In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn

Yuan, Shuo-Feng; Wen, Lei; Chik, Kenn Ka-Heng; Du, Jiang; Ye, Zi-Wei; Cao, Jian-Li; Tang, Kai-Ming; Liang, Rong-Hui; Cai, Jian-Piao; Luo, Cui-Ting; Yin, Fei-Fei; Lu, Gang; Chu, Hin; Liang, Mi-Fang; Jin, Dong-Yan; Yuen, Kwok-Yung; Chan, Jasper Fuk-Woo

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses.