Intracellular conversion and in vivo dose response of favipiravir (T-705) in rodents infected with Ebola virus

During the 2013–2016 Ebola virus (EBOV) outbreak in West Africa, our team at USAMRIID evaluated the antiviral activity of a number of compounds, including favipiravir (T-705), in vitro and in mouse and nonhuman primate (NHP) models of Ebola virus disease. In this short communication, we present our findings for favipiravir in cell culture and in mice, while an accompanying paper presents the results of NHP studies. We confirmed previous reports that favipiravir has anti-EBOV activity in mice. Additionally, we found that the active form of favipiravir is generated in mice in tissues relevant for the pathogenesis of EBOV infection. Finally, we observed that protection can be achieved in mice down to 8 mg/kg/day, which is lower than the dosing regimens previously reported. An accompanying paper reports the results of treating nonhuman primates infected with EBOV or with Marburg virus with oral or intravenous favipiravir. •Early in the course of the West African Ebola epidemic, we evaluated the activity of favipiravir in vitro and in mice.•Favipiravir-RTP, the active form of the compound, was generated in vitro and in vivo.•Full protection in mice was observed at a wide range of doses in once- and twice-daily dosing regimens.•The protective dose of favipiravir in mice was found to be between 8 mg/kg/day and 1.6 mg/kg/day.