An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.
Identifieur interne : 000305 ( PubMed/Checkpoint ); précédent : 000304; suivant : 000306An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.
Auteurs : Timothy P. Sheahan [États-Unis] ; Amy C. Sims [États-Unis] ; Shuntai Zhou [États-Unis] ; Rachel L. Graham [États-Unis] ; Andrea J. Pruijssers [États-Unis] ; Maria L. Agostini [États-Unis] ; Sarah R. Leist [États-Unis] ; Alexandra Sch Fer [États-Unis] ; Kenneth H. Dinnon [États-Unis] ; Laura J. Stevens [États-Unis] ; James D. Chappell [États-Unis] ; Xiaotao Lu [États-Unis] ; Tia M. Hughes [États-Unis] ; Amelia S. George [États-Unis] ; Collin S. Hill [États-Unis] ; Stephanie A. Montgomery [États-Unis] ; Ariane J. Brown [États-Unis] ; Gregory R. Bluemling [États-Unis] ; Michael G. Natchus [États-Unis] ; Manohar Saindane [États-Unis] ; Alexander A. Kolykhalov [États-Unis] ; George Painter [États-Unis] ; Jennifer Harcourt ; Azaibi Tamin ; Natalie J. Thornburg ; Ronald Swanstrom [États-Unis] ; Mark R. Denison [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Science translational medicine [ 1946-6242 ] ; 2020.
Abstract
Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N4-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.
DOI: 10.1126/scitranslmed.abb5883
PubMed: 32253226
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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<author><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name>
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<author><name sortKey="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H" last="Dinnon">Kenneth H. Dinnon</name>
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<author><name sortKey="Stevens, Laura J" sort="Stevens, Laura J" uniqKey="Stevens L" first="Laura J" last="Stevens">Laura J. Stevens</name>
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<author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</name>
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<author><name sortKey="Hughes, Tia M" sort="Hughes, Tia M" uniqKey="Hughes T" first="Tia M" last="Hughes">Tia M. Hughes</name>
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<author><name sortKey="Brown, Ariane J" sort="Brown, Ariane J" uniqKey="Brown A" first="Ariane J" last="Brown">Ariane J. Brown</name>
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<author><name sortKey="Natchus, Michael G" sort="Natchus, Michael G" uniqKey="Natchus M" first="Michael G" last="Natchus">Michael G. Natchus</name>
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<author><name sortKey="Saindane, Manohar" sort="Saindane, Manohar" uniqKey="Saindane M" first="Manohar" last="Saindane">Manohar Saindane</name>
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<author><name sortKey="Kolykhalov, Alexander A" sort="Kolykhalov, Alexander A" uniqKey="Kolykhalov A" first="Alexander A" last="Kolykhalov">Alexander A. Kolykhalov</name>
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<author><name sortKey="Painter, George" sort="Painter, George" uniqKey="Painter G" first="George" last="Painter">George Painter</name>
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<author><name sortKey="Harcourt, Jennifer" sort="Harcourt, Jennifer" uniqKey="Harcourt J" first="Jennifer" last="Harcourt">Jennifer Harcourt</name>
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<author><name sortKey="Tamin, Azaibi" sort="Tamin, Azaibi" uniqKey="Tamin A" first="Azaibi" last="Tamin">Azaibi Tamin</name>
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<author><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J" last="Thornburg">Natalie J. Thornburg</name>
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<author><name sortKey="Swanstrom, Ronald" sort="Swanstrom, Ronald" uniqKey="Swanstrom R" first="Ronald" last="Swanstrom">Ronald Swanstrom</name>
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<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
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<author><name sortKey="Zhou, Shuntai" sort="Zhou, Shuntai" uniqKey="Zhou S" first="Shuntai" last="Zhou">Shuntai Zhou</name>
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<author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L" last="Graham">Rachel L. Graham</name>
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<author><name sortKey="Pruijssers, Andrea J" sort="Pruijssers, Andrea J" uniqKey="Pruijssers A" first="Andrea J" last="Pruijssers">Andrea J. Pruijssers</name>
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<author><name sortKey="Agostini, Maria L" sort="Agostini, Maria L" uniqKey="Agostini M" first="Maria L" last="Agostini">Maria L. Agostini</name>
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</author>
<author><name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R" last="Leist">Sarah R. Leist</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stevens, Laura J" sort="Stevens, Laura J" uniqKey="Stevens L" first="Laura J" last="Stevens">Laura J. Stevens</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lu, Xiaotao" sort="Lu, Xiaotao" uniqKey="Lu X" first="Xiaotao" last="Lu">Xiaotao Lu</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hughes, Tia M" sort="Hughes, Tia M" uniqKey="Hughes T" first="Tia M" last="Hughes">Tia M. Hughes</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="George, Amelia S" sort="George, Amelia S" uniqKey="George A" first="Amelia S" last="George">Amelia S. George</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hill, Collin S" sort="Hill, Collin S" uniqKey="Hill C" first="Collin S" last="Hill">Collin S. Hill</name>
<affiliation wicri:level="4"><nlm:affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Montgomery, Stephanie A" sort="Montgomery, Stephanie A" uniqKey="Montgomery S" first="Stephanie A" last="Montgomery">Stephanie A. Montgomery</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599</wicri:regionArea>
<wicri:noRegion>27599</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Brown, Ariane J" sort="Brown, Ariane J" uniqKey="Brown A" first="Ariane J" last="Brown">Ariane J. Brown</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bluemling, Gregory R" sort="Bluemling, Gregory R" uniqKey="Bluemling G" first="Gregory R" last="Bluemling">Gregory R. Bluemling</name>
<affiliation wicri:level="1"><nlm:affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322</wicri:regionArea>
<wicri:noRegion>30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Natchus, Michael G" sort="Natchus, Michael G" uniqKey="Natchus M" first="Michael G" last="Natchus">Michael G. Natchus</name>
<affiliation wicri:level="1"><nlm:affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322</wicri:regionArea>
<wicri:noRegion>30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Saindane, Manohar" sort="Saindane, Manohar" uniqKey="Saindane M" first="Manohar" last="Saindane">Manohar Saindane</name>
<affiliation wicri:level="1"><nlm:affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322</wicri:regionArea>
<wicri:noRegion>30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kolykhalov, Alexander A" sort="Kolykhalov, Alexander A" uniqKey="Kolykhalov A" first="Alexander A" last="Kolykhalov">Alexander A. Kolykhalov</name>
<affiliation wicri:level="1"><nlm:affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322</wicri:regionArea>
<wicri:noRegion>30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Painter, George" sort="Painter, George" uniqKey="Painter G" first="George" last="Painter">George Painter</name>
<affiliation wicri:level="1"><nlm:affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322</wicri:regionArea>
<wicri:noRegion>30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Harcourt, Jennifer" sort="Harcourt, Jennifer" uniqKey="Harcourt J" first="Jennifer" last="Harcourt">Jennifer Harcourt</name>
<affiliation><nlm:affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</nlm:affiliation>
<wicri:noCountry code="subField">Division of Viral Diseases Atlanta GA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Tamin, Azaibi" sort="Tamin, Azaibi" uniqKey="Tamin A" first="Azaibi" last="Tamin">Azaibi Tamin</name>
<affiliation><nlm:affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</nlm:affiliation>
<wicri:noCountry code="subField">Division of Viral Diseases Atlanta GA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J" last="Thornburg">Natalie J. Thornburg</name>
<affiliation><nlm:affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</nlm:affiliation>
<wicri:noCountry code="subField">Division of Viral Diseases Atlanta GA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Swanstrom, Ronald" sort="Swanstrom, Ronald" uniqKey="Swanstrom R" first="Ronald" last="Swanstrom">Ronald Swanstrom</name>
<affiliation wicri:level="4"><nlm:affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</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="1"><nlm:affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232</wicri:regionArea>
<wicri:noRegion>37232</wicri:noRegion>
</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:affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. sheahan@email.unc.edu rbaric@email.unc.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Science translational medicine</title>
<idno type="eISSN">1946-6242</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
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<front><div type="abstract" xml:lang="en">Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N<sup>4</sup>
-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N<sup>4</sup>
-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32253226</PMID>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>17</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1946-6242</ISSN>
<JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year>
<Month>Apr</Month>
<Day>06</Day>
</PubDate>
</JournalIssue>
<Title>Science translational medicine</Title>
<ISOAbbreviation>Sci Transl Med</ISOAbbreviation>
</Journal>
<ArticleTitle>An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">eabb5883</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/scitranslmed.abb5883</ELocationID>
<Abstract><AbstractText>Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N<sup>4</sup>
-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N<sup>4</sup>
-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.</AbstractText>
<CopyrightInformation>Copyright © 2020, American Association for the Advancement of Science.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Sheahan</LastName>
<ForeName>Timothy P</ForeName>
<Initials>TP</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. sheahan@email.unc.edu rbaric@email.unc.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Sims</LastName>
<ForeName>Amy C</ForeName>
<Initials>AC</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Shuntai</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Graham</LastName>
<ForeName>Rachel L</ForeName>
<Initials>RL</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pruijssers</LastName>
<ForeName>Andrea J</ForeName>
<Initials>AJ</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Agostini</LastName>
<ForeName>Maria L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leist</LastName>
<ForeName>Sarah R</ForeName>
<Initials>SR</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schäfer</LastName>
<ForeName>Alexandra</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dinnon</LastName>
<ForeName>Kenneth H</ForeName>
<Initials>KH</Initials>
<Suffix>3rd</Suffix>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stevens</LastName>
<ForeName>Laura J</ForeName>
<Initials>LJ</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chappell</LastName>
<ForeName>James D</ForeName>
<Initials>JD</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lu</LastName>
<ForeName>Xiaotao</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hughes</LastName>
<ForeName>Tia M</ForeName>
<Initials>TM</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>George</LastName>
<ForeName>Amelia S</ForeName>
<Initials>AS</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hill</LastName>
<ForeName>Collin S</ForeName>
<Initials>CS</Initials>
<AffiliationInfo><Affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Montgomery</LastName>
<ForeName>Stephanie A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brown</LastName>
<ForeName>Ariane J</ForeName>
<Initials>AJ</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bluemling</LastName>
<ForeName>Gregory R</ForeName>
<Initials>GR</Initials>
<AffiliationInfo><Affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Natchus</LastName>
<ForeName>Michael G</ForeName>
<Initials>MG</Initials>
<AffiliationInfo><Affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Saindane</LastName>
<ForeName>Manohar</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kolykhalov</LastName>
<ForeName>Alexander A</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Painter</LastName>
<ForeName>George</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA, 30322, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Harcourt</LastName>
<ForeName>Jennifer</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tamin</LastName>
<ForeName>Azaibi</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Thornburg</LastName>
<ForeName>Natalie J</ForeName>
<Initials>NJ</Initials>
<AffiliationInfo><Affiliation>Centers for Disease Control and Prevention, Division of Viral Diseases Atlanta GA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Swanstrom</LastName>
<ForeName>Ronald</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Denison</LastName>
<ForeName>Mark R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, TN, 37232,USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baric</LastName>
<ForeName>Ralph S</ForeName>
<Initials>RS</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. sheahan@email.unc.edu rbaric@email.unc.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 AI108197</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
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<Grant><GrantID>R01 AI132178</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U19 AI109680</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U19 AI142759</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>04</Month>
<Day>06</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Sci Transl Med</MedlineTA>
<NlmUniqueID>101505086</NlmUniqueID>
<ISSNLinking>1946-6234</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>03</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>04</Month>
<Day>02</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>4</Month>
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<PubMedPubDate PubStatus="medline"><Year>2020</Year>
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<ArticleId IdType="doi">10.1126/scitranslmed.abb5883</ArticleId>
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<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
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<settlement><li>Chapel Hill (Caroline du Nord)</li>
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<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
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<country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P" last="Sheahan">Timothy P. Sheahan</name>
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<name sortKey="Chappell, James D" sort="Chappell, James D" uniqKey="Chappell J" first="James D" last="Chappell">James D. Chappell</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="George, Amelia S" sort="George, Amelia S" uniqKey="George A" first="Amelia S" last="George">Amelia S. George</name>
<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L" last="Graham">Rachel L. Graham</name>
<name sortKey="Hill, Collin S" sort="Hill, Collin S" uniqKey="Hill C" first="Collin S" last="Hill">Collin S. Hill</name>
<name sortKey="Hughes, Tia M" sort="Hughes, Tia M" uniqKey="Hughes T" first="Tia M" last="Hughes">Tia M. Hughes</name>
<name sortKey="Kolykhalov, Alexander A" sort="Kolykhalov, Alexander A" uniqKey="Kolykhalov A" first="Alexander A" last="Kolykhalov">Alexander A. Kolykhalov</name>
<name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R" last="Leist">Sarah R. Leist</name>
<name sortKey="Lu, Xiaotao" sort="Lu, Xiaotao" uniqKey="Lu X" first="Xiaotao" last="Lu">Xiaotao Lu</name>
<name sortKey="Montgomery, Stephanie A" sort="Montgomery, Stephanie A" uniqKey="Montgomery S" first="Stephanie A" last="Montgomery">Stephanie A. Montgomery</name>
<name sortKey="Natchus, Michael G" sort="Natchus, Michael G" uniqKey="Natchus M" first="Michael G" last="Natchus">Michael G. Natchus</name>
<name sortKey="Painter, George" sort="Painter, George" uniqKey="Painter G" first="George" last="Painter">George Painter</name>
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<name sortKey="Saindane, Manohar" sort="Saindane, Manohar" uniqKey="Saindane M" first="Manohar" last="Saindane">Manohar Saindane</name>
<name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name>
<name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C" last="Sims">Amy C. Sims</name>
<name sortKey="Stevens, Laura J" sort="Stevens, Laura J" uniqKey="Stevens L" first="Laura J" last="Stevens">Laura J. Stevens</name>
<name sortKey="Swanstrom, Ronald" sort="Swanstrom, Ronald" uniqKey="Swanstrom R" first="Ronald" last="Swanstrom">Ronald Swanstrom</name>
<name sortKey="Zhou, Shuntai" sort="Zhou, Shuntai" uniqKey="Zhou S" first="Shuntai" last="Zhou">Shuntai Zhou</name>
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