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

Romain Marlin (1, 2) , Delphine Desjardins (1, 2) , Vanessa Contreras (1, 2) , Guillaume Lingas (3) , Caroline Solas (4) , Pierre Roques (1, 2) , Thibaut Naninck (1, 2) , Quentin Pascal (1, 2) , Sylvie Behillil (5) , Pauline Maisonnasse (1, 2) , Julien Lemaitre (1, 2) , Nidhal Kahlaoui (2, 1) , Benoit Delache (2, 1) , Andrés Pizzorno (6) , Antoine Nougairede (4) , Camille Ludot (2, 1) , Olivier Terrier (6) , Nathalie Dereuddre-Bosquet (1, 2) , Francis Relouzat (2, 1) , Catherine Chapon (2, 1) , Raphael Ho Tsong Fang (2, 1) , Sylvie van der Werf (5, 7) , Manuel Rosa Calatrava (6) , Denis Malvy (8, 9) , Xavier de Lamballerie (4) , Jeremie Guedj (3) , Roger Le Grand (1, 2)

1 IDMIT - Infectious Diseases Models for Innovative Therapies
2 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 UVE - Unité des Virus Emergents
5 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
6 CIRI - Centre International de Recherche en Infectiologie
7 CNR - laboratoire coordonnateur - Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris]
8 BPH - Bordeaux population health
9 GHiGS - Global Health in the Global South

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.

Domaines: Maladies infectieuses; Maladies émergentes; Virologie; Pharmacologie

Romain Marlin, Delphine Desjardins, Vanessa Contreras, Guillaume Lingas, Caroline Solas, et al.. Antiviral efficacy of favipiravir against Zika and SARS-CoV-2 viruses in non-human primates. Nature Communications, 2022, 13 (1), pp.5108. ⟨10.1038/s41467-022-32565-w⟩. ⟨hal-03797958⟩