Identification of Lurasidone as a Potent Inhibitor of Severe Fever with Thrombocytopenia Syndrome Virus by Targeting the Viral Nucleoprotein

Ting Cheng¹Qingcui Xiao²Jing Cui²Shuangjie Dong²Yuqin Wu²Wenqiang Li²Xinya Yang²Lina Ma²Zhiyong Li^2,3,4*Peng Sun^2,3,4*Yinli Xie^2,3*

• ¹School of Basic Medical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou，Zhejiang, China
• ²School of Basic Medical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China
• ³Institute of Virology, Wenzhou Medical University, Wenzhou, Zhejiang, China
• ⁴Institute of Biology, Hebei Academy of Sciences, Shijiazhuang, Hebei, China

Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) is an emerging tick-borne virus that causes acute febrile hemorrhagic disease with thrombocytopenia in humans, resulting in a high mortality rate. Currently, there are no specific antiviral drugs approved for the prevention or treatment of SFTSV infections. The viral nucleoprotein (NP) is essential for the replication and transcription of the SFTSV genome. In this study, we screened potential drugs targeting the SFTSV NP from the FDA-approved drug library using AutoDock Vina molecular docking. We identified several compounds that can inhibit SFTSV infection, with lurasidone showing particularly strong antiviral activity. Lurasidone exhibited an IC 50 value of 4.552 µM and a selection index (SI) greater than 10, demonstrating a promising balance between antiviral efficacy and low cytotoxicity. Mechanistic studies reveal that lurasidone may exert its antiviral effects by binding to the viral NP and inhibiting genome replication. This study provides important theoretical basis for the development of novel antiviral drugs and may serve as a reference for therapeutic strategies against SFTSV.