MersV1, PubMed, Curation, bibRecord, 000294

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

Identifieur interne : 000294 ( PubMed/Curation ); précédent : 000293; suivant : 000295

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

Auteurs : Timothy P. Sheahan [États-Unis] ; Amy C. Sims [États-Unis] ; Sarah R. Leist [États-Unis] ; Alexandra Sch Fer [États-Unis] ; John Won [États-Unis] ; Ariane J. Brown [États-Unis] ; Stephanie A. Montgomery [États-Unis] ; Alison Hogg [États-Unis] ; Darius Babusis [États-Unis] ; Michael O. Clarke [États-Unis] ; Jamie E. Spahn [États-Unis] ; Laura Bauer [États-Unis] ; Scott Sellers [États-Unis] ; Danielle Porter [États-Unis] ; Joy Y. Feng [États-Unis] ; Tomas Cihlar [États-Unis] ; Robert Jordan [États-Unis] ; Mark R. Denison [États-Unis] ; Ralph S. Baric [États-Unis]

Source :

Nature communications [ 2041-1723 ] ; 2020.

RBID : pubmed:31924756

Descripteurs français

KwdFr :
- AMP (analogues et dérivés), AMP (usage thérapeutique), Alanine (analogues et dérivés), Alanine (usage thérapeutique), Animaux, Antiviraux (usage thérapeutique), Association médicamenteuse, Carboxylesterase (génétique), Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (), Femelle, Humains, Infections à coronavirus (anatomopathologie), Infections à coronavirus (traitement médicamenteux), Interféron bêta (usage thérapeutique), Lopinavir (usage thérapeutique), Lésion pulmonaire (anatomopathologie), Mâle, Ritonavir (usage thérapeutique), Réplication virale (), Souris, Souris knockout.
MESH :
- analogues et dérivés : AMP, Alanine.
- anatomopathologie : Infections à coronavirus, Lésion pulmonaire.
- génétique : Carboxylesterase.
- traitement médicamenteux : Infections à coronavirus.
- usage thérapeutique : AMP, Alanine, Antiviraux, Interféron bêta, Lopinavir, Ritonavir.
- Animaux, Association médicamenteuse, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Humains, Mâle, Réplication virale, Souris, Souris knockout.

English descriptors

KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (therapeutic use), Alanine (analogs & derivatives), Alanine (therapeutic use), Animals, Antiviral Agents (therapeutic use), Carboxylesterase (genetics), Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Drug Combinations, Drug Development, Female, Humans, Interferon-beta (therapeutic use), Lopinavir (therapeutic use), Lung Injury (pathology), Male, Mice, Mice, Knockout, Middle East Respiratory Syndrome Coronavirus (drug effects), Ritonavir (therapeutic use), Viral Load, Virus Replication (drug effects).
MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , genetics : Carboxylesterase.
- chemical , therapeutic use : Adenosine Monophosphate, Alanine, Antiviral Agents, Interferon-beta, Lopinavir, Ritonavir.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Replication.
- drug therapy : Coronavirus Infections.
- pathology : Coronavirus Infections, Lung Injury.
- Animals, Drug Combinations, Drug Development, Female, Humans, Male, Mice, Mice, Knockout, Viral Load.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

DOI: 10.1038/s41467-019-13940-6
PubMed: 31924756

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Le document en format XML

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<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name>
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<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>
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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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<sourceDesc><biblStruct><analytic><title xml:lang="en">Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.</title>
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<author><name sortKey="Hogg, Alison" sort="Hogg, Alison" uniqKey="Hogg A" first="Alison" last="Hogg">Alison Hogg</name>
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<author><name sortKey="Babusis, Darius" sort="Babusis, Darius" uniqKey="Babusis D" first="Darius" last="Babusis">Darius Babusis</name>
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<author><name sortKey="Spahn, Jamie E" sort="Spahn, Jamie E" uniqKey="Spahn J" first="Jamie E" last="Spahn">Jamie E. Spahn</name>
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<author><name sortKey="Bauer, Laura" sort="Bauer, Laura" uniqKey="Bauer L" first="Laura" last="Bauer">Laura Bauer</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Gilead Sciences, Inc, Foster City, CA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Sellers, Scott" sort="Sellers, Scott" uniqKey="Sellers S" first="Scott" last="Sellers">Scott Sellers</name>
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<wicri:regionArea>Gilead Sciences, Inc, Foster City, CA</wicri:regionArea>
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<author><name sortKey="Porter, Danielle" sort="Porter, Danielle" uniqKey="Porter D" first="Danielle" last="Porter">Danielle Porter</name>
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<wicri:regionArea>Gilead Sciences, Inc, Foster City, CA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y" last="Feng">Joy Y. Feng</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Gilead Sciences, Inc, Foster City, CA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Gilead Sciences, Inc, Foster City, CA</wicri:regionArea>
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<author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name>
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<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>
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</author>
<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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<term>Adenosine Monophosphate (therapeutic use)</term>
<term>Alanine (analogs & derivatives)</term>
<term>Alanine (therapeutic use)</term>
<term>Animals</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>Carboxylesterase (genetics)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Drug Combinations</term>
<term>Drug Development</term>
<term>Female</term>
<term>Humans</term>
<term>Interferon-beta (therapeutic use)</term>
<term>Lopinavir (therapeutic use)</term>
<term>Lung Injury (pathology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term>
<term>Ritonavir (therapeutic use)</term>
<term>Viral Load</term>
<term>Virus Replication (drug effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP (analogues et dérivés)</term>
<term>AMP (usage thérapeutique)</term>
<term>Alanine (analogues et dérivés)</term>
<term>Alanine (usage thérapeutique)</term>
<term>Animaux</term>
<term>Antiviraux (usage thérapeutique)</term>
<term>Association médicamenteuse</term>
<term>Carboxylesterase (génétique)</term>
<term>Charge virale</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term>
<term>Femelle</term>
<term>Humains</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Interféron bêta (usage thérapeutique)</term>
<term>Lopinavir (usage thérapeutique)</term>
<term>Lésion pulmonaire (anatomopathologie)</term>
<term>Mâle</term>
<term>Ritonavir (usage thérapeutique)</term>
<term>Réplication virale ()</term>
<term>Souris</term>
<term>Souris knockout</term>
</keywords>
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<term>Alanine</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carboxylesterase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adenosine Monophosphate</term>
<term>Alanine</term>
<term>Antiviral Agents</term>
<term>Interferon-beta</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
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<term>Alanine</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Lésion pulmonaire</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="génétique" xml:lang="fr"><term>Carboxylesterase</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung Injury</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>AMP</term>
<term>Alanine</term>
<term>Antiviraux</term>
<term>Interféron bêta</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
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<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Drug Combinations</term>
<term>Drug Development</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Association médicamenteuse</term>
<term>Charge virale</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Réplication virale</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31924756</PMID>
<DateCompleted><Year>2020</Year>
<Month>04</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>07</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>11</Volume>
<Issue>1</Issue>
<PubDate><Year>2020</Year>
<Month>01</Month>
<Day>10</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.</ArticleTitle>
<Pagination><MedlinePgn>222</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-019-13940-6</ELocationID>
<Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sheahan</LastName>
<ForeName>Timothy P</ForeName>
<Initials>TP</Initials>
<Identifier Source="ORCID">0000-0001-9181-2183</Identifier>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. sheahan@email.unc.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="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, 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, 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, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Won</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 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, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Montgomery</LastName>
<ForeName>Stephanie A</ForeName>
<Initials>SA</Initials>
<Identifier Source="ORCID">0000-0001-8012-5302</Identifier>
<AffiliationInfo><Affiliation>Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hogg</LastName>
<ForeName>Alison</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Babusis</LastName>
<ForeName>Darius</ForeName>
<Initials>D</Initials>
<Identifier Source="ORCID">0000-0001-5599-1671</Identifier>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Clarke</LastName>
<ForeName>Michael O</ForeName>
<Initials>MO</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Spahn</LastName>
<ForeName>Jamie E</ForeName>
<Initials>JE</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bauer</LastName>
<ForeName>Laura</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sellers</LastName>
<ForeName>Scott</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Porter</LastName>
<ForeName>Danielle</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Feng</LastName>
<ForeName>Joy Y</ForeName>
<Initials>JY</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cihlar</LastName>
<ForeName>Tomas</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jordan</LastName>
<ForeName>Robert</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Gilead Sciences, Inc, Foster City, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Denison</LastName>
<ForeName>Mark R</ForeName>
<Initials>MR</Initials>
<Identifier Source="ORCID">0000-0003-2655-0900</Identifier>
<AffiliationInfo><Affiliation>Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, 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, USA. rbaric@email.unc.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>U54 CA156733</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 ES010126</GrantID>
<Acronym>ES</Acronym>
<Agency>NIEHS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI108197</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 CA016086</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<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>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>01</Month>
<Day>10</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nat Commun</MedlineTA>
<NlmUniqueID>101528555</NlmUniqueID>
<ISSNLinking>2041-1723</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004338">Drug Combinations</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C558899">lopinavir-ritonavir drug combination</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>2494G1JF75</RegistryNumber>
<NameOfSubstance UI="D061466">Lopinavir</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>77238-31-4</RegistryNumber>
<NameOfSubstance UI="D016899">Interferon-beta</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.1.1.1</RegistryNumber>
<NameOfSubstance UI="D043182">Carboxylesterase</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.1.1.1</RegistryNumber>
<NameOfSubstance UI="C469486">Ces1c protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>O3J8G9O825</RegistryNumber>
<NameOfSubstance UI="D019438">Ritonavir</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>OF5P57N2ZX</RegistryNumber>
<NameOfSubstance UI="D000409">Alanine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000409" MajorTopicYN="N">Alanine</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D043182" MajorTopicYN="N">Carboxylesterase</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000076722" MajorTopicYN="N">Drug Development</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016899" MajorTopicYN="N">Interferon-beta</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061466" MajorTopicYN="N">Lopinavir</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055370" MajorTopicYN="N">Lung Injury</DescriptorName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019438" MajorTopicYN="N">Ritonavir</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</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>
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<Day>03</Day>
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<Month>12</Month>
<Day>07</Day>
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Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV.

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