Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: dose-efficacy studies upon oral administration
BackgroundSevere fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a viral hemorrhagic fever with a high case fatality rate. Favipiravir was reported to be effective in the treatment of SFTSV infection in vivo in type I interferon receptor knockout (IFNAR-/-) mice at treatment dosages of both 60 mg/kg/day and 300 mg/kg/day for a duration of 5 days.\n\nMethodsIn this study, the efficacy of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day against SFTSV infection in an IFNAR-/- mouse infection model was investigated. IFNAR-/- mice were subcutaneously infected with SFTSV at a 1.0 x 106 50% tissue culture infectious dose followed by twice daily administration of favipiravir, comprising a total dose of either 120 mg/kg/day or 200 mg/kg/day. The treatment was initiated either immediately post infection or at predesignated time points post infection.\n\nResultsAll mice treated with favipiravir at dosages of 120 mg/kg/day or 200 mg/kg/day survived when the treatment was initiated at no later than 4 days post infection. A decrease in body weight of mice was observed when the treatment was initiated at 3-4 days post infection. Furthermore, all control mice died. The body weight of mice did not decrease when treatment with favipiravir was initiated immediately post infection at dosages of 120 mg/kg/day and 200 mg/kg/day.\n\nConclusionsSimilar to the literature-reported peritoneal administration of favipiravir at 300 mg/kg/day, the oral administration of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day to IFNAR-/- mice infected with SFTSV was effective.\n\nAuthor summarySevere fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a generalized infectious disease with a high case fatality rate. Currently, no effective therapeutics for SFTS is available; therefore, the development of effective antiviral drugs is needed. Favipiravir exhibits antiviral activity against various RNA viruses, including SFTSV. The present study demonstrated the efficacy of favipiravir in the treatment of SFTSV infection in a lethal mouse model, when the dose was set similar to that approved for anti-influenza drug in humans by the Ministry of Health, Labour and Welfare, Japan. The present study suggests that favipiravir is a promising drug for the treatment of SFTSV infection.