Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates

Pauline Maisonnasse, Jérémie Guedj, Vanessa Contreras, Sylvie Behillil, Caroline Solas, Romain Marlin, Thibaut Naninck, Andres Pizzorno, Julien Lemaitre, Antonio Gonçalves, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fang, Vincent Enouf, Nathalie Dereuddre-Bosquet, Angela Brisebarre, Franck Touret, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa Calatrava, Sylvie Werf, Xavier Lamballerie and Roger Le Grand ()
Additional contact information
Pauline Maisonnasse: Université Paris-Saclay, Inserm, CEA
Jérémie Guedj: Université de Paris, IAME, Inserm
Vanessa Contreras: Université Paris-Saclay, Inserm, CEA
Sylvie Behillil: Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
Caroline Solas: Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone
Romain Marlin: Université Paris-Saclay, Inserm, CEA
Thibaut Naninck: Université Paris-Saclay, Inserm, CEA
Andres Pizzorno: CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Julien Lemaitre: Université Paris-Saclay, Inserm, CEA
Antonio Gonçalves: Université de Paris, IAME, Inserm
Nidhal Kahlaoui: Université Paris-Saclay, Inserm, CEA
Olivier Terrier: CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Raphael Ho Tsong Fang: Université Paris-Saclay, Inserm, CEA
Vincent Enouf: Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
Nathalie Dereuddre-Bosquet: Université Paris-Saclay, Inserm, CEA
Angela Brisebarre: Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
Franck Touret: Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection
Catherine Chapon: Université Paris-Saclay, Inserm, CEA
Bruno Hoen: Emerging Diseases Epidemiology Unit, Institut Pasteur
Bruno Lina: CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Manuel Rosa Calatrava: CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
Sylvie Werf: Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
Xavier Lamballerie: Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection
Roger Le Grand: Université Paris-Saclay, Inserm, CEA

Nature, 2020, vol. 585, issue 7826, 584-587

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2558-4

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