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In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect.

Identifieur interne : 000C99 ( Main/Exploration ); précédent : 000C98; suivant : 000D00

In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect.

Auteurs : Julien Andreani [France] ; Marion Le Bideau [France] ; Isabelle Duflot [France] ; Priscilla Jardot [France] ; Clara Rolland [France] ; Manon Boxberger [France] ; Nathalie Wurtz [France] ; Jean-Marc Rolain [France] ; Philippe Colson [France] ; Bernard La Scola [France] ; Didier Raoult [France]

Source :

RBID : pubmed:32344177

Descripteurs français

English descriptors

Abstract

Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.

DOI: 10.1016/j.micpath.2020.104228
PubMed: 32344177
PubMed Central: PMC7182748


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Animals (MeSH)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Azithromycin (pharmacology)</term>
<term>Betacoronavirus (drug effects)</term>
<term>Cell Line (MeSH)</term>
<term>Chlorocebus aethiops (MeSH)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Drug Repositioning (MeSH)</term>
<term>Drug Synergism (MeSH)</term>
<term>Drug Therapy, Combination (methods)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (drug therapy)</term>
<term>Vero Cells (MeSH)</term>
<term>Virus Replication (drug effects)</term>
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<term>Azithromycine (pharmacologie)</term>
<term>Betacoronavirus (effets des médicaments et des substances chimiques)</term>
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<term>Humains (MeSH)</term>
<term>Hydroxychloroquine (pharmacologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Lignée cellulaire (MeSH)</term>
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<term>Pneumopathie virale (traitement médicamenteux)</term>
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<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Drug Repositioning</term>
<term>Drug Synergism</term>
<term>Humans</term>
<term>Pandemics</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Cellules Vero</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Pandémies</term>
<term>Repositionnement des médicaments</term>
<term>Synergie des médicaments</term>
</keywords>
</textClass>
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<front>
<div type="abstract" xml:lang="en">Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.</div>
</front>
</TEI>
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<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">32344177</PMID>
<DateCompleted>
<Year>2020</Year>
<Month>06</Month>
<Day>18</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>06</Month>
<Day>18</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1096-1208</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>145</Volume>
<PubDate>
<Year>2020</Year>
<Month>Aug</Month>
</PubDate>
</JournalIssue>
<Title>Microbial pathogenesis</Title>
<ISOAbbreviation>Microb. Pathog.</ISOAbbreviation>
</Journal>
<ArticleTitle>In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect.</ArticleTitle>
<Pagination>
<MedlinePgn>104228</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0882-4010(20)30515-5</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.micpath.2020.104228</ELocationID>
<Abstract>
<AbstractText>Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.</AbstractText>
<CopyrightInformation>Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Andreani</LastName>
<ForeName>Julien</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Le Bideau</LastName>
<ForeName>Marion</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Duflot</LastName>
<ForeName>Isabelle</ForeName>
<Initials>I</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jardot</LastName>
<ForeName>Priscilla</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rolland</LastName>
<ForeName>Clara</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Boxberger</LastName>
<ForeName>Manon</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wurtz</LastName>
<ForeName>Nathalie</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rolain</LastName>
<ForeName>Jean-Marc</ForeName>
<Initials>JM</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Colson</LastName>
<ForeName>Philippe</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>La Scola</LastName>
<ForeName>Bernard</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France. Electronic address: bernard.la-scola@univ-amu.fr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Raoult</LastName>
<ForeName>Didier</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>IHU-Méditerranée Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France. Electronic address: didier.raoult@gmail.com.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2020</Year>
<Month>04</Month>
<Day>25</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>England</Country>
<MedlineTA>Microb Pathog</MedlineTA>
<NlmUniqueID>8606191</NlmUniqueID>
<ISSNLinking>0882-4010</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>83905-01-5</RegistryNumber>
<NameOfSubstance UI="D017963">Azithromycin</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="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="D017963" MajorTopicYN="N">Azithromycin</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D058492" MajorTopicYN="N">Drug Repositioning</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004357" MajorTopicYN="N">Drug Synergism</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004359" MajorTopicYN="N">Drug Therapy, Combination</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
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<MeshHeading>
<DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</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="N">2019-nCoV</Keyword>
<Keyword MajorTopicYN="N">Azithromycin</Keyword>
<Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">Hydroxychloroquine</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">Vero E6</Keyword>
</KeywordList>
<CoiStatement>Declaration of competing interest Authors would like to declare that Didier Raoult is a consultant in microbiology for Hitachi High-Tech Corporation. Funding sources had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The others authors declare no conflict of interest.</CoiStatement>
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<Year>2020</Year>
<Month>04</Month>
<Day>17</Day>
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<Month>04</Month>
<Day>22</Day>
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<affiliations>
<list>
<country>
<li>France</li>
</country>
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<li>Provence-Alpes-Côte d'Azur</li>
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<tree>
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<region name="Provence-Alpes-Côte d'Azur">
<name sortKey="Andreani, Julien" sort="Andreani, Julien" uniqKey="Andreani J" first="Julien" last="Andreani">Julien Andreani</name>
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<name sortKey="Boxberger, Manon" sort="Boxberger, Manon" uniqKey="Boxberger M" first="Manon" last="Boxberger">Manon Boxberger</name>
<name sortKey="Colson, Philippe" sort="Colson, Philippe" uniqKey="Colson P" first="Philippe" last="Colson">Philippe Colson</name>
<name sortKey="Duflot, Isabelle" sort="Duflot, Isabelle" uniqKey="Duflot I" first="Isabelle" last="Duflot">Isabelle Duflot</name>
<name sortKey="Jardot, Priscilla" sort="Jardot, Priscilla" uniqKey="Jardot P" first="Priscilla" last="Jardot">Priscilla Jardot</name>
<name sortKey="La Scola, Bernard" sort="La Scola, Bernard" uniqKey="La Scola B" first="Bernard" last="La Scola">Bernard La Scola</name>
<name sortKey="Le Bideau, Marion" sort="Le Bideau, Marion" uniqKey="Le Bideau M" first="Marion" last="Le Bideau">Marion Le Bideau</name>
<name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name>
<name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name>
<name sortKey="Rolland, Clara" sort="Rolland, Clara" uniqKey="Rolland C" first="Clara" last="Rolland">Clara Rolland</name>
<name sortKey="Wurtz, Nathalie" sort="Wurtz, Nathalie" uniqKey="Wurtz N" first="Nathalie" last="Wurtz">Nathalie Wurtz</name>
</country>
</tree>
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</record>

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