Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito, Mutsuyo; Saijo, Masayuki

2 ′ -Fluoro-2 ′ -deoxycytidine 2 ′ -Fluoro-2 ′ -deoxycytidine (2 ′ -FdC) is a nucleoside inhibitor used in anticancer drugs. It inhibits various RNA and DNA viruses in vitro, such as Borna virus (Bajramovic et al., 2004) , Lassa virus (Welch et al., 2016) , Crimean-Congo hemorrhagic fever virus (Welch et al., 2017) , influenza virus (Kumaki et al., 2011) , and herpesviruses (Wohlrab et al., 1985) . Smee et al. (2018) has shown the antiviral activity of 2 ′ -FdC against various bunyaviruses, such as La Crosse virus, Maporal virus, Punta Toro virus, Rift Valley fever virus, San Angelo virus, Heartland virus, and SFTSV. The IC 90 of 2 ′ -FdC against SFTSV was 3.7 µM in an in vitro assay ( Table 1) . This value was much lower than that of ribavirin (49.7 µM) in the same study and favipiravir (22 µM) in the study conducted by Tani et al. (2016) . In an in vivo study using IFNAR −/− mice, a 100 mg/kg/day treatment with 2 ′ -FdC was 100% protective against death caused by SFTSV (Table 2) . However, all the mice treated with 2 ′ -FdC experienced substantial weight loss after SFTSV inoculation, whereas the favipiravir-treated mice displayed very little weight loss, suggesting that favipiravir was more effective than 2 ′ -FdC in controlling morbidity during the infection (Smee et al., 2018) . It was also found that treatments with 100 mg/kg/day of either 2 ′ -FdC or favipiravir significantly reduced the viral titers in the serum. Furthermore, there was a slight discrepancy both in the survival rates and virus titers between mice treated with 100 mg/kg/day of 2 ′ -FdC and those with 200 mg/kg/day of 2 ′ -FdC. The survival rate was 80 vs. 100% for 200-and 100-mg/kg/day treatments, respectively; and the virus titer in the serum of 200 mg/kg/day-treated mice was higher than that of mice receiving the 100-mg/kg/day treatment. It was speculated that this was caused by the limited sample size (n = 4 or 5).