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Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates

Author

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  • Romain Marlin

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Delphine Desjardins

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Vanessa Contreras

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Guillaume Lingas

    (Université de Paris, INSERM, IAME)

  • Caroline Solas

    (Aix-Marseille Univ, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Laboratoire de Pharmacocinétique et Toxicologie, Hôpital La Timone)

  • Pierre Roques

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT)
    Virology Unit, Institut Pasteur de Guinée)

  • Thibaut Naninck

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Quentin Pascal

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Sylvie Behillil

    (Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
    Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur)

  • Pauline Maisonnasse

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Julien Lemaitre

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Nidhal Kahlaoui

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Benoit Delache

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Andrés Pizzorno

    (CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon)

  • Antoine Nougairede

    (Unité des Virus Emergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection)

  • Camille Ludot

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Olivier Terrier

    (CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon)

  • Nathalie Dereuddre-Bosquet

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Francis Relouzat

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Catherine Chapon

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Raphael Ho Tsong Fang

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

  • Sylvie Werf

    (Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris
    Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur)

  • Manuel Rosa Calatrava

    (CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon
    VirNext, Université Claude Bernard Lyon 1, Faculté de Médecine Laennec)

  • Denis Malvy

    (University hopsital, Bordeaux & Inserm 1219/IRD, Bordeaux University)

  • Xavier Lamballerie

    (Unité des Virus Emergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Méditerranée Infection)

  • Jeremie Guedj

    (Université de Paris, INSERM, IAME)

  • Roger Grand

    (Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT))

Abstract

The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with large spectrum activity against several RNA viruses in vitro and in small animal models. Here, we evaluate the antiviral activity of favipiravir against Zika or SARS-CoV-2 virus in cynomolgus macaques. In both models, high doses of favipiravir are initiated before infection and viral kinetics are evaluated during 7 to 15 days after infection. Favipiravir leads to a statistically significant reduction in plasma Zika viral load compared to untreated animals. However, favipiravir has no effects on SARS-CoV-2 viral kinetics, and 4 treated animals have to be euthanized due to rapid clinical deterioration, suggesting a potential role of favipiravir in disease worsening in SARS-CoV-2 infected animals. To summarize, favipiravir has an antiviral activity against Zika virus but not against SARS-CoV-2 infection in the cynomolgus macaque model. Our results support the clinical evaluation of favipiravir against Zika virus but they advocate against its use against SARS-CoV-2 infection.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32565-w
    DOI: 10.1038/s41467-022-32565-w
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    as
    1. 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.
    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.
    3. Romain Marlin & Veronique Godot & Sylvain Cardinaud & Mathilde Galhaut & Severin Coleon & Sandra Zurawski & Nathalie Dereuddre-Bosquet & Mariangela Cavarelli & Anne-Sophie Gallouët & Pauline Maisonnas, 2021. "Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    4. Ashleigh Shannon & Barbara Selisko & Nhung-Thi-Tuyet Le & Johanna Huchting & Franck Touret & Géraldine Piorkowski & Véronique Fattorini & François Ferron & Etienne Decroly & Chris Meier & Bruno Coutar, 2020. "Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
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