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Favipiravir and severe acute respiratory syndrome coronavirus 2 in hamster model
Jean-Sélim Driouich; Maxime Cochin; Guillaume Lingas; Grégory Moureau; Franck Touret; Paul-Rémi Petit; Géraldine Piorkowski; Karine Barthélémy; Bruno Coutard; Jérémie Guedj; Xavier de Lamballerie; Caroline Solas; Antoine Nougairède.
Affiliation
  • Jean-Sélim Driouich; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Maxime Cochin; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Guillaume Lingas; Université de Paris, IAME, INSERM, F-75018 Paris, France
  • Grégory Moureau; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Franck Touret; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Paul-Rémi Petit; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Géraldine Piorkowski; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Karine Barthélémy; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Bruno Coutard; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Jérémie Guedj; Université de Paris, IAME, INSERM, F-75018 Paris, France
  • Xavier de Lamballerie; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
  • Caroline Solas; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France ; Laboratoire de Pharmacocinétique et Toxicologie, Hôpital La Timone
  • Antoine Nougairède; Unité des Virus Émergents, UVE: Aix Marseille Univ, IRD 190, INSERM 1207, Marseille, France
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-191775
ABSTRACT
Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we used a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment was initiated before or simultaneously to infection, favipiravir had a strong dose effect, leading to dramatic reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlated with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. The antiviral efficacy observed in this study was achieved with plasma drug exposure comparable with those previously found during human clinical trials and was associated with weight losses in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.
License
cc_by_nc_nd
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Document type: Preprint
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Document type: Preprint