In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect.
Identifieur interne : 000C99 ( Main/Exploration ); précédent : 000C98; suivant : 000D00In 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 :
- Microbial pathogenesis [ 1096-1208 ] ; 2020.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Antiviraux (pharmacologie), Association de médicaments (méthodes), Azithromycine (pharmacologie), Betacoronavirus (effets des médicaments et des substances chimiques), Cellules Vero (MeSH), Humains (MeSH), Hydroxychloroquine (pharmacologie), Infections à coronavirus (traitement médicamenteux), Lignée cellulaire (MeSH), Pandémies (MeSH), Pneumopathie virale (traitement médicamenteux), Repositionnement des médicaments (MeSH), Réplication virale (effets des médicaments et des substances chimiques), Synergie des médicaments (MeSH).
- MESH :
- effets des médicaments et des substances chimiques : Betacoronavirus, Réplication virale.
- méthodes : Association de médicaments.
- pharmacologie : Antiviraux, Azithromycine, Hydroxychloroquine.
- traitement médicamenteux : Infections à coronavirus, Pneumopathie virale.
- Animaux, Cellules Vero, Humains, Lignée cellulaire, Pandémies, Repositionnement des médicaments, Synergie des médicaments.
English descriptors
- KwdEn :
- Animals (MeSH), Antiviral Agents (pharmacology), Azithromycin (pharmacology), Betacoronavirus (drug effects), Cell Line (MeSH), Chlorocebus aethiops (MeSH), Coronavirus Infections (drug therapy), Drug Repositioning (MeSH), Drug Synergism (MeSH), Drug Therapy, Combination (methods), Humans (MeSH), Hydroxychloroquine (pharmacology), Pandemics (MeSH), Pneumonia, Viral (drug therapy), Vero Cells (MeSH), Virus Replication (drug effects).
- MESH :
- chemical , pharmacology : Antiviral Agents, Azithromycin, Hydroxychloroquine.
- drug effects : Betacoronavirus, Virus Replication.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- methods : Drug Therapy, Combination.
- Animals, Cell Line, Chlorocebus aethiops, Drug Repositioning, Drug Synergism, Humans, Pandemics, Vero Cells.
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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<author><name sortKey="Jardot, Priscilla" sort="Jardot, Priscilla" uniqKey="Jardot P" first="Priscilla" last="Jardot">Priscilla Jardot</name>
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<author><name sortKey="Rolland, Clara" sort="Rolland, Clara" uniqKey="Rolland C" first="Clara" last="Rolland">Clara Rolland</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Boxberger, Manon" sort="Boxberger, Manon" uniqKey="Boxberger M" first="Manon" last="Boxberger">Manon Boxberger</name>
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<author><name sortKey="Wurtz, Nathalie" sort="Wurtz, Nathalie" uniqKey="Wurtz N" first="Nathalie" last="Wurtz">Nathalie Wurtz</name>
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<author><name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name>
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<author><name sortKey="Colson, Philippe" sort="Colson, Philippe" uniqKey="Colson P" first="Philippe" last="Colson">Philippe Colson</name>
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<author><name sortKey="La Scola, Bernard" sort="La Scola, Bernard" uniqKey="La Scola B" first="Bernard" last="La Scola">Bernard La Scola</name>
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<series><title level="j">Microbial pathogenesis</title>
<idno type="eISSN">1096-1208</idno>
<imprint><date when="2020" type="published">2020</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><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>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Association de médicaments (méthodes)</term>
<term>Azithromycine (pharmacologie)</term>
<term>Betacoronavirus (effets des médicaments et des substances chimiques)</term>
<term>Cellules Vero (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Hydroxychloroquine (pharmacologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Lignée cellulaire (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (traitement médicamenteux)</term>
<term>Repositionnement des médicaments (MeSH)</term>
<term>Réplication virale (effets des médicaments et des substances chimiques)</term>
<term>Synergie des médicaments (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Azithromycin</term>
<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Betacoronavirus</term>
<term>Réplication virale</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Therapy, Combination</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Association de médicaments</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
<term>Azithromycine</term>
<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<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>
</profileDesc>
</teiHeader>
<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>
<pubmed><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>
</MeshHeading>
<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>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>04</Month>
<Day>04</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>04</Month>
<Day>17</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>04</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>4</Month>
<Day>29</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>6</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>4</Month>
<Day>29</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">32344177</ArticleId>
<ArticleId IdType="pii">S0882-4010(20)30515-5</ArticleId>
<ArticleId IdType="doi">10.1016/j.micpath.2020.104228</ArticleId>
<ArticleId IdType="pmc">PMC7182748</ArticleId>
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<affiliations><list><country><li>France</li>
</country>
<region><li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement><li>Marseille</li>
</settlement>
</list>
<tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Andreani, Julien" sort="Andreani, Julien" uniqKey="Andreani J" first="Julien" last="Andreani">Julien Andreani</name>
</region>
<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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