cord-256270-7e8zlt3t author = Choy, Ka-Tim title = Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro date = 2020-04-03 keywords = SARS summary = We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Among the 16 compounds we tested, remdesivir, lopinavir, homoharringtonine, and emetine dihydrochloride were found to inhibit SARS-CoV-2 replication in Vero E6 cells with EC 50 under 100 μM (Table 1) . Importantly, we observed that some of the compounds currently undergoing clinical trials such as ribavirin, favipiravir, oseltamivir, or baloxavir showed no apparent antiviral effect against the SARS-CoV-2 virus in vitro at concentrations under 100 μM (Table 1) . doi = 10.1016/j.antiviral.2020.104786 id = cord-336517-v7z62tld author = Chu, Hsu-Feng title = Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine date = 2018-08-20 keywords = PEDV; PL2; SARS summary = Further studies suggest that PEDV PL2 pro exhibits much higher DUB activity than that of SARS-and MERS-CoV PL pro s and can be inhibited by the anti-leukemia drug 6-thioguanine (6TG). Previous studies suggested that the Ubl domain was not involved in the catalytic activity of SARS-and MERS-CoV PL pro s (Chou et al., 2012; Clasman et al., 2017) . Overall, the secondary, tertiary and quaternary structures of the PEDV PL2 pro catalytic core are similar to those of SARS-and MERS-CoV PL pro s, even though their sequence identity is only 22-25% (Fig. S1 ). In contrast, previous studies suggested that the binding site of 6TG for SARS-and MERS-CoV PL pro s may be near the catalytic triad''s cysteine residue due to its competitive pattern of inhibition Chou et al., 2008) . Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin doi = 10.1016/j.antiviral.2018.08.011 id = cord-300117-rlpzejjt author = Coutard, B. title = The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade date = 2020-02-10 keywords = SARS; site summary = In the case of human-infecting coronaviruses such as HCoV-OC43 (Le Coupanec et al., 2015) , MERS-CoV (Millet and Whittaker, 2014) , and HKU1 (Chan et al., 2008) the spike protein has been demonstrated to be cleaved at an S1/S2 cleavage site (Fig. 2) generating the S1 and S2 subunits. The furin-like S2′ cleavage site at KR↓SF with P1 and P2 basic residues and a P2′ hydrophobic Phe (Seidah and Prat, 2012) , downstream of the IFP is identical between the 2019-nCoV and SARS-CoV (Fig. 2) . However, in the other less pathogenic circulating human CoV, the S2′ cleavage site only exhibits a monobasic R↓S sequence (Fig. 2) with no basic residues at either P2 and/or P4 needed to allow furin cleavage, suggesting a less efficient cleavage or higher restriction at the entry step depending on the cognate proteases expressed by target cells. doi = 10.1016/j.antiviral.2020.104742 id = cord-295470-mua0qvst author = Cui, Zhanding title = Nitazoxanide Protects Cats from Feline Calicivirus Infection and Acts Synergistically with Mizoribine in vitro date = 2020-06-21 keywords = FCV; MZR; NTZ summary = In this study, we showed that both nitazoxanide and mizoribine had antiviral activity in F81 cells infected with different strains of FCV and also demonstrated a synergistic effect between the two drugs. (C and D) Virus TCID 50 values were calculated to determine the combined effect of different concentrations of NTZ (0-2.5 μM) and MZR (0-20 μM) on FCV. NTZ and MZR not only had antiviral efficacy against the FCV CH-JL2 strain, but the TCID 50 values of the CH-JL1, CH-JL3, CH-JL4 and CH-SH strains were also significantly different after drug treatment (p < 0.0332) (Figure 2A ). After oral NTZ treatment, either on -1 dpi or 3 dpi, levels of FCV in the trachea and lungs were significantly lower than in the control group (p < 0.0002) ( Figure 4F ). NTZ was shown to reduce viral load in the trachea and lungs and still had a therapeutic effect on FCV-infected cats when administered at 3 dpi. doi = 10.1016/j.antiviral.2020.104827 id = cord-297398-40bshqly author = Dong, Wanyu title = Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways date = 2019-11-18 keywords = DMSO; Fig; MAPK; PK-15; TGEV summary = To compare antiviral potencies, PK-15 cells were infected with TGEV at an MOI of 0.1 and then treated with DMSO or compounds at various concentrations, and the virus yield in the supernatants was determined at 36 hpi ( Fig. 1C and E). To explore whether the antiviral activity of A9 is affected by the cell type or virus-to-cell ratio, viral inhibition assays were performed in epithelial and fibroblast derived cell types and at various MOIs. Both PK-15 and ST cells were treated with A9 or vehicle control (DMSO) and infected with TGEV at an MOI of 0.01, 0.1, or 1. To explore whether A9 affects TGEV replication by inhibiting downstream mediators of the p38 or JNK MAPK pathways, we treated TGEV-infected PK-15 cells with the specific inhibitor BIRB796 or DB07268 and determined the toxicity of inhibitors in PK-15 cells using the MTT assay. doi = 10.1016/j.antiviral.2019.104651 id = cord-297531-et1sli23 author = Du, Ruikun title = A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex virus date = 2017-10-20 keywords = 21c11; Fig; HSV-2; Vero; cell summary = Our current investigation found a mAb, m27f that recognizes a new continuous epitope (residues 292 to 297) within the pro-fusion domain of HSV and possesses a high level of virus-neutralizing activity. Briefly, virusantibody mixture was incubated for 1 h at 4°C before inoculating over the Vero cells (pre-attachment), while prechilled (4°C for 15 min) Vero cells were infected with HSV-1 or HSV-2 (100 pfu/well) at 4°C for 1 h to allow virus adsorption before serial dilutions of antibodies were added (post-attachment). After 2 h of adsorption at 37°C, the virus inoculum was removed and cells were washed with PBS twice then incubated in DMEM containing 2% FBS in the presence of antibodies, m27f (500 μg/ml) and 21C11 (500 μg/ml), mouse IgG (500 μg/ml), or medium alone as a control. As shown in Fig. 4A , m27f completely inhibited cell-to-cell spread of both HSV-1 and HSV-2, as evidenced by observing the limited fluorescence caused by virus infection. doi = 10.1016/j.antiviral.2017.10.013 id = cord-270364-lsfmcj5c author = Geller, C. title = Antiseptic properties of two calix[4]arenes derivatives on the human coronavirus 229E() date = 2010-09-18 keywords = C[4]S summary = Comparing these results with some obtained previously with chlorhexidine and hexamidine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C[4]S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C[4]S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4 log 10 reduction in viral titer after 5 min of contact with 10 −3 mol L −1 solutions of C[4]S-BTZ and chlorhexidine, respectively. Comparing these results with some obtained previously with chlorhexidine and hexamidine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C[4]S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C[4]S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4 log 10 reduction in viral titer after 5 min of contact with 10 −3 mol L −1 solutions of C[4]S-BTZ and chlorhexidine, respectively. doi = 10.1016/j.antiviral.2010.09.009 id = cord-298938-xemarhlv author = Goswami, Biswendu B. title = Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2′–5′ oligoadenylate synthetase date = 2004-04-07 keywords = HAV; IFN; RNA; cell summary = title: Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2′–5′ oligoadenylate synthetase We have presented previously evidence that the cytopathogenic 18f strain of hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected cells [Arch. Based on the pattern of rRNA degradation in intact ribosomes, we suggested that the 18f virus activates the interferon (IFN) controlled 2 -5 oligoadenylic acid-dependent RNase L pathway (for recent reviews, see Stark et al., 1998; Barber, 2001; Sen, 2001) . First, the level of IFN, 2 -5 OAS and RNase L mRNAs were investigated by RT-PCR to determine if any of these RNAs were induced following virus infection (Fig. 8) . RT-PCR amplification of selected cellular and viral mRNAs. Two microgram of RNA isolated from virus infected, IFN-␤, or dsRNA treated cells were reverse transcribed in a volume of 20 l using oligo(dT) 15 as primer as described in Section 2. doi = 10.1016/j.antiviral.2004.02.004 id = cord-288337-sw7xjpbr author = Guo, Chao-Tan title = Edible bird''s nest extract inhibits influenza virus infection date = 2006-03-03 keywords = EBN; extract summary = Five microliters of influenza virus suspension (500 ng protein) in 50 mM sodium acetate buffer (pH 5.5) containing two-fold serial dilution of the EBN extracts was stored at 37 • C for 30 min and then incubated with 5 l of 4 mM 2 -(4-methylumbelliferyl)-␣-d-N-acetylneuraminic acid (4-MU-Neu5Ac) (Sigma-Aldrich, St. Louis, MO) at 37 • C for 30 min. In order to check the reaction of EBN extract with influenza viruses, we used the human influenza virus strain A/Aichi/2/68 (H3N2), which bound to both sialyl ␣2-3 and ␣2-6 galactose linkages in salylglycoproteins and sialylglycolipids, and carried out an SDS-PAGE Western blotting assay to analyze the glycoprotein molecules. As shown in Fig. 2A , in case of no treatment with the pancreatic enzyme, neither the EBN extract from S1 nor that from S2 inhibited the hemagglutination of influenza A virus (strain A/Aichi/2/68) to human type O erythrocytes. doi = 10.1016/j.antiviral.2006.02.005 id = cord-010247-cug21fnf author = Hollingshead, Melinda G. title = An ELISA system for evaluating antiretroviral activity against Rauscher murine leukemia virus date = 1992-06-15 keywords = ELISA summary = A system for evaluating the activity of antiviral agents against Rauscher murine leukemia virus (R-MuLV) has been developed using an enzyme linked immunosorbent assay technique. The assay is based upon detection of R-MuLV encoded p30 protein production in virus infected murine cells. Cytotoxicity evaluations are conducted in parallel to the Rauscher MuLV ELISA assay in order to assess drug-induced reductions in cell viability. Cytotoxicity evaluations are important to interpretation of the ELISA results since reductions in cell viability reduce viral protein production which would indicate an antiviral drug effect. In the case of this compound, the activity detected by the UV-XC plaque reduction assay was believed to result from cytotoxicity to the XC cells used as an overlay. The primary difference between the-ELISA assay and the UV-XC plaque reduction assay is in the drug concentrations required to suppress the virus production endpoint. The UV-XC plaque reduction assay measures the capacity of an antiviral compound to reduce production of infectious virus. doi = 10.1016/0166-3542(92)90060-i id = cord-281069-m638nyt0 author = Hong, Wei title = Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1 date = 2013-12-04 keywords = Hp1036; Hp1239 summary = Both Hp1036 and Hp1239 peptides exhibited potent virucidal activities against HSV-1 (EC(50) = 0.43 ± 0.09 and 0.41 ± 0.06 μM, respectively) and effective inhibitory effects when added at the viral attachment (EC(50) = 2.87 ± 0.16 and 5.73 ± 0.61 μM, respectively), entry (EC(50) = 4.29 ± 0.35 and 4.32 ± 0.47 μM, respectively) and postentry (EC(50) = 7.86 ± 0.80 and 8.41 ± 0.73 μM, respectively) steps. An extended peptide from bovine, indolicidin, showed a direct inactivation effect on cell-free HSV-1 virons by targeting viral membrane/ glycoprotein (Albiol Matanic and Castilla, 2004 Natural AMPs from scorpion venoms have attracted much attention due to their anti-viral bioactivities. To determine whether Hp1036 and Hp1239 could inhibit HSV-1 infection or replication in Vero cells, 10 lM of each peptide was added to the virus or cells at different times relative to incubation (Fig. 3A) . Various concentrations of peptides were added to Vero cells 1 h before HSV-1 infection and the inhibitory effects were determined by plaque assay. doi = 10.1016/j.antiviral.2013.11.013 id = cord-292830-gcfx1095 author = Ianevski, Aleksandr title = Novel activities of safe-in-human broad-spectrum antiviral agents date = 2018-04-23 keywords = HIV-1; ZIKV; cell; virus summary = Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. Here, we hypothesised that some of the identified safe-in-human BSAs could possess novel antiviral activities and, therefore, could be used for treatment of many different viral infections. Fig. 1 shows BSAs and other approved antiviral drugs linked to viral and host targets through viruses they inhibit. Thus, we tested several known BSA agents against (−)ssRNA, (+) ssRNA, ssRNA-RT and dsDNA viruses and identified novel activities for dalbavancin against EV1, ezetimibe against ZIKV and HIV-1, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against RVFV. We identified novel antiviral activities for dalbavancin (against EV1), ezetimibe (against HIV-1 and ZIKV), azacitidine, cyclosporine, minocycline, oritavancin and ritonavir (against RVFV) (Fig. 4) . doi = 10.1016/j.antiviral.2018.04.016 id = cord-262184-uxyb4vih author = Jockusch, Steffen title = A Library of Nucleotide Analogues Terminate RNA Synthesis Catalyzed by Polymerases of Coronaviruses that Cause SARS and COVID-19 date = 2020-06-18 keywords = Fig; SARS summary = We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. Using the criteria above, our study examines 11 nucleotide analogues with sugar or base modifications (structures shown in Fig. 1 ) for their ability to inhibit the SARS-CoV-2 or SARS-CoV RdRps: Ganciclovir 5''-triphosphate, Carbovir 5''-triphosphate, Cidofovir diphosphate, Stavudine 5''-triphosphate, Entecavir 5''-triphosphate, 2''-O-methyluridine-5''-triphosphate (2''-OMe-UTP), 3''-O-methyluridine-5''triphosphate (3''-OMe-UTP), 2''-fluoro-2''-deoxyuridine-5''-triphosphate (2''-F-dUTP), desthiobiotin-16aminoallyl-uridine-5''-triphosphate (Desthiobiotin-16-UTP), biotin-16-aminoallyl-2''-deoxyuridine-5''triphosphate (Biotin-16-dUTP) and 2''-amino-2''-deoxyuridine-5''-triphosphate (2''-NH 2 -dUTP). We then performed polymerase extension assays with the library of nucleoside triphosphate analogues (Fig. 1) either alone or in combination with natural nucleotides: 2''-OMe-UTP, 3''-OMe-UTP, 2''-F-dUTP, 2''-NH 2 -dUTP, Biotin-UTP, desthiobiotin-16-UTP, Sta-TP, Cid-DP + UTP + ATP, Car-TP + UTP + ATP + CTP, Gan-TP + UTP + ATP + CTP, or Ent-TP + UTP + ATP + CTP, following the addition of a pre-annealed RNA template and primer to a pre-assembled mixture of the SARS-CoV and/or SARS-CoV-2 RdRp (nsp12) and the two cofactor proteins (nsp7 and nsp8). doi = 10.1016/j.antiviral.2020.104857 id = cord-288146-xqxznv1r author = Kohyama, Shunsuke title = Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a date = 2009-09-11 keywords = CD8; CTL; HLA; SARS summary = title: Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a As shown in Fig. 2 , significant numbers of IFN-␥-producing CD8 + T cells (p < 0.01) were detected in mice immunized with syngeneic cells pulsed with each of nine pp1aderived peptides including pp1a-2187, -2207, -2340, -2546, -2755, -2990, -3444, -3687, and -3709 , suggesting that these nine peptides may be HLA-A*0201-restricted CTL epitopes derived from SARS-CoV pp1a protein. After HHD mice were immunized once with one of the nine liposomal peptides, spleen cells of them were prepared, stimulated with a relevant synthetic peptide, and stained for their expression of surface CD8 and intracellular IFN-␥. In summary, we have identified seven HLA-A*0201-restricted CTL epitopes derived from pp1a protein of SARS-CoV using computational algorithms, HLA-A*0201 transgenic mice and the surface-linked liposomal peptide. doi = 10.1016/j.antiviral.2009.09.004 id = cord-277443-mv7sk5aa author = Kumaki, Yohichi title = Prophylactic and therapeutic intranasal administration with an immunomodulator, Hiltonol(®) (Poly IC:LC), in a lethal SARS-CoV-infected BALB/c mouse model date = 2016-12-09 keywords = BALB; Hiltonol; IL-6; PSS; SARS summary = Hiltonol(®) at 5, 1, 0.5 or 0.25 mg/kg/day by intranasal (i.n.) route resulted in significant survival benefit when administered at selected times 24 h prior to challenge with a lethal dose of mouse-adapted severe acute respiratory syndrome coronavirus (SARS-CoV). In other studies, treatment with an interferon inducer, polyriboinosinicpolyribocytidylic acid stabilized with poly-L-lysine and carboxymethyl cellulose (poly IC:LC), given by the intranasal route, was effective in protecting mice against a lethal infection with mouseadapted SARS-CoV and reduced viral lung titers (Kumaki et al., 2010) . These treated, SARS-CoVinfected mice receiving the various Hiltonol ® dosing regimens were also significantly protected against weight loss due to virus infection (Table 1 , p < 0.05-p<0.001) from days 0e3 post virus exposure when the greatest weight loss occurred in this mouse model. doi = 10.1016/j.antiviral.2016.12.007 id = cord-266520-n439dwcx author = Levanova, Alesia A. title = Enzymatically synthesized 2''-fluoro-modified Dicer-substrate siRNA swarms against herpes simplex virus demonstrate enhanced antiviral efficacy and low cytotoxicity date = 2020-08-13 keywords = Fig; RNA; UL29 summary = The antiviral efficacy of the 2''-F-siRNA swarms and the elicited cellular innate responses did not correlate suggesting that innate immunity pathways do not significantly contribute to the observed enhanced antiviral activity of the modified siRNAs. The results support further applications of enzymatically produced siRNA molecules with incorporated adenosine nucleotides, carrying fluoro-modification on ribose C2'' position, for further antiviral studies in vitro and in vivo. We have previously generated three antiviral siRNA swarms against herpes simplex virus type 1 (HSV-1) mRNAs encoding essential viral proteins, including glycoprotein B (UL27), the infected cell protein 8 (ICP8; UL29), and ICP27 (UL54) (Romanovskaya et al., 2012; Paavilainen et al., 2016) . The siRNA swarm targeting mRNA of HSV single-stranded DNA binding protein ICP8, encoded by the UL29 gene, harbors a most pronounced antiviral effect (Paavilainen et al., 2016) and induces only minimal non-specific cellular responses (Romanovskaya et al., 2012) . doi = 10.1016/j.antiviral.2020.104916 id = cord-259480-1tqfoecc author = Li, Huixin title = Recombinant duck enteritis viruses expressing major structural proteins of the infectious bronchitis virus provide protection against infectious bronchitis in chickens date = 2016-03-02 keywords = DEV; IBV summary = To design an alternative vaccine for control of infectious bronchitis in chickens, three recombinant duck enteritis viruses (rDEVs) expressing the N, S, or S1 protein of infectious bronchitis virus (IBV) were constructed using conventional homologous recombination methods, and were designated as rDEV-N, rDEV-S, and rDEV-S1, respectively. After challenge with a homologous virulent IBV strain at 21 days post-immunization, vaccinated groups showed significant differences in the percentage of birds with clinical signs, as compared to the control group (p < 0.01), as the two covalent-vaccination groups and the rDEV-S group provided better protection than the rDEV-Nor rDEV-S1-vaccinated group. The N phosphoprotein is conserved among different IBV serotypes and can induce high titers of cross-reactive antibodies and cell-mediated immunity that protects chickens from acute infection, thus it is used as a target protein in designing vaccines against IB (Williams et al., 1992; Collisson et al., 2000; Seo et al., 1997) . Antibody responses of chickens vaccinated with recombinant duck enteritis viruses expressing the N, S or S1 gene of infectious bronchitis virus (IBV). doi = 10.1016/j.antiviral.2016.03.003 id = cord-271638-0wsyl7vk author = Li, Wenmiao title = Inhibition of herpes simplex virus by myricetin through targeting viral gD protein and cellular EGFR/PI3K/Akt pathway date = 2020-03-09 keywords = Akt; Fig; HSV; Vero; hsv-1 summary = Therefore, the natural dietary flavonoid myricetin has potential to be developed into a novel anti-HSV agent targeting both virus gD protein and cellular EGFR/PI3K/Akt pathway. As shown in Fig. 2C and E, myricetin treatment (20 μM) during adsorption significantly decreased the fluorescence of ICP5 protein on cell surface, compared to that in non-treated virus control cells, suggesting that myricetin may block virus adsorption process of HSV. As shown in Fig. 3A , in HSV-2 (MOI = 3.0) infected Vero cells, obvious syncytia with multinuclear cells were observed in non-treated virus control group (HSV-2) at 7 h p.i. However, treatment with myricetin (30, 15 μM) during 5-7 h p.i. markedly blocked syncytium formation only with a limited number of small syncytia, suggesting that myricetin may inhibit HSV-induced cell fusion. However, myricetin (2.5, 5, 10, 20 μM) treatment did not significantly influence the total expression levels of EGFR, PI3K and Akt proteins in HSV-2 infected Vero cells (Fig. 4G and H) . doi = 10.1016/j.antiviral.2020.104714 id = cord-257271-jzmwy4yi author = Lin, Jung-Chung title = Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: Structure–activity relationships date = 2008-03-31 keywords = Barr; EBV; Lin summary = Previously we showed that GL inhibits Epstein-Barr virus (EBV) infection in vitro by interfering with an early step of the EBV replication cycle (possibly attachment/penetration). In previous years, we have shown that many nucleoside analogs selectively inhibit replication of Epstein-Barr virus (EBV) in vitro (Lin et al., 1983 (Lin et al., , 1984 (Lin et al., , 1985 (Lin et al., , 1987 (Lin et al., , 1991 (Lin et al., , 1992 Lin and Machida, 1988; Mar et al., 1995; for a review see Gershburg and Pagano, 2005; Lin, 2006) . As an assay system for drug effects we used Raji cells superinfected with P3HR-1 (LS) virus, which results in reactivation of the latent EBV infection and replication of virus. To determine the dose-dependent effect of GL derivatives, Raji cells were superinfected with P3HR-1 (LS) virus in the presence of various concentrations of compounds. doi = 10.1016/j.antiviral.2008.01.160 id = cord-329959-4yecwdlo author = Lin, Min-Han title = Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes date = 2017-12-28 keywords = Fig; MERS; SARS summary = Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PL(pro)s) of MERS-CoV and SARS-CoV. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL(pro) by disulfiram, while synergistic inhibition of MERS-CoV PL(pro) by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs. For the inactivation studies, SARS-CoV PL pro (0.05 μM in 20 mM phosphate buffer, pH 6.5) was incubated with different concentrations of disulfiram and peptide substrate, and enzymatic activity was traced for 5 min. On the other hand, the results of kinetic assays, continued inactivation after the removal of disulfiram, reactivation by reductant, and the phenomenon of slow-binding inhibition suggest that disulfiram may act at the active site of SARS-CoV PL pro , forming a covalent adduct with residue Cys112. doi = 10.1016/j.antiviral.2017.12.015 id = cord-264308-y6xuxj16 author = Liu, Rui title = Mouse lung slices: An ex vivo model for the evaluation of antiviral and anti-inflammatory agents against influenza viruses date = 2015-05-26 keywords = Fig; IP-10; lung; slice; virus summary = In this study, we established an ex vivo model using mouse lung slices to evaluate both antiviral and anti-inflammatory agents against influenza virus infection. Our results suggested that mouse lung slices provide a robust, convenient and cost-efficient model for the assessment of both antiviral and anti-inflammatory agents against influenza virus infection in one assay. Our results showed that the lung slice model provides a robust, convenient and cost-economical method for the screening and evaluation of both antiviral and anti-inflammatory agents against influenza virus infection in one assay. To meet the goal of this study in the establishment of an ex vivo mouse slice model for the screening and evaluation of both antiviral and anti-inflammatory drugs against influenza infection in one assay, ensuring that the ex vivo model has similar patterns in influenza-induced cytokine and chemokine responses is critical. doi = 10.1016/j.antiviral.2015.05.008 id = cord-310469-v4p01rze author = Livonesi, Márcia Cristina title = In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus date = 2007-02-28 keywords = CARV; GROV; IFN-; OROV summary = Thus, in an effort to characterize antiviral agents that could attenuate infections caused by OROV, CARV, GMAV, GROV and TCMV, we tested the in vitro and in vivo actions of IFN-␣ on these viruses. However, treatment of CARV-, GMAV-or TCMV-infected mice with IFN-␣A did not result in an increase in survival or prolongation of the mean time to death and did not prevent virus replication in the brain of animals (Table 2 and Fig. 3, respectively) . Treatment with IFN-␣A initiated 24 h after mice infection by GROV was unable to inhibit either the death of animals or the viral replication in the brain (Table 3 and Fig. 5 , respectively). In vitro and in vivo results showed that IFN-␣ was able to prevent viral replication in a limited manner, exerting antiviral effect only when administrated early and in high doses, suggesting that OROV, CARV, GMAV, GROV and TCMV present some escape mechanism from antiviral actions of the IFN-␣. doi = 10.1016/j.antiviral.2007.01.158 id = cord-312688-12san3m7 author = Martin, Baptiste title = Filovirus proteins for antiviral drug discovery: A structure/function analysis of surface glycoproteins and virus entry date = 2016-09-14 keywords = Ebola; Marburg; RNA; virus summary = title: Filovirus proteins for antiviral drug discovery: A structure/function analysis of surface glycoproteins and virus entry After replication of the viral genome and RNA transcription, nascent viral particles are assembled in a process mediated by the matrix protein VP40, and virus budding occurs at the cell surface membrane in a process that involves hijacking the host ESCRT machinery (Hartlieb and Weissenhorn, 2006; Noda et al., 2006) . However, no direct interaction between both molecules has been demonstrated yet, and recent studies suggest that a 5 b 1 -integrin is not required for GP-mediated binding of internalization, but rather is a positive regulator of cathepsins, which play an important role in processing GP 1 into its fusion-competent form within the endosomes of infected cells (Schornberg et al., 2009) . After attachment mediated by interaction between the filovirus surface protein GP 1,2 (PDB: 3CSY) and various attachment factors, the complex is internalized and routed to the endosome, where GP 1,2 is processed to trigger fusion of viral and host membranes. doi = 10.1016/j.antiviral.2016.09.001 id = cord-291143-nkv1h3uh author = Matyushenko, Victoria title = Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses date = 2020-06-22 keywords = CD4; CD8; LAIV; RSV summary = title: Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses Surprisingly, the CD69(+)CD103(+) influenza-specific CD8 Tem responses were augmented by the addition of RSV epitopes, possibly as a result of the local microenvironment formed by the RSV-specific memory T cells differentiating to T(RM) in the lungs of mice immunized with LAIV-RSV chimeric viruses. demonstrated that a booster immunization with M2 82 RSV epitope, delivered directly to the lungs by a recombinant influenza virus expressing this epitope, generated RSV-specific lung-localized memory CD8 T cells, which were associated with reduced immunopathology following RSV challenge (Schmidt et al., 2018) . However, significant levels of CD4 Tem cells, expressing both CD69 and CD103 markers associated with tissue residence, were identified in the lungs of mice immunized with either of the LAIV-RSV vaccine candidates (Fig.3B ). doi = 10.1016/j.antiviral.2020.104864 id = cord-348401-x2q9vyf2 author = Millet, Jean K. title = Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin date = 2016-07-15 keywords = MERS; cell summary = The MERS-CoV spike protein is a main determinant of virus entry into host cells as it mediates both binding to the DPP4 (dipeptidyl peptidase 4) receptor and fusion of the viral envelope with host cell membrane (Millet and Whittaker, 2014; Raj et al., 2013) . Immunofluorescence assay of MERS-CoV-infected Huh-7, MRC-5, and Vero-81 cells in presence of increasing concentrations of griffithsin. In all conditions, cells were infected with MERS-CoV strain EMC/2012 at an m.o.i. of 10, with griffithsin (1 mg/mL) added or not at different steps during virus entry. Because we have performed our assay using high m.o.i. and a short infection time, these results show the strong inhibitory activity of griffithsin on early steps of the MERS-CoV viral cycle. To better define which stage in the virus life cycle griffithsin acts on, we performed an infection assay using authentic MERS-CoV with griffithsin present at different times during viral entry steps (Fig. 4A) . doi = 10.1016/j.antiviral.2016.07.011 id = cord-285856-0sw3wt1i author = Naesens, Lieve title = Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains date = 2009-02-05 keywords = activity; influenza; virus summary = We here report on the chemical synthesis, anti-influenza virus activity and structure-activity relationship of novel glycopeptide compounds carrying a hydrophobic side chain on an aglycoristocetin backbone ( Fig. 1) . b HPLC conditions: instrument: Waters 600 with UV230nm detection; column: Lichrospher RP-8 (4 mm × 250 mm; 10 m); injection volume: 20 l (corresponding to 2 g compound); solvents: Table 2 , several asymmetric squaric diamides derived from aglycoristocetin exerted marked activity against influenza virus, the most potent compounds being the phenylbenzyl derivative 8e [average antiviral EC 50 : 0.4 M; selectivity index (SI), defined as the ratio of MCC to EC 50 : 50]; the hexanol deriva-tive 8a (EC 50 : 1 M; SI: 14) and the naphthyl derivative 8f (EC 50 : 1.4 M; SI: 10). With regard to the antiviral mode of action, time-of-addition studies suggested that 8e blocks the viral entry process, since optimal anti-influenza virus activity was obtained when the compound was added to MDCK cells 30 min prior to or simultaneously with virus infection. doi = 10.1016/j.antiviral.2009.01.003 id = cord-316996-8yimrpaz author = Nicholls, John M. title = The use of sialidase therapy for respiratory viral infections date = 2013-04-17 keywords = DAS181; Sia; virus summary = DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is the first antiviral compound in Phase II development that functions by blocking this pathogen-host interaction, by destroying the influenza host-cell receptor, sialic acid (Sia), on the surface of respiratory epithelial cells. In this paper, we provide background information on Sia and sialidases; discuss the potential role of bacterial sialidases as antiviral agents; review the in vitro and Phase II evaluation of DAS181 for the treatment of influenza; and note evidence that the drug would also be useful against parainfluenza virus infections. Even though influenza virus has been the most well characterized of the pathogens studied, it must be noted that other viruses, including cytomegalovirus (Taylor and Cooper, 1989) , rhinovirus 87 (Blomqvist et al., 2002) , mumps Urabe AM9 (ReyesLeyva et al., 2007) and the paramyxoviruses all utilize Sia (Suzuki et al., 2001) (Paulson et al., 1979) , suggesting that sialidase treatment may potentially be useful for these infections. doi = 10.1016/j.antiviral.2013.04.012 id = cord-281385-oxohdfpu author = Noble, Christian G. title = Crystal structure of dengue virus methyltransferase without S-adenosyl-L-methionine date = 2014-09-19 keywords = RNA; SAM summary = Crystal structures of almost all available flavivirus methyltransferases contain S-adenosyl-L-methionine (SAM), the methyl donor molecule that co-purifies with the enzymes. The SAM-depleted and SAM-containing MTases exhibited comparable enzymatic activities (N-7 MTase, 2 0 -O MTase, and covalent GMP-MTase complex formation the natural product Sinefungin, showing that this is a viable approach to identify novel small molecules that bind to the same pocket. This conclusion was supported by two complementary structural and functional approaches: (i) the crystal structure unequivocally shows that absence of SAM does not affect the overall conformation of DENV MTase, including the SAM-binding pocket; (ii) depletion of SAM from the recombinant MTase did not change the activities of cap methylations and GMP-MTase complex formation. Structural and functional analysis of methylation and 5 0 -RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5 doi = 10.1016/j.antiviral.2014.09.003 id = cord-308110-cco3aq4n author = Okamoto, Mika title = The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro date = 2020-07-30 keywords = CVC; CoV-2; SARS summary = In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. Since not only the inhibition of viral replication but also the control of excessive immune activation is mandatory to save COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection. doi = 10.1016/j.antiviral.2020.104902 id = cord-286103-cgky6ar6 author = Otaki, Momoko title = Inhibition of measles virus and subacute sclerosing panencephalitis virus by RNA interference date = 2006-02-13 keywords = RNA; SSPE summary = In this study, we adopted RNA interference (RNAi) strategy and examined whether small interfering RNAs (siRNAs) can be used to inhibit replication of MeV and SSPE virus. We report here that siRNAs targeted against L mRNA of MeV, either synthetic siRNAs or those generated by pcPUR + U6i-based expression plasmids, effectively and specifically inhibited replication of both MeV and SSPE virus without exhibiting any cytotoxic effect. We report here that siRNAs targeted against L mRNA of MeV, either synthetic ones or those generated by pcPUR + U6i-based expression plasmids, effectively inhibit replication of both MeV and SSPE virus. Indeed, we demonstrated in the present study that siRNAs targeted against selected portions of L mRNA of MeV, especially MV-L2 -L4 and -L5, either synthetic siRNAs or those expressed by pcPUR + U6i-based plasmids, effectively inhibited replication of both MeV and SSPE virus (Figs. doi = 10.1016/j.antiviral.2006.01.009 id = cord-264488-989t9ld1 author = Park, Il-Hyun title = Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L date = 2014-02-06 keywords = HBV; RNA summary = In the present study, the potential antiviral activity of RNase L against hepatitis B virus (HBV) was explored utilizing the recently reported infection protocol based on human hepatoma HepG2 cells stably complemented with the virus entry factor NTCP. These results suggest that HBV replication can be regulated through interferon-mediated RNA decay pathways and that activation of these host antiviral factors may represent a novel therapeutic strategy for HBV infection. Our data indicate that ligand-mediated activation of these enzymes results in a marked inhibition of HBV replication in both infected and transfected cells. With the newly established HepG2-NTCP cell culture system, which permits HBV infection, we showed that viral gene expression and replication can be profoundly reduced by 2-5Aor poly(I:C)-mediated activation of RNase L. In HBV1.2-transfected Huh-7 cells, it was further confirmed that this type of inhibition occurred mostly through viral RNA degradation via the ribonuclease function of RNase L. doi = 10.1016/j.antiviral.2014.01.021 id = cord-284076-087oltss author = Patel, Deendayal title = Peptide-conjugated morpholino oligomers inhibit porcine reproductive and respiratory syndrome virus replication date = 2007-10-04 keywords = CRL11171; PAM; PPMO; PRRSV; RNA summary = Of 12 peptide-conjugated PMO (PPMO), four were found to be highly effective at inhibiting PRRSV replication in cell culture in a dose-dependant and sequence-specific manner. In a previous study (Zhang et al., 2006) , we tested six PPMO and found one of them (5UP1), designed to target the 5 terminal region of the PRRSV genome, to be a highly effective inhibitor of PRRSV replication in a sequence-specific and dose-dependent manner. Confirmation of the CPE observations and PRRSV yield titration was obtained by IFA on CRL11171 cells after virus inoculation and PPMO treatment (Fig. 2B ). demonstrated that PPMO generated little cytotoxicity in both CRL11171 and PAM cells, further indicating that the suppression of virus replication observed in the antiviral experiments above was due to sequence-specific effects. Treatment of cells with PPMO 5UP2 or 5HP led to suppression of PRRSV replication of all North American strains, producing virus yields not detectable (ND) in this assay. doi = 10.1016/j.antiviral.2007.09.002 id = cord-277860-vzyrcmu4 author = Pizzorno, Andrés title = In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2 date = 2020-07-15 keywords = SARS summary = In vitro evaluation of antiviral activity of single and combined repurposable drugs 1 against SARS-CoV-2 2 3 Authors: Andrés Pizzorno a , Blandine Padey a,b , Julia Dubois a , Thomas Julien a,c , Aurélien 4 Traversier a , Victoria Dulière a,c , Pauline Brun a,c , Bruno Lina a,d , Manuel Rosa-Calatrava a,c* † , 5 Olivier Terrier a* † 6 7 Author affiliations: Abstract: 27 In response to the current pandemic caused by the novel SARS-CoV-2, identifying and 28 validating effective therapeutic strategies is more than ever necessary. We evaluated the in 29 vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum 30 activities, together with drugs that are currently under evaluation in clinical trials for COVID-31 19 patients. We evaluated the in 29 vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum 30 activities, together with drugs that are currently under evaluation in clinical trials for COVID-31 19 patients. doi = 10.1016/j.antiviral.2020.104878 id = cord-312965-5hcb15xc author = Qi, Yan-fei title = In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate date = 2011-11-23 keywords = ADV; HBV summary = A structural determined heteropolytungstate, [K(4)(H(2)O)(8)Cl][K(4)(H(2)O)(4)PTi(2)W(10)O(40)]·NH(2)OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The levels of HBsAg, HBeAg and extracellular HBV DNA in the medium were measured at different time points in the control group, ADV group, and compound 1 group, respectively, as shown in Fig. 4 . The levels of HBeAg, HBsAg and extracellular HBV DNA decreased with time in HepG 2.2.15 cells, indicating that the anti-HBV activity of compound 1 is time-dependent (P < 0.01). To characterize the anti-HBV mechanism of compound 1, the amounts of intracellular viral pgRNA and DNA were measured in the control group, ADV group, and compound 1 group at different concentrations, respectively, at day 5, as shown in Fig. 5 . to the cytotoxic results, compound 1 was diluted at five non-toxic concentrations (31.2, 15.6, 7.8, 3.9 , and 1.95 lM) and the anti-SARS virus activity was checked with MTT assay. doi = 10.1016/j.antiviral.2011.11.003 id = cord-298166-045evk7g author = Röcker, Annika E. title = The molecular tweezer CLR01 inhibits Ebola and Zika virus infection date = 2018-02-08 keywords = CLR01; Fig; ZIKV; Zika summary = As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Methods describing the effect of CLR01 on pseudotyped lentiviral particles (2.3.), Ebola virus infection (2.4.), the detection of ZIKV infection by a colorimetric MTT assay (2.5.) or by cell-based ZIKV immunodetection assay (2.6.), flow cytometry (2.7.) and confocal microscopy (2.8.) as well as the RNA release assay (2.9.) and the antiviral activity of CLR01 in body fluids (2.10) can be found in the supplement. doi = 10.1016/j.antiviral.2018.02.003 id = cord-008716-38sqkh9m author = Schmidt, Alexander C title = Current research on respiratory viral infections: Third International Symposium date = 2001-06-01 keywords = H5N1; RSV; infection; influenza; respiratory; vaccine; virus summary = Renewed efforts in vaccine development against respiratory viruses began in the 1960s with the observation that infants and young children, after having recovered from respiratory tract infection with adenoviruses, shed virus from their gastrointestinal tract for an extended period of time without experiencing gastrointestinal symptoms. Earlier studies of viral pathogens in immunocompromised adults indicated that CMV, herpes simplex, influenza, parainfluenza, rhinovirus, adenovirus, enterovirus, and RSV cause lower respiratory infection (Connolly et al., 1994) . Children with RSV, adenovirus or influenza virus infections have a 30% risk of developing AOM within 2 weeks of the onset of the respiratory tract infection (Henderson et al., 1982) , and coinfection with bacteria and viruses also adversely influences the outcome of AOM. Populations at high risk for complications resulting from respiratory viral infections are now better defined and a more targeted prophylaxis is possible, be it passive prophylaxis against RSV disease with monoclonal antibody preparations or active prophylaxis with influenza-or adenovirus vaccines. doi = 10.1016/s0166-3542(01)00136-x id = cord-255902-fxlbx84w author = Shephard, Adrian title = Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus date = 2015-09-25 keywords = AMC; DCBA; PIV3 summary = In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. AMC/DCBA lozenges have also been shown to have some virucidal effects in vitro on three enveloped viruses -RSV, influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) (Oxford et al., 2005) . This study investigated the in vitro virucidal activity of AMC/ DCBA alone and in a lozenge on two other enveloped viruses that can cause sore throat and respiratory illness -PIV type 3 (PIV3) and CMV (Bisno, 2001) . Taken together, these data support the use of these lozenges as a first-line treatment for sore throat caused by viral RTIs. Further investigation into the mechanisms of action and the clinical effects of AMC/DCBA and hexylresorcinol for the control of RTIs is warranted. doi = 10.1016/j.antiviral.2015.09.012 id = cord-260735-3c33r1os author = Spisakova, Martina title = Ethacrynic and α-lipoic acids inhibit vaccinia virus late gene expression date = 2008-12-04 keywords = Luc; VACV summary = In this paper, we report an original finding that two redox-modulating agents, the ethacrynic and α-lipoic acids (EA, LA), inhibit growth of vaccinia virus (VACV) in vitro. Therefore, we have first compared the effect of different redox-modulating agents on the growth of VACV, characterized by activity of luciferase expressed by a rVACV. HeLa G cells were infected with a rVACV expressing luciferase under control of a VACV late promoter p4b (Luc L; The results indicated that all tested concentrations of ␤mercapthoethanol, dithiothreitol and l-ascorbic acid significantly increased luciferase activity expressed by rVACV (500 M concentration of these agents increased luciferase activity to 150, 140, and 120% of the mock-treated controls; p < 0.05). In contrast to EA and LA, none of these agents inhibited VACV growth in HeLa G cells characterized by activity of the reporter luciferase expressed by a rVACV. doi = 10.1016/j.antiviral.2008.11.001 id = cord-297072-f5lmstyn author = Struck, Anna-Winona title = A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2 date = 2012-01-16 keywords = ACE2; RBD; SARS summary = title: A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2 Peptide (438)YKYRYL(443) is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. The interaction of SARS-CoV with its receptor ACE2 is an attractive drug target as epitopes of the RBD on the spike protein may serve as leads for the design of effective entry inhibitors (Du et al., 2009) . This method allows the determination of the binding specificity, as Table 2 Synthetic peptide library of fourteen 6mer peptides comprising RBD-residues N435-E452 and A471-S500 of SARS-CoV spike protein. We found a hexapeptide in the receptor-binding domain (RBD) of the S protein of SARS-CoV that carries a significant portion of the binding affinity of the virus to the human cell. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein doi = 10.1016/j.antiviral.2011.12.012 id = cord-316624-bqaqhp3m author = Sui, Xiuwen title = Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus date = 2009-10-30 keywords = cell summary = Virus plaque-reduction assays, PCR and RT-PCR analysis indicated that both drugs inhibited cell infection by PrV. Briefly, FITC-conjugated Annexin V (50 l/well) and propidium iodide, PI (50 l/well) were added the cells infected by drug-treated viruses, or the virus-infected cells treated with LiCl in 24-well plates and incubated at room temperature for 15 min in the dark prior to fluorescence observation. At the maximum non-toxic concentration of the drugs, the inhibition rate of LiCl and DG for PrV infection in cell culture reached 100% (Fig. 4) . The effect of both drugs on PrV-infected cells was analyzed using plaque-reduction assays. As shown in Fig. 9 , the maximum nontoxic concentration of drugs had an inhibitory activity against PrV-induced cell apoptosis. It is possible that the observed anti-apoptotic effect of DG and LiCl during PRV infection is indirect and due to the reduced virus replication caused by the drugs. doi = 10.1016/j.antiviral.2009.10.014 id = cord-336093-ic6q6ke8 author = Sun, Ying title = Yeast-based assays for the high-throughput screening of inhibitors of coronavirus RNA cap guanine-N7-methyltransferase date = 2014-02-11 keywords = Fig; RNA; SARS; yeast summary = Abbreviations: SARS, severe acute respiratory syndrome; SARS-CoV, SARS coronavirus; nsp, nonstructural protein; N7-MTase, guanine-N7-methyltransferase; 2 0 -O-MTase, 2 0 -O-methyltransferase; AdoMet, S-adenosyl-L-methionine; AdoHcy, S-adenosyl-L-homocysteine; ATA, aurintricarboxylic acid; IC 50 , inhibitory concentration at 50% activity. A single transformed colony of the YBS40 strain containing plasmids expressing human N7-MTase (MT-Human), SARS-CoV N7-MTase (MT-SARS), N7-MTases of other coronaviruses (MT-MHV, MT-TGEV, and MT-IBV), and the pMceK294A vector as control (representing the yeast N7-MTase [MT-Yeast]), were inoculated separately into 5 ml of a basic medium (Min SD Base) lacking tryptophan and incubated at 30°C for 21-24 h until reaching a similar final cell density in the stationary phase (0.5-1.0 Â 10 8 cells/ml) (Chrebet et al., 2005) . Although AdoHcy, ATA and sinefungin, were previously reported to be inhibitors of coronavirus RNA MTases in vitro , only sinefungin significantly suppressed the growth of the MT-yeast, MT-human, and MT-SARS yeast cells (Fig. 3 ). doi = 10.1016/j.antiviral.2014.02.002 id = cord-256280-ihj102hi author = Takano, Tomomi title = The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection date = 2017-08-03 keywords = FCoV; U18666A summary = title: The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection In this study, we investigated whether U18666A, the cholesterol synthesis and transport inhibitor, shows antiviral effects against type I FCoV. U18666A induced cholesterol accumulation in cells and inhibited type I FCoV replication. These findings suggest that cell membrane cholesterol plays an important role in type I FCoV infection. In order to confirm the effects of the accumulation of cholesterol on FCoV infection, fcwf-4 cells were pretreated with U18666A, followed by virus inoculation. When cells were pretreated with cholesterol biosynthesis inhibitors, only itraconazole significantly inhibited FCoV-I KU2 plaque formation. In addition, treatment of cells with U18666A did not influence the cellular cholesterol level, suggesting that U18666A inhibits type I FCoV replication at a concentration suppressing cholesterol transporter but not influencing the synthesis system. It was suggested that U18666A inhibits type I FCoV replication by suppressing the intracellular cholesterol transporter. doi = 10.1016/j.antiviral.2017.07.022 id = cord-329642-5t8yuq4v author = Takano, Tomomi title = Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo date = 2013-05-03 keywords = FIPV; Post; chloroquine summary = Several agents that significantly inhibit FCoV replication in vitro have been identified (Balzarini et al., 2006; Barlough and Shacklett, 1994; Hsieh et al., 2010; Kim et al., 2012; Takano et al., 2008) ; however, whether or not these agents exhibit a therapeutic effect in cats with FIP has not been investigated. The effect of chloroquine on FIPV infection in fcwf-4 cells and SPF cat-derived monocytes was investigated. In monocytes inoculated with a mixture of FIPV and MAb 6-4-2, IL-1b, TNF-a and IL-6 mRNA expression levels were significantly lower in the Pre/Post treatment group than in the None group (Fig. 3B) . The influence of chloroquine on cytokine mRNA and FCoV N gene expressions was investigated in monocytes from cats with FIP. IL-1b, TNF-a, and IL-6 mRNA expression levels of PBMC in FIPV-infected cats treated with chloroquine. In this study, chloroquine significantly inhibited inflammatory cytokine mRNA expression levels in FIPV-infected monocytes. doi = 10.1016/j.antiviral.2013.04.016 id = cord-283739-p7b4mtbl author = Theerawatanasirikul, Sirin title = Structural-based virtual screening and in vitro assays for small molecules inhibiting the feline coronavirus 3CL protease as a surrogate platform for coronaviruses date = 2020-09-07 keywords = 3CL; FIPV summary = We investigated the potential drug-liked compounds and their inhibitory interaction on the 3CL(pro) active sites of CoVs by the structural-bases virtual screening. Evaluation of antiviral activity using cell-based assay showed that NSC629301 and NSC71097 could strongly inhibit the cytopathic effect and also reduced replication of FIPV in CRFK cells in all examined conditions with the low range of EC(50) (6.11 ± 1.90 to 7.75 ± 0.48 μM and 1.99 ± 0.30 to 4.03 ± 0.60 μM, respectively), less than those of ribavirin and lopinavir. According to the FIPV 3CL pro structurral based study, we determined if the candidate 293 compounds that could bind to the active site and inhibited the protease activity still actively 294 Cys144 and His41, the active residues of FIPV 3CL pro , formed the π-alkyl interaction 352 and hydrogen bond to the compounds, respectively. doi = 10.1016/j.antiviral.2020.104927 id = cord-270498-hh6h50t2 author = Tseng, Chin-Kai title = Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date = 2017-09-19 keywords = HCV; HO-1; IFN; Nrf2 summary = Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. In this study, our data revealed that celastrol significantly inhibits HCV replication, and that the anti-HCV effect of celastrol was attenuated by the HO-1 specific inhibitor tin mesoporphyrin (SnMP) or HO-1 gene expression silencing. Celastrol-mediated HO-1 induction contributed to the anti-HCV action through inducing antiviral IFN response and inhibiting HCV NS3 protease activity. As shown in Fig. 7B , HO-1 RNA expression levels were induced by celastrol compared with non-celastrol treated cells and the JNK inhibitor SP600125 significantly reduced the HO-1 inductive effect of celastrol. In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs. doi = 10.1016/j.antiviral.2017.09.010 id = cord-285505-8norumv6 author = Vere Hodge, R. Anthony title = Meeting report: 27th International conference on antiviral research, in Raleigh, NC, USA date = 2014-09-16 keywords = HBV; HCV; HIV; RNA; TDF; USA; dna summary = The focus of John''s presentation was on the research conducted in his own and his collaborators'' laboratories that ultimately led to the invention of three compounds which were discovered to have antiviral activity against human cytomegalovirus (HCMV) and which later entered clinical trials: BDCRB pyranoside (GW275175X) (Phase I), maribavir (Phases I, II and III) and cyclopropavir (Phase I). In monotherapy studies after oral dosing with TDF (300 mg) and TAF (25 mg), the plasma TFV AUC is reduced from 1920 to 268 ng.h/ml respectively whereas the reduction in HIV load from baseline is improved, from log 10 0.97 to log 10 1.46 copies/ml, respectively, reflecting the more efficient delivery of TAF to target cells and tissues. David Margolis, University of North Carolina, NC, USA In HIV-infected patients, there is a long-lasting reservoir of HIV in the form of integrated viral DNA in resting CD4+ memory cells of the host immune system. doi = 10.1016/j.antiviral.2014.08.009 id = cord-316503-wtmmewiz author = Warren, Travis K. title = Advanced morpholino oligomers: A novel approach to antiviral therapy date = 2012-02-14 keywords = MARV; RNA summary = Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense oligonucleotide analogs that are designed to interfere with translational processes by forming base-pair duplexes with specific RNA sequences. Peptide conjugated PMOs (PPMOs; Fig. 2 ), which include positively charged amino acid residues such as arginine, have been viewed as particularly promising transporters and have shown efficacy in multiple in vivo models of viral infection (Enterlein et al., 2006; Paessler et al., 2008; Stein, 2008; Swenson et al., 2009) . While PPMOs are efficacious in multiple in vivo models of viral infections, PPMOs are more poorly tolerated in vivo compared to neutral-charge PMOs. In mice, dose-dependent reductions in weight, behavioral alterations, and mild liver histopathology were observed following repeat administration of 200-300 lg doses of a PMO conjugated to an arginine-rich peptide (Deas et al., 2007) . doi = 10.1016/j.antiviral.2012.02.004 id = cord-295421-zy517zwr author = Xu, Jinfang title = Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo date = 2014-06-26 keywords = BHK; FMDV; IFITM3 summary = title: Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo Ectopic expression of sIFITM3 significantly inhibited non-enveloped foot-and-mouth disease virus (FMDV) infection in BHK-21 cells. Furthermore, sIFITM3 blocked FMDV infection at early steps in the virus life cycle by disrupting viral attachment to the host cell surface. Ectopic expression of sIFITM3 inhibited infection of non-enveloped FMDV in baby hamster kidney (BHK-21) cells by disrupting viral attachment, and this differs from human IFITM3 restriction on enveloped viruses. Two days post infection of the cell lines with viruses, plaque assay showed that BHK-sIFITM3 was less susceptible to infection by type O FMDV strains O/ES/ 2001, O/GD/2010, and O/AH/2010 than the control BHK-eGFP, and reduced plaque formation numbers by over 11-to 24-fold (Fig. 2C ). In addition, post infection with type Asia 1 FMDV Asia 1/JS/2005, the plaque formation number was reduced to over 13fold in BHK-sIFITM3 cells (Fig. 2C) . doi = 10.1016/j.antiviral.2014.06.008 id = cord-299964-sn5o3ugb author = Xue, Qiao title = Seneca Valley Virus 3C protease negatively regulates the type I interferon pathway by acting as a viral deubiquitinase date = 2018-11-05 keywords = SVV; TBK1; rig summary = Furthermore, 3C(pro) inhibited the ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), and TNF receptor-associated factor 3 (TRAF3), thereby blocking the expression of interferon (IFN)-β and IFN stimulated gene 54 (ISG54) mRNAs. A detailed analysis revealed that mutations (H48A, C160A, or H48A/C160A) that ablate the Cys and His residues of 3C(pro) abrogated its deubiquitinating activity and the ability of 3C(pro) to block IFN-β induction. To determine whether SVV can evade innate immune response by inhibiting the host ubiquitination, HEK293T cells were transfected with FLAG-tagged VP1, VP2, 2AB, 2B, 2C, 3D, 3C plasmids along with HA-Ub plasmid. As shown in Fig. 1A , expression of 3C pro resulted in a dose-dependent reduction of the level of ubiquitinated cellular proteins compared with that in the empty vector-transfected cells. Taken together, these results indicate that SVV and 3C pro inhibit the ubiquitination of RIG-I, TBK1, and TRAF3 in a DUB-dependent manner. doi = 10.1016/j.antiviral.2018.10.028 id = cord-337645-t6py0oyw author = Yin, Jiechao title = Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus date = 2010-10-14 keywords = TGEV summary = Though S protein was not solubilized by cold non-ionic detergents, this behavior was unchanged when cholesterol was depleted from viral membrane by methyl-β-cyclodextrin (MβCD) and the protein did not comigrate with cellular DRM marker proteins in flotation analyses. A functional analysis suggests that cholesterol depletion affects a post-adsorption step in the virus entry process that requires membrane rearrangements. As cholesterol depletion from TGE virions results in a reduction of viral infectivity (Ren et al., 2008) , we were interested to find out whether the surface protein S that mediates virus entry is localized in DRMs. For this purpose, we analyzed whether the TGEV S protein is resistant to solubilization by Triton X-100 at 4 • C. This result indicates that the surface protein of TGEV is arranged in the viral envelope in a detergent-resistant way that is not affected by cholesterol depletion. doi = 10.1016/j.antiviral.2010.10.002 id = cord-263042-qdmunb9l author = Zhao, Yongkun title = Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model date = 2016-11-24 keywords = East; MERS; RBD summary = Passive transfer of equine immune antibodies significantly reduced virus titers and accelerated virus clearance from the lungs of MERS-CoV infected mice. Our data show that horses immunized with MERS-CoV VLPs can serve as a primary source of protective F(ab'')(2) for potential use in the prophylactic or therapeutic treatment of exposed or infected patients. Several research groups have developed and produced anti-MERS patientderived or humanized monoclonal neutralizing antibodies in vitro that were able to protect MERS-CoV infected mice (Corti et al., 2015; Li et al., 2015; Zhao et al., 2014) . Prophylactic or therapeutic treatment of MERS-CoV infected mice with either IgG or F(ab'') 2 significantly decreased the virus load in their lungs. In both prophylactic and therapeutic settings, passive transfer of equine immune antibodies resulted in a 2e4 log reduction of virus titers in the lungs of MERS-CoV infected mice, and accelerated virus clearance in the serum treated group (Fig. 5A, B) . doi = 10.1016/j.antiviral.2016.11.016 id = cord-260071-z29b30sd author = Zhong, Yu title = Highly potent anti-HIV-1 activity isolated from fermented Polygonum tinctorium Aiton date = 2005-03-27 keywords = HIV-1; MT-4; Sukumo; extract summary = All of these compounds are assumed to exert their anti-HIV activity by shielding the positively charged sites in the V3 loop region of the viral gp120 envelope glycoprotein, and interrupting virus attachment to the negatively charged heparan sulfate proteoglycans on cell surface, and inhibiting the specific binding to the CD4 receptor of CD4 + cells. PHA (1 g/ml, Sigma-Aldrich)/IL-2 (100 U/ml, Shionogi, Osaka, Japan) activated PBMCs were infected for 2 h with 20 ng of HIV-1 p24 Gag (X4/NL4-3 or R5/JRCSF) in the presence or absence of the Sukumo extract (0.64-400 g/ml), washed three times with PBS and cultured for 7 days in RPMI-1640 medium/10% FBS plus 100 U/ml IL-2 with or without the Sukumo extract. Sukumo extract was also evaluated for the inhibition of wild-type herpes simplex virus-1 replication in infected Vero cells, using a standard viral plaque assay (Fig. 1B) . doi = 10.1016/j.antiviral.2005.02.003 id = cord-299224-7jgmxtzd author = Zhu, Qingyuan title = A synthetic STING agonist inhibits the replication of Human Parainfluenza Virus 3 and Rhinovirus 16 through distinct mechanisms date = 2020-09-17 keywords = Fig; HRV16; sting summary = In this study, using dimeric amidobenzimidazole (diABZI), a newly discovered synthetic small molecule STING receptor agonist with much higher potency than CDNs, we found that activation of STING elicits potent antiviral effects against parainfluenza virus type 3 (PIV3) and human rhinovirus 16 (HRV16), two representative respiratory viral pathogens. In both PIV3-infected Hep2 and H1-HeLa cells, BX795 completely abolished the anti-PIV3 activity of diABZI, whereas no significant impairment was observed with CQ treatment, J o u r n a l P r e -p r o o f suggesting that the activation of immune responses via TBK1 plays a dominant role in STING-mediated anti-PIV3 activity (Figs. In this study, the diABZI STING agonist demonstrated potent antiviral activity against multiple respiratory RNA viruses, represented by PIV3 and HRV16, which broadly affect human health and have no effective treatment or vaccine. doi = 10.1016/j.antiviral.2020.104933 id = cord-299189-59d4aojh author = Zou, Hao title = Transmissible gastroenteritis virus: Identification of M protein-binding peptide ligands with antiviral and diagnostic potential date = 2013-07-02 keywords = ELISA; TGEV summary = title: Transmissible gastroenteritis virus: Identification of M protein-binding peptide ligands with antiviral and diagnostic potential In this study, the M protein of transmissible gastroenteritis virus (TGEV) was used to biopan a 12-mer phage display random peptide library. Plaque-reduction assays revealed that pepTGEV-M7 was able to prevent TGEV infection in vitro (p < 0.01) following pretreatment of the virus with the peptide. coli (Fig. 1) for use in biopanning the phage display library to identify peptides that bind the M protein of TGEV. Ten different TGEV-M protein-reactive phages were identified by ELISA, when rTGEV-M was used as the coating antigen (Fig. 2a) . 100TCID50 TGEV virus was pre-incubated with 2-fold, serially-diluted (500-31.25 lg/ml) peptide (pepTGEV-M7) then added to ST cells for 48 h. Bacterial expression of antigenic sites A and D in the spike protein of transmissible gastroenteritis virus and evaluation of their inhibitory effects on viral infection doi = 10.1016/j.antiviral.2013.06.015 id = cord-020010-q58x6xb0 author = nan title = 19th ICAR Abstracts: date = 2006-03-13 keywords = CDV; Department; HCMV; HCV; HIV; HIV-1; Institute; REP; RNA; Research; ST-246; Sciences; USA; University; Virology; WNV; activity; antiviral; cell; compound; dna; infection; virus summary = In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. doi = 10.1016/j.antiviral.2006.02.001 id = cord-023608-w2g7v7g1 author = nan title = ISAR News date = 2017-10-20 keywords = ICAR; ISAR; RNA; Society; dengue; virus summary = ICAR retains its flavor and personality, providing an interdisciplinary forum at which investigators involved in basic, translational, and clinical research worldwide meet to review recent developments in all areas of antiviral research, drug and vaccine development. Additionally, satellite activities such as the Women in Science Roundtable, the Career Development Panel and the New Member and First Time Attendee luncheon (The Happy Hour) provided an opportunity to discuss other issues of relevance. With so many different competing conferences and meetings to attend and a long economic crisis of which scientific research did not escape, ISAR has gone through great financial efforts to continue supporting the participation of students, postdocs and young investigators. The TCFF Awards support the professional development of women with potential to make significant contributions to the field of Antiviral Research by providing funds to attend a conference, visit another laboratory, take a course, or acquire specialized training. doi = 10.1016/s0166-3542(17)30664-2 id = cord-332952-d5l60cgc author = nan title = MERS: Progress on the global response, remaining challenges and the way forward date = 2018-09-17 keywords = East; MERS; Middle summary = Typical of an emerging zoonosis, Middle East respiratory syndrome coronavirus (MERS-CoV) has an animal reservoir, i.e. dromedary camels in which the virus causes little to no disease (Mohd et al., 2016) . For example, studies of respiratory pathogens (Yu et al., 2007; Tran et al., 2012; Thompson et al., 2013) and MERS-CoV conducted in the Middle East (Assiri et al., 2013; Oboho et al., 2015; Hunter et al., 2016; Balkhy et al., 2016) and the Republic of Korea (Bin et al., 2016; Kim et al., 2016a Kim et al., , 2016b Nam et al., 2017) illustrate that aerosol-generating procedures and non-invasive ventilation, combined with inappropriate infection prevention and control practices and lack of adherence to standard practices had an important role in facilitating human-to-human transmission in health care settings. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study Sero-prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia doi = 10.1016/j.antiviral.2018.09.002