CovidChloroV1, Main, Corpus, bibRecord, 000650

Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.

Identifieur interne : 000650 ( Main/Corpus ); précédent : 000649; suivant : 000651

Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.

Auteurs : Tesia Bobrowski ; Lu Chen ; Richard T. Eastman ; Zina Itkin ; Paul Shinn ; Catherine Z. Chen ; Hui Guo ; Wei Zheng ; Sam Michael ; Anton Simeonov ; Matthew D. Hall ; Alexey V. Zakharov ; Eugene N. Muratov

Source :

Molecular therapy : the journal of the American Society of Gene Therapy [ 1525-0024 ] ; 2021.

RBID : pubmed:33333292

English descriptors

KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (therapeutic use), Alanine (analogs & derivatives), Alanine (therapeutic use), Antiviral Agents (therapeutic use), COVID-19 (drug therapy), Drug Combinations (MeSH), Drug Synergism (MeSH), Humans (MeSH), Hydroxychloroquine (therapeutic use), SARS-CoV-2 (drug effects).
MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , therapeutic use : Adenosine Monophosphate, Alanine, Antiviral Agents, Hydroxychloroquine.
- drug effects : SARS-CoV-2.
- drug therapy : COVID-19.
- chemical : Drug Combinations, Drug Synergism, Humans.

Abstract

Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19.

DOI: 10.1016/j.ymthe.2020.12.016
PubMed: 33333292
PubMed Central: PMC7834738

Links to Exploration step

pubmed:33333292

Le document en format XML

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<author><name sortKey="Bobrowski, Tesia" sort="Bobrowski, Tesia" uniqKey="Bobrowski T" first="Tesia" last="Bobrowski">Tesia Bobrowski</name>
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<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
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<author><name sortKey="Eastman, Richard T" sort="Eastman, Richard T" uniqKey="Eastman R" first="Richard T" last="Eastman">Richard T. Eastman</name>
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<author><name sortKey="Itkin, Zina" sort="Itkin, Zina" uniqKey="Itkin Z" first="Zina" last="Itkin">Zina Itkin</name>
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<author><name sortKey="Shinn, Paul" sort="Shinn, Paul" uniqKey="Shinn P" first="Paul" last="Shinn">Paul Shinn</name>
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<author><name sortKey="Chen, Catherine Z" sort="Chen, Catherine Z" uniqKey="Chen C" first="Catherine Z" last="Chen">Catherine Z. Chen</name>
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<author><name sortKey="Simeonov, Anton" sort="Simeonov, Anton" uniqKey="Simeonov A" first="Anton" last="Simeonov">Anton Simeonov</name>
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<author><name sortKey="Hall, Matthew D" sort="Hall, Matthew D" uniqKey="Hall M" first="Matthew D" last="Hall">Matthew D. Hall</name>
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<author><name sortKey="Zakharov, Alexey V" sort="Zakharov, Alexey V" uniqKey="Zakharov A" first="Alexey V" last="Zakharov">Alexey V. Zakharov</name>
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<author><name sortKey="Zakharov, Alexey V" sort="Zakharov, Alexey V" uniqKey="Zakharov A" first="Alexey V" last="Zakharov">Alexey V. Zakharov</name>
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<term>Alanine (therapeutic use)</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>COVID-19 (drug therapy)</term>
<term>Drug Combinations (MeSH)</term>
<term>Drug Synergism (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (therapeutic use)</term>
<term>SARS-CoV-2 (drug effects)</term>
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<front><div type="abstract" xml:lang="en">Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19.</div>
</front>
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<Abstract><AbstractText>Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19.</AbstractText>
<CopyrightInformation>Copyright © 2020 The American Society of Gene and Cell Therapy. All rights reserved.</CopyrightInformation>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bobrowski</LastName>
<ForeName>Tesia</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Lu</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences (NCATS), 9800 Medical Center Drive, Rockville, MD 20850, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Eastman</LastName>
<ForeName>Richard T</ForeName>
<Initials>RT</Initials>
<AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences (NCATS), 9800 Medical Center Drive, Rockville, MD 20850, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Itkin</LastName>
<ForeName>Zina</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences (NCATS), 9800 Medical Center Drive, Rockville, MD 20850, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>Paul</ForeName>
<Initials>P</Initials>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Chen</LastName>
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<Author ValidYN="Y"><LastName>Zheng</LastName>
<ForeName>Wei</ForeName>
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<Initials>S</Initials>
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</AffiliationInfo>
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<ForeName>Anton</ForeName>
<Initials>A</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hall</LastName>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zakharov</LastName>
<ForeName>Alexey V</ForeName>
<Initials>AV</Initials>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Muratov</LastName>
<ForeName>Eugene N</ForeName>
<Initials>EN</Initials>
<AffiliationInfo><Affiliation>Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: murik@email.unc.edu.</Affiliation>
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<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="UpdateOf"><RefSource>bioRxiv. 2020 Jun 30;:</RefSource>
<PMID Version="1">32637956</PMID>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
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<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
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<MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</DescriptorName>
</MeshHeading>
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<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
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</MeshHeading>
</MeshHeadingList>
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<Keyword MajorTopicYN="Y">CPE assay</Keyword>
<Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="Y">combination therapy</Keyword>
<Keyword MajorTopicYN="Y">drug combinations</Keyword>
<Keyword MajorTopicYN="Y">drug repurposing</Keyword>
<Keyword MajorTopicYN="Y">drug synergy</Keyword>
<Keyword MajorTopicYN="Y">in silico design</Keyword>
<Keyword MajorTopicYN="Y">knowledge mining</Keyword>
<Keyword MajorTopicYN="Y">nitazoxanide remdesivir combo</Keyword>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>09</Month>
<Day>03</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>11</Month>
<Day>15</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>12</Month>
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Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.

Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.

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