Antiviral Activity of Favipiravir (T-705) Against Lethal Rift Valley Fever Virus Infection in Hamsters

Rift Valley fever (RVF) is a severe disease affecting both humans and a number of agriculturally important livestock species. The causative agent, RVF virus (RVFV), is primarily transmitted through mosquito bites, with transmission also occurring by exposure to infectious aerosols and direct contact with infected body fluids such as blood. Presently, there are no licensed vaccines or medicines to prevent or treat severe RVFV infection in humans. Favipiravir (T-705) is a novel compound licensed for the treatment of influenza in Japan and presently in Phase III clinical trials in the US, which has demonstrated favorable activity against an attenuated strain of RVFV, as well as other related viruses in cell culture. Additionally, it has also demonstrated favorable activity in mouse and hamster models based on infection with the closely related, less biohazardous Punta Toro virus. Although mouse models have been used extensively in RVFV research and are fairly well characterized, details regarding RVFV infection in hamsters are lacking. The present studies were aimed at characterizing RVFV infection in hamsters to gain a better understanding of the disease model compared to human disease, and employing the hamster infection model to evaluate T-705 as a promising broadly active antiviral with potential for off-label use to treat severe RVF disease. Herein, we describe the natural history of disease in hamsters challenged with low infectious doses of RVFV and demonstrate the efficacy of T-705 in preventing mortality and reducing viral loads in infected hamsters. Our results support the future use of the RVFV hamster infection model for early stage antiviral drug and vaccine development studies, as well as further development of T-705 using more advanced nonhuman primate models of disease