Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase
Identifieur interne : 000B75 ( Main/Exploration ); précédent : 000B74; suivant : 000B76Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase
Auteurs : Ariane J. Brown [États-Unis] ; John J. Won [États-Unis] ; Rachel L. Graham [États-Unis] ; Kenneth H. Dinnon [États-Unis] ; Amy C. Sims [États-Unis] ; Joy Y. Feng [États-Unis] ; Tomas Cihlar [États-Unis] ; Mark R. Denison [États-Unis] ; Ralph S. Baric [États-Unis] ; Timothy P. Sheahan [États-Unis]Source :
- Antiviral Research [ 0166-3542 ] ; 2019.
Abstract
The genetically diverse
Url:
DOI: 10.1016/j.antiviral.2019.104541
PubMed: 31233808
PubMed Central: 6699884
Affiliations:
- États-Unis
- Californie, Caroline du Nord, Tennessee
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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Brown</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Won, John J" sort="Won, John J" uniqKey="Won J" first="John J." last="Won">John J. Won</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H." last="Dinnon">Kenneth H. Dinnon</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name><affiliation wicri:level="2"><nlm:aff id="aff2">Gilead Sciences, Inc., Foster City, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gilead Sciences, Inc., Foster City, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation wicri:level="2"><nlm:aff id="aff2">Gilead Sciences, Inc., Foster City, CA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Gilead Sciences, Inc., Foster City, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><affiliation wicri:level="2"><nlm:aff id="aff3">Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P." last="Sheahan">Timothy P. Sheahan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The genetically diverse <italic>Orthocoronavirinae</italic> (CoV) family is prone to cross species transmission and disease emergence in both humans and livestock. Viruses similar to known epidemic strains circulating in wild and domestic animals further increase the probability of emergence in the future. Currently, there are no approved therapeutics for any human CoV presenting a clear unmet medical need. Remdesivir (RDV, GS-5734) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of RNA virus families including <italic>Filoviridae</italic>, <italic>Paramyxoviridae</italic>, <italic>Pneumoviridae</italic>, and <italic>Orthocoronavirinae</italic>, through the targeting of the viral RNA dependent RNA polymerase (RdRp). We developed multiple assays to further define the breadth of RDV antiviral activity against the CoV family. Here, we show potent antiviral activity of RDV against endemic human CoVs OC43 (HCoV-OC43) and 229E (HCoV-229E) with submicromolar EC<sub>50</sub> values. Of known CoVs, the members of the <italic>deltacoronavirus</italic> genus have the most divergent RdRp as compared to SARS- and MERS-CoV and both avian and porcine members harbor a native residue in the RdRp that confers resistance in beta-CoVs. Nevertheless, RDV is highly efficacious against porcine deltacoronavirus (PDCoV). These data further extend the known breadth and antiviral activity of RDV to include both contemporary human and highly divergent zoonotic CoV and potentially enhance our ability to fight future emerging CoV.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Agostini, M L" uniqKey="Agostini M">M.L. Agostini</name></author><author><name sortKey="Andres, E L" uniqKey="Andres E">E.L. Andres</name></author><author><name sortKey="Sims, A C" uniqKey="Sims A">A.C. Sims</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. 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Brown</name></region><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R." last="Denison">Mark R. Denison</name><name sortKey="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H." last="Dinnon">Kenneth H. Dinnon</name><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P." last="Sheahan">Timothy P. Sheahan</name><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name><name sortKey="Won, John J" sort="Won, John J" uniqKey="Won J" first="John J." last="Won">John J. Won</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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