Enhanced protection against experimental Junin virus infection through the use of a modified favipiravir loading dose strategy

- A modified favipiravir loading dose treatment strategy was evaluated against lethal JUNV infection in guinea pigs.
- Initiated 2 days post-JUNV challenge, the modified treatment regimen resulted in 100% survival.
- Treatment initiated 5 days post-JUNV infection slowed disease progression and reduced mortality by 50%.
- Continued development of favipiravir as an antiviral therapy for the treatment of severe arenaviral infections is warranted.

A collection of Old and New World arenaviruses are etiologic agents of viral hemorrhagic fever, a syndrome that features hematologic abnormalities, vascular leak, hypovolemia, and multi-organ failure. Treatment is limited to ribavirin for Lassa fever and immune plasma for Argentine hemorrhagic fever. Improved therapeutic options that are safe, more effective and widely available are needed. Here, we show that modification of favipiravir treatment to include a high-dose loading period achieves complete protection in a guinea pig model of Argentine hemorrhagic fever when treatment was initiated two days following challenge with Junin virus (JUNV). This loading dose strategy also protected 50% of animals from lethal disease when treatment was delayed until 5 days post-infection and extended the survival time in those that succumbed. Consistent with the survival data, dramatic reductions in serum and tissue virus loads were observed in animals treated with favipiravir. This is the first report demonstrating complete protection against uniformly lethal JUNV infection in guinea pigs by administration of a small molecule antiviral drug.