Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.
Identifieur interne : 000795 ( PubMed/Corpus ); précédent : 000794; suivant : 000796Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.
Auteurs : Emmie De Wit ; Friederike Feldmann ; Jacqueline Cronin ; Robert Jordan ; Atsushi Okumura ; Tina Thomas ; Dana Scott ; Tomas Cihlar ; Heinz FeldmannSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2020.
English descriptors
- KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (pharmacology), Alanine (analogs & derivatives), Alanine (pharmacology), Animals, Antiviral Agents (pharmacology), Betacoronavirus, Coronavirus Infections (drug therapy), Coronavirus Infections (prevention & control), Disease Models, Animal, Lung (pathology), Lung (virology), Macaca mulatta, Male, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (physiology), Pandemics, Pneumonia, Viral, Post-Exposure Prophylaxis, Viral Load, Virus Replication (drug effects).
- MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , pharmacology : Adenosine Monophosphate, Alanine, Antiviral Agents.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Replication.
- drug therapy : Coronavirus Infections.
- pathology : Lung.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- virology : Lung.
- Animals, Betacoronavirus, Disease Models, Animal, Macaca mulatta, Male, Pandemics, Pneumonia, Viral, Post-Exposure Prophylaxis, Viral Load.
Abstract
The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
DOI: 10.1073/pnas.1922083117
PubMed: 32054787
Links to Exploration step
pubmed:32054787Le document en format XML
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Feldmann</name><affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation></affiliation></author><author><name sortKey="Cronin, Jacqueline" sort="Cronin, Jacqueline" uniqKey="Cronin J" first="Jacqueline" last="Cronin">Jacqueline Cronin</name><affiliation><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation></affiliation></author><author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name><affiliation><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.</nlm:affiliation></affiliation></author><author><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name><affiliation><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Monophosphate (analogs & derivatives)</term><term>Adenosine Monophosphate (pharmacology)</term><term>Alanine (analogs & derivatives)</term><term>Alanine (pharmacology)</term><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Betacoronavirus</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (prevention & control)</term><term>Disease Models, Animal</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Macaca mulatta</term><term>Male</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Pandemics</term><term>Pneumonia, Viral</term><term>Post-Exposure Prophylaxis</term><term>Viral Load</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Betacoronavirus</term><term>Disease Models, Animal</term><term>Macaca mulatta</term><term>Male</term><term>Pandemics</term><term>Pneumonia, Viral</term><term>Post-Exposure Prophylaxis</term><term>Viral Load</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32054787</PMID><DateCompleted><Year>2020</Year><Month>04</Month><Day>01</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN><JournalIssue CitedMedium="Internet"><Volume>117</Volume><Issue>12</Issue><PubDate><Year>2020</Year><Month>03</Month><Day>24</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc. Natl. Acad. Sci. U.S.A.</ISOAbbreviation></Journal><ArticleTitle>Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.</ArticleTitle><Pagination><MedlinePgn>6771-6776</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.1922083117</ELocationID><Abstract><AbstractText>The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>de Wit</LastName><ForeName>Emmie</ForeName><Initials>E</Initials><Identifier Source="ORCID">0000-0002-9763-7758</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840; Emmie.deWit@nih.gov.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Friederike</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cronin</LastName><ForeName>Jacqueline</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordan</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okumura</LastName><ForeName>Atsushi</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thomas</LastName><ForeName>Tina</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Dana</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cihlar</LastName><ForeName>Tomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Heinz</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Proc Natl Acad Sci U S A</MedlineTA><NlmUniqueID>7505876</NlmUniqueID><ISSNLinking>0027-8424</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>3QKI37EEHE</RegistryNumber><NameOfSubstance UI="C000606551">remdesivir</NameOfSubstance></Chemical><Chemical><RegistryNumber>415SHH325A</RegistryNumber><NameOfSubstance UI="D000249">Adenosine Monophosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>OF5P57N2ZX</RegistryNumber><NameOfSubstance UI="D000409">Alanine</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000409" MajorTopicYN="N">Alanine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056990" MajorTopicYN="N">Post-Exposure Prophylaxis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">MERS-CoV</Keyword><Keyword MajorTopicYN="Y">animal model</Keyword><Keyword MajorTopicYN="Y">antiviral</Keyword><Keyword MajorTopicYN="Y">remdesivir</Keyword><Keyword MajorTopicYN="Y">therapy</Keyword></KeywordList><CoiStatement>Competing interest statement: The authors affiliated with Gilead Sciences are employees of the company and may own company stock; R.J. holds a patent on the use of remdesivir to treat Filovirus infections. 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