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

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

doi:10.3390/v13102047

Abstract

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.

Highlights

Members of the order Bunyavirales are a group of enveloped RNA viruses with segmented, single-stranded, negative-sense or ambisense RNA genomes [1]
We identified a number of drug compounds that inhibited Severe fever with thrombocytopenia syndrome virus (SFTSV) replication at low micromolar concentrations, including hexachlorophene, which likely targets the SFTSV glycoprotein C (Gc) glycoprotein [14]
Viral load reduction assay was performed to evaluate the antiviral activity of synthesized peptide against SFTSV as we described previously [14]

Summary

Introduction

Members of the order Bunyavirales are a group of enveloped RNA viruses with segmented, single-stranded, negative-sense or ambisense RNA genomes [1]. Bunyaviruses that cause life-threatening viral hemorrhagic fever include severe fever with thrombocytopenia syndrome virus (SFTSV), Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHFV), and hantaviruses. The L segment encodes the RNAdependent RNA polymerase (RdRp), which mediates viral RNA replication and synthesis. The M segment encodes the viral envelope glycoproteins, glycoprotein N (Gn), and glycoprotein C (Gc), which mediate fusion between the viral and host cell membranes. The S segment encodes the viral nucleoprotein (NP) and the nonstructural protein (NSs). NP is the most abundantly expressed protein in SFTSV viral particles and infected cells. Another report showed that glucosylceramide, the glucose-modified lipid, is required for efficient SFTSV entry into human bone osteosarcoma epithelial (U2OS) cells [6]

Methods

Results

Conclusion