Preclinical efficacy of a favipiravir and nitazoxanide combination against Rift Valley Fever Virus
Emerging and re-emerging viruses represent a major global health challenge. To address this, the WHO encourages the development of broad-spectrum medical countermeasures. This study evaluated the efficacy of repurposed broad-spectrum molecules against Bunyaviricetes viruses and more specifically Rift Valley fever virus (RVFV). In vitro, favipiravir and nitazoxanide showed low effective doses with an additive effect in combination against several viruses, including RVFV, Crimean-Congo hemorrhagic fever virus and Hantaan virus. In a murine model of severe RVFV infection, combination treatment reduced viral replication and increased time to death. Pharmacokinetic analyses revealed favorable inhibitory quotients for favipiravir, whereas nitazoxanide displayed low exposure in mice. Favipiravir-induced viral mutagenesis was confirmed, and nitazoxanide targeted late replication steps. Additionally, no resistant variants emerged after serial passages in vitro. Despite the need for further studies in other animal models, these findings underscore the potential of this broad-spectrum compound combination against RVFV and other Bunyaviricetes viruses.
Authors
- Gilda Grard (ORCID: https://orcid.org/0000-0002-6088-2581)
- Guillaume Lingas (ORCID: https://orcid.org/0000-0001-8566-6220)
- Madeleine Giocanti
- Boris Pastorino (ORCID: https://orcid.org/0000-0001-5233-5193)
- Jean‐Sélim Driouich (ORCID: https://orcid.org/0000-0003-2326-2938)
- Clément Diarra
- Rayane Amaral
- Caroline Solas
- Franck Touret (ORCID: https://orcid.org/0000-0002-4734-2249)
- Jérémie Guedj (ORCID: https://orcid.org/0000-0002-5534-5482)
- Stéphane Mély (ORCID: https://orcid.org/0000-0002-3278-3455)
- Nadège Néant
- Sarah Chaput (ORCID: https://orcid.org/0000-0002-4283-0040)
- Antoine Nougairède
- Pauline Darbon
- Géraldine Piorkowski
- Xavier de Lamballerie
Institutions
- Inserm (FR)
- Université Paris Cité (FR)
- Aix-Marseille Université (FR)
- Sorbonne Paris Cité (FR)
- Le Laboratoire P4 Inserm Jean Mérieux (FR)
- Institut de Médecine Tropicale du Service de Santé des Armées (FR)
- Hôpital de la Timone (FR)
- Institut de Recherche pour le Développement (FR)
Publication Details
- Journal
- Antiviral Research
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1016/j.antiviral.2026.106402
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Aix-Marseille Université
- Institut National de la Santé et de la Recherche Médicale
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Association Neurofibromatoses et Recklinghause
- Agence de l'innovation de Défense