Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: Dose-efficacy studies upon oral administration

• Published in: PloS one Vol. 13; no. 10; p. e0206416
• Main Authors: Tani, Hideki, Komeno, Takashi, Fukuma, Aiko, Fukushi, Shuetsu, Taniguchi, Satoshi, Shimojima, Masayuki, Uda, Akihiko, Morikawa, Shigeru, Nakajima, Nozomi, Furuta, Yousuke, Saijo, Masayuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.10.2018; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Amides - administration & dosage; Amides - pharmacology; Amides - therapeutic use; Analysis; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antiviral agents; Biology and Life Sciences; Body weight; Cercopithecus aethiops; Disease Models, Animal; Dose-response relationship (Biochemistry); Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Ebola virus; Fatalities; Fever; Hemorrhage; Hemorrhagic fever; Infections; Infectious diseases; Influenza; Interferon; Laboratories; Medicine and Health Sciences; Mice; Mortality; Neutralizing; Oral administration; People and Places; Peritoneum; Phlebotomus Fever - drug therapy; Phlebovirus - drug effects; Phlebovirus - immunology; Phlebovirus - physiology; Pyrazines - administration & dosage; Pyrazines - pharmacology; Pyrazines - therapeutic use; Research and Analysis Methods; RNA polymerase; Rodents; Thrombocytopenia; Tissue culture; Vero Cells; Virology; Viruses; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0206416

Severe 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. In 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 × 10(6) 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. Neutralizing antibodies in the convalescent-phase mouse sera was examined by the pseudotyped VSV system. All 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. Neutralizing antibodies were detected in the convalescent-phase mouse sera. Similar 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.