Citation: Jun Huang, Jinpeng Lv, Xiaojie Zheng, Junjun Jiang, Wei Liu, Shuchen Liu, Hao Liang, Hao Li. Effectiveness of lignans against severe fever with thrombocytopenia syndrome virus infection .VIROLOGICA SINICA, 2026, 41(4) : 912-922.  http://dx.doi.org/10.1016/j.virs.2026.07.003

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.

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    Effectiveness of lignans against severe fever with thrombocytopenia syndrome virus infection

      Corresponding author: Wei Liu, lwbime@163.com
      Corresponding author: Shuchen Liu, liusc118@163.com
      Corresponding author: Hao Liang, lianghao@gxmu.edu.cn
      Corresponding author: Hao Li, lihao_1986@126.com
    • a. Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, School of Public Health, Guangxi Medical University, Nanning 530021, China;
    • b. State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China;
    • c. Guangxi Engineering Center for Organoids and Organ-on-chips of Highly Pathogenic Microbial Infections & Biosafety III Laboratory, Life Science Institute, Guangxi Medical University, Nanning 530021, China;
    • d. Academy of Military Medical Sciences, Beijing 100850, China

    Abstract: 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.

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