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

Author

Listed:
  • 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
    Institut Pasteur)

  • 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
    Institut Pasteur
    Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur)

  • 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
    Institut Pasteur)

  • 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
    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)

  • 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
    Institut Pasteur)

  • 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)

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.

Suggested Citation

  • Pauline Maisonnasse & Jérémie Guedj & Vanessa Contreras & Sylvie Behillil & Caroline Solas & Romain Marlin & Thibaut Naninck & Andres Pizzorno & Julien Lemaitre & Antonio Gonçalves & Nidhal Kahlaoui &, 2020. "Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates," Nature, Nature, vol. 585(7826), pages 584-587, September.
  • Handle: RePEc:nat:nature:v:585:y:2020:i:7826:d:10.1038_s41586-020-2558-4
    DOI: 10.1038/s41586-020-2558-4
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    Cited by:

    1. Romain Marlin & Delphine Desjardins & Vanessa Contreras & Guillaume Lingas & Caroline Solas & Pierre Roques & Thibaut Naninck & Quentin Pascal & Sylvie Behillil & Pauline Maisonnasse & Julien Lemaitre, 2022. "Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Pauline Maisonnasse & Yoann Aldon & Aurélien Marc & Romain Marlin & Nathalie Dereuddre-Bosquet & Natalia A. Kuzmina & Alec W. Freyn & Jonne L. Snitselaar & Antonio Gonçalves & Tom G. Caniels & Judith , 2021. "COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models," Nature Communications, Nature, vol. 12(1), pages 1-10, December.

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