Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.
Identifieur interne : 000809 ( Main/Exploration ); précédent : 000808; suivant : 000810Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.
Auteurs : Ashleigh Shannon [France] ; Barbara Selisko [France] ; Nhung-Thi-Tuyet Le [France] ; Johanna Huchting [Allemagne] ; Franck Touret [France] ; Géraldine Piorkowski [France] ; Véronique Fattorini [France] ; François Ferron [France] ; Etienne Decroly [France] ; Chris Meier [Allemagne] ; Bruno Coutard [France] ; Olve Peersen [États-Unis] ; Bruno Canard [France]Source :
- Nature communications [ 2041-1723 ] ; 2020.
Abstract
The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.
DOI: 10.1038/s41467-020-18463-z
PubMed: 32943628
Affiliations:
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IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Peersen, Olve" sort="Peersen, Olve" uniqKey="Peersen O" first="Olve" last="Peersen">Olve Peersen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870, USA. Olve.Peersen@colostate.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870</wicri:regionArea><wicri:noRegion>80523-1870</wicri:noRegion></affiliation></author><author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France. bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32943628</idno><idno type="pmid">32943628</idno><idno type="doi">10.1038/s41467-020-18463-z</idno><idno type="wicri:Area/Main/Corpus">000090</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000090</idno><idno type="wicri:Area/Main/Curation">000090</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000090</idno><idno type="wicri:Area/Main/Exploration">000090</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.</title><author><name sortKey="Shannon, Ashleigh" sort="Shannon, Ashleigh" uniqKey="Shannon A" first="Ashleigh" last="Shannon">Ashleigh Shannon</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Selisko, Barbara" sort="Selisko, Barbara" uniqKey="Selisko B" first="Barbara" last="Selisko">Barbara Selisko</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Le, Nhung Thi Tuyet" sort="Le, Nhung Thi Tuyet" uniqKey="Le N" first="Nhung-Thi-Tuyet" last="Le">Nhung-Thi-Tuyet Le</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Huchting, Johanna" sort="Huchting, Johanna" uniqKey="Huchting J" first="Johanna" last="Huchting">Johanna Huchting</name><affiliation wicri:level="3"><nlm:affiliation>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg</wicri:regionArea><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name><affiliation wicri:level="3"><nlm:affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Piorkowski, Geraldine" sort="Piorkowski, Geraldine" uniqKey="Piorkowski G" first="Géraldine" last="Piorkowski">Géraldine Piorkowski</name><affiliation wicri:level="3"><nlm:affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Fattorini, Veronique" sort="Fattorini, Veronique" uniqKey="Fattorini V" first="Véronique" last="Fattorini">Véronique Fattorini</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Ferron, Francois" sort="Ferron, Francois" uniqKey="Ferron F" first="François" last="Ferron">François Ferron</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Meier, Chris" sort="Meier, Chris" uniqKey="Meier C" first="Chris" last="Meier">Chris Meier</name><affiliation wicri:level="3"><nlm:affiliation>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg</wicri:regionArea><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Coutard, Bruno" sort="Coutard, Bruno" uniqKey="Coutard B" first="Bruno" last="Coutard">Bruno Coutard</name><affiliation wicri:level="3"><nlm:affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Peersen, Olve" sort="Peersen, Olve" uniqKey="Peersen O" first="Olve" last="Peersen">Olve Peersen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870, USA. Olve.Peersen@colostate.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870</wicri:regionArea><wicri:noRegion>80523-1870</wicri:noRegion></affiliation></author><author><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><affiliation wicri:level="3"><nlm:affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France. bruno.canard@afmb.univ-mrs.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32943628</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>21</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>09</Month><Day>17</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.</ArticleTitle><Pagination><MedlinePgn>4682</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-020-18463-z</ELocationID><Abstract><AbstractText>The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shannon</LastName><ForeName>Ashleigh</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0003-4290-8247</Identifier><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Selisko</LastName><ForeName>Barbara</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0001-7135-4357</Identifier><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le</LastName><ForeName>Nhung-Thi-Tuyet</ForeName><Initials>NT</Initials><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huchting</LastName><ForeName>Johanna</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-6368-3273</Identifier><AffiliationInfo><Affiliation>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Touret</LastName><ForeName>Franck</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0002-4734-2249</Identifier><AffiliationInfo><Affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Piorkowski</LastName><ForeName>Géraldine</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fattorini</LastName><ForeName>Véronique</ForeName><Initials>V</Initials><Identifier Source="ORCID">0000-0001-6420-7949</Identifier><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferron</LastName><ForeName>François</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0002-8351-4992</Identifier><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Decroly</LastName><ForeName>Etienne</ForeName><Initials>E</Initials><Identifier Source="ORCID">0000-0002-6046-024X</Identifier><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meier</LastName><ForeName>Chris</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Faculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coutard</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peersen</LastName><ForeName>Olve</ForeName><Initials>O</Initials><Identifier Source="ORCID">0000-0001-6208-2660</Identifier><AffiliationInfo><Affiliation>Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870, USA. Olve.Peersen@colostate.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Canard</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France. bruno.canard@afmb.univ-mrs.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI059130</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>18</Day><Hour>5</Hour><Minute>43</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32943628</ArticleId><ArticleId IdType="doi">10.1038/s41467-020-18463-z</ArticleId><ArticleId IdType="pii">10.1038/s41467-020-18463-z</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>France</li><li>États-Unis</li></country><region><li>Hambourg</li><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Hambourg</li><li>Marseille</li></settlement></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Shannon, Ashleigh" sort="Shannon, Ashleigh" uniqKey="Shannon A" first="Ashleigh" last="Shannon">Ashleigh Shannon</name></region><name sortKey="Canard, Bruno" sort="Canard, Bruno" uniqKey="Canard B" first="Bruno" last="Canard">Bruno Canard</name><name sortKey="Coutard, Bruno" sort="Coutard, Bruno" uniqKey="Coutard B" first="Bruno" last="Coutard">Bruno Coutard</name><name sortKey="Decroly, Etienne" sort="Decroly, Etienne" uniqKey="Decroly E" first="Etienne" last="Decroly">Etienne Decroly</name><name sortKey="Fattorini, Veronique" sort="Fattorini, Veronique" uniqKey="Fattorini V" first="Véronique" last="Fattorini">Véronique Fattorini</name><name sortKey="Ferron, Francois" sort="Ferron, Francois" uniqKey="Ferron F" first="François" last="Ferron">François Ferron</name><name sortKey="Le, Nhung Thi Tuyet" sort="Le, Nhung Thi Tuyet" uniqKey="Le N" first="Nhung-Thi-Tuyet" last="Le">Nhung-Thi-Tuyet Le</name><name sortKey="Piorkowski, Geraldine" sort="Piorkowski, Geraldine" uniqKey="Piorkowski G" first="Géraldine" last="Piorkowski">Géraldine Piorkowski</name><name sortKey="Selisko, Barbara" sort="Selisko, Barbara" uniqKey="Selisko B" first="Barbara" last="Selisko">Barbara Selisko</name><name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name></country><country name="Allemagne"><region name="Hambourg"><name sortKey="Huchting, Johanna" sort="Huchting, Johanna" uniqKey="Huchting J" first="Johanna" last="Huchting">Johanna Huchting</name></region><name sortKey="Meier, Chris" sort="Meier, Chris" uniqKey="Meier C" first="Chris" last="Meier">Chris Meier</name></country><country name="États-Unis"><noRegion><name sortKey="Peersen, Olve" sort="Peersen, Olve" uniqKey="Peersen O" first="Olve" last="Peersen">Olve Peersen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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