Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.
Identifieur interne : 000D89 ( Main/Exploration ); précédent : 000D88; suivant : 000D90Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.
Auteurs : Pauline Maisonnasse [France] ; Jérémie Guedj [France] ; Vanessa Contreras [France] ; Sylvie Behillil [France] ; Caroline Solas [France] ; Romain Marlin [France] ; Thibaut Naninck [France] ; Andres Pizzorno [France] ; Julien Lemaitre [France] ; Antonio Gonçalves [France] ; Nidhal Kahlaoui [France] ; Olivier Terrier [France] ; Raphael Ho Tsong Fang [France] ; Vincent Enouf [France] ; Nathalie Dereuddre-Bosquet [France] ; Angela Brisebarre [France] ; Franck Touret [France] ; Catherine Chapon [France] ; Bruno Hoen [France] ; Bruno Lina [France] ; Manuel Rosa Calatrava [France] ; Sylvie Van Der Werf [France] ; Xavier De Lamballerie [France] ; Roger Le Grand [France]Source :
- Nature [ 1476-4687 ] ; 2020.
Abstract
Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.
DOI: 10.1038/s41586-020-2558-4
PubMed: 32698191
Affiliations:
- France
- Auvergne-Rhône-Alpes, Provence-Alpes-Côte d'Azur, Rhône-Alpes, Île-de-France
- Lyon, Marseille, Paris
- Université d'Aix-Marseille
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Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Marlin, Romain" sort="Marlin, Romain" uniqKey="Marlin R" first="Romain" last="Marlin">Romain Marlin</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Naninck, Thibaut" sort="Naninck, Thibaut" uniqKey="Naninck T" first="Thibaut" last="Naninck">Thibaut Naninck</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Lemaitre, Julien" sort="Lemaitre, Julien" uniqKey="Lemaitre J" first="Julien" last="Lemaitre">Julien Lemaitre</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Goncalves, Antonio" sort="Goncalves, Antonio" uniqKey="Goncalves A" first="Antonio" last="Gonçalves">Antonio Gonçalves</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, Inserm, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kahlaoui, Nidhal" sort="Kahlaoui, Nidhal" uniqKey="Kahlaoui N" first="Nidhal" last="Kahlaoui">Nidhal Kahlaoui</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Fang, Raphael Ho Tsong" sort="Fang, Raphael Ho Tsong" uniqKey="Fang R" first="Raphael Ho Tsong" last="Fang">Raphael Ho Tsong Fang</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dereuddre Bosquet, Nathalie" sort="Dereuddre Bosquet, Nathalie" uniqKey="Dereuddre Bosquet N" first="Nathalie" last="Dereuddre-Bosquet">Nathalie Dereuddre-Bosquet</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name><affiliation wicri:level="4"><nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents (UVE), Aix-Marseille Université, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Chapon, Catherine" sort="Chapon, Catherine" uniqKey="Chapon C" first="Catherine" last="Chapon">Catherine Chapon</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Hoen, Bruno" sort="Hoen, Bruno" uniqKey="Hoen B" first="Bruno" last="Hoen">Bruno Hoen</name><affiliation wicri:level="3"><nlm:affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Calatrava, Manuel Rosa" sort="Calatrava, Manuel Rosa" uniqKey="Calatrava M" first="Manuel Rosa" last="Calatrava">Manuel Rosa Calatrava</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name><affiliation wicri:level="4"><nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents (UVE), Aix-Marseille Université, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32698191</idno><idno type="pmid">32698191</idno><idno type="doi">10.1038/s41586-020-2558-4</idno><idno type="wicri:Area/Main/Corpus">000870</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000870</idno><idno type="wicri:Area/Main/Curation">000870</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000870</idno><idno type="wicri:Area/Main/Exploration">000870</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.</title><author><name sortKey="Maisonnasse, Pauline" sort="Maisonnasse, Pauline" uniqKey="Maisonnasse P" first="Pauline" last="Maisonnasse">Pauline Maisonnasse</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Guedj, Jeremie" sort="Guedj, Jeremie" uniqKey="Guedj J" first="Jérémie" last="Guedj">Jérémie Guedj</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, Inserm, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Contreras, Vanessa" sort="Contreras, Vanessa" uniqKey="Contreras V" first="Vanessa" last="Contreras">Vanessa Contreras</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Behillil, Sylvie" sort="Behillil, Sylvie" uniqKey="Behillil S" first="Sylvie" last="Behillil">Sylvie Behillil</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Marlin, Romain" sort="Marlin, Romain" uniqKey="Marlin R" first="Romain" last="Marlin">Romain Marlin</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Naninck, Thibaut" sort="Naninck, Thibaut" uniqKey="Naninck T" first="Thibaut" last="Naninck">Thibaut Naninck</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Lemaitre, Julien" sort="Lemaitre, Julien" uniqKey="Lemaitre J" first="Julien" last="Lemaitre">Julien Lemaitre</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Goncalves, Antonio" sort="Goncalves, Antonio" uniqKey="Goncalves A" first="Antonio" last="Gonçalves">Antonio Gonçalves</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, IAME, Inserm, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kahlaoui, Nidhal" sort="Kahlaoui, Nidhal" uniqKey="Kahlaoui N" first="Nidhal" last="Kahlaoui">Nidhal Kahlaoui</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Fang, Raphael Ho Tsong" sort="Fang, Raphael Ho Tsong" uniqKey="Fang R" first="Raphael Ho Tsong" last="Fang">Raphael Ho Tsong Fang</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dereuddre Bosquet, Nathalie" sort="Dereuddre Bosquet, Nathalie" uniqKey="Dereuddre Bosquet N" first="Nathalie" last="Dereuddre-Bosquet">Nathalie Dereuddre-Bosquet</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name><affiliation wicri:level="4"><nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents (UVE), Aix-Marseille Université, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Chapon, Catherine" sort="Chapon, Catherine" uniqKey="Chapon C" first="Catherine" last="Chapon">Catherine Chapon</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author><author><name sortKey="Hoen, Bruno" sort="Hoen, Bruno" uniqKey="Hoen B" first="Bruno" last="Hoen">Bruno Hoen</name><affiliation wicri:level="3"><nlm:affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Calatrava, Manuel Rosa" sort="Calatrava, Manuel Rosa" uniqKey="Calatrava M" first="Manuel Rosa" last="Calatrava">Manuel Rosa Calatrava</name><affiliation wicri:level="3"><nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name><affiliation wicri:level="4"><nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents (UVE), Aix-Marseille Université, 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><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name><affiliation wicri:level="1"><nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses</wicri:regionArea><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion><wicri:noRegion>Fontenay-aux-Roses</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</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">Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease<sup>1-3</sup>. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19<sup>4-7</sup>. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32698191</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN><JournalIssue CitedMedium="Internet"><Volume>585</Volume><Issue>7826</Issue><PubDate><Year>2020</Year><Month>09</Month></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.</ArticleTitle><Pagination><MedlinePgn>584-587</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41586-020-2558-4</ELocationID><Abstract><AbstractText>Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease<sup>1-3</sup>. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19<sup>4-7</sup>. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Maisonnasse</LastName><ForeName>Pauline</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0002-0555-207X</Identifier><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guedj</LastName><ForeName>Jérémie</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-5534-5482</Identifier><AffiliationInfo><Affiliation>Université de Paris, IAME, Inserm, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Contreras</LastName><ForeName>Vanessa</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Behillil</LastName><ForeName>Sylvie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Solas</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marlin</LastName><ForeName>Romain</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Naninck</LastName><ForeName>Thibaut</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pizzorno</LastName><ForeName>Andres</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lemaitre</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gonçalves</LastName><ForeName>Antonio</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-8759-2429</Identifier><AffiliationInfo><Affiliation>Université de Paris, IAME, Inserm, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kahlaoui</LastName><ForeName>Nidhal</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Terrier</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><Identifier Source="ORCID">0000-0001-9393-7684</Identifier><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Raphael Ho Tsong</ForeName><Initials>RHT</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Enouf</LastName><ForeName>Vincent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dereuddre-Bosquet</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0001-6682-6313</Identifier><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brisebarre</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</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 Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chapon</LastName><ForeName>Catherine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoen</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lina</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Calatrava</LastName><ForeName>Manuel Rosa</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van der Werf</LastName><ForeName>Sylvie</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-1148-4456</Identifier><AffiliationInfo><Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Lamballerie</LastName><ForeName>Xavier</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Grand</LastName><ForeName>Roger</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0002-4928-4484</Identifier><AffiliationInfo><Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nature</MedlineTA><NlmUniqueID>0410462</NlmUniqueID><ISSNLinking>0028-0836</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>07</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>7</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>7</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32698191</ArticleId><ArticleId IdType="doi">10.1038/s41586-020-2558-4</ArticleId><ArticleId IdType="pii">10.1038/s41586-020-2558-4</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Provence-Alpes-Côte d'Azur</li><li>Rhône-Alpes</li><li>Île-de-France</li></region><settlement><li>Lyon</li><li>Marseille</li><li>Paris</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Maisonnasse, Pauline" sort="Maisonnasse, Pauline" uniqKey="Maisonnasse P" first="Pauline" last="Maisonnasse">Pauline Maisonnasse</name></noRegion><name sortKey="Behillil, Sylvie" sort="Behillil, Sylvie" uniqKey="Behillil S" first="Sylvie" last="Behillil">Sylvie Behillil</name><name sortKey="Behillil, Sylvie" sort="Behillil, Sylvie" uniqKey="Behillil S" first="Sylvie" last="Behillil">Sylvie Behillil</name><name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name><name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name><name sortKey="Calatrava, Manuel Rosa" sort="Calatrava, Manuel Rosa" uniqKey="Calatrava M" first="Manuel Rosa" last="Calatrava">Manuel Rosa Calatrava</name><name sortKey="Chapon, Catherine" sort="Chapon, Catherine" uniqKey="Chapon C" first="Catherine" last="Chapon">Catherine Chapon</name><name sortKey="Contreras, Vanessa" sort="Contreras, Vanessa" uniqKey="Contreras V" first="Vanessa" last="Contreras">Vanessa Contreras</name><name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name><name sortKey="Dereuddre Bosquet, Nathalie" sort="Dereuddre Bosquet, Nathalie" uniqKey="Dereuddre Bosquet N" first="Nathalie" last="Dereuddre-Bosquet">Nathalie Dereuddre-Bosquet</name><name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name><name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name><name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name><name sortKey="Fang, Raphael Ho Tsong" sort="Fang, Raphael Ho Tsong" uniqKey="Fang R" first="Raphael Ho Tsong" last="Fang">Raphael Ho Tsong Fang</name><name sortKey="Goncalves, Antonio" sort="Goncalves, Antonio" uniqKey="Goncalves A" first="Antonio" last="Gonçalves">Antonio Gonçalves</name><name sortKey="Guedj, Jeremie" sort="Guedj, Jeremie" uniqKey="Guedj J" first="Jérémie" last="Guedj">Jérémie Guedj</name><name sortKey="Hoen, Bruno" sort="Hoen, Bruno" uniqKey="Hoen B" first="Bruno" last="Hoen">Bruno Hoen</name><name sortKey="Kahlaoui, Nidhal" sort="Kahlaoui, Nidhal" uniqKey="Kahlaoui N" first="Nidhal" last="Kahlaoui">Nidhal Kahlaoui</name><name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name><name sortKey="Lemaitre, Julien" sort="Lemaitre, Julien" uniqKey="Lemaitre J" first="Julien" last="Lemaitre">Julien Lemaitre</name><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><name sortKey="Marlin, Romain" sort="Marlin, Romain" uniqKey="Marlin R" first="Romain" last="Marlin">Romain Marlin</name><name sortKey="Naninck, Thibaut" sort="Naninck, Thibaut" uniqKey="Naninck T" first="Thibaut" last="Naninck">Thibaut Naninck</name><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name><name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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