Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito, Mutsuyo; Saijo, Masayuki

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), a novel bunyavirus classified into the genus Phlebovirus and family Bunyaviridae according to the previous nomenclature by the International Committee of Taxonomy of Viruses (ICTV). However, according to the nomenclature by the ICTV, SFTSV has been classified into the Genus Banyangvirus, Family Phenuiviridae and re-named as Huaiyangshan banyangvirus. In this review article, we have referred to it as "SFTSV." SFTSV is a negative-stranded RNA virus and its genome comprises of three segments, designated as large (L), medium (M), and small (S). The L and M segments encode the RNA dependent RNA polymerase (RdRp) and glycoprotein precursors (Gn and Gc), respectively, and S segment encodes nucleoprotein and nonstructural proteins. The RdRp of SFTSV is responsible for viral replication and is a major target of nucleoside analogs, which are used as therapeutic antiviral drugs. The Gn and Gc are presented on the surface of the virion and are the main targets of neutralizing antibodies. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in Hubei and Henan provinces in Central China (Yu et al., 2011) . Subsequently, the virus was isolated from sick patients in Japan and South Korea, indicating that SFTSV was endemic not only to China, but also to South Korea and Japan (Kim et al., 2013; Takahashi et al., 2014) . In addition, recent studies have reported SFTS as endemic to Vietnam (Tran et al., 2019) and Xinjiang, China (Zhu et al., 2019) , indicating that the distribution of SFTSV in Southeast Asia might be much more extensive than expected. Humans become infected mainly via tick-bites, but through close contact with animals such as cats, and dogs and human-to-human transmission has also been reported (Gai et al., 2012; Niu et al., 2013; Kida et al., 2019) . The case fatality rate of SFTS is found to vary between 6 and 30% in Japan and South Korea, with a fatality rate of approximately 30% (Choi et al., 2016; Kato et al., 2016) . Although World Health Organization listed SFTS as a disease requiring urgent research and development (World Health Organization, 2017) , there is no available effective SFTS treatment.