Effectiveness of lignans against severe fever with thrombocytopenia syndrome virus infection.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes a life-threatening infectious disease with high mortality. Currently, there are no approved vaccines or specific therapeutic drugs for clinical use against SFTSV infection. Here, we screened a lignan compound library to identify candidates with anti-SFTSV activity. Two type I arylnaphthalide lignan lactones, Pronaphthalide A and Procumbenoside I, were identified as potent inhibitors of SFTSV infection. Mechanistic investigations indicated that these lignans exert their inhibitory effects at the viral binding and internalization stages. Molecular docking analysis revealed that these lignans can bind to the conserved B domain of the SFTSV glycoprotein Gn, an interaction validated by subsequent experiments as the core mechanism underlying their antiviral activity. In a mouse model of lethal SFTSV infection, treatment with these compounds, particularly Procumbenoside I, significantly inhibited viral infection, attenuated histopathological abnormalities, and improved survival rates. The antiviral activity of these lignans was further expanded to other bunyaviruses, including Lymphocytic choriomeningitis virus (LCMV) and Wetland virus (WELV). These findings uncover the broad-spectrum antiviral activity of type I arylnaphthalide lignans and support their potential as candidate therapeutic agents for the clinical intervention of bunyavirus infections.