Li Shufen, Ye Meidi, Chen Yuanqiao, Zhang Yulan, Li Jiachen, Liu Wei, Li Hao, Peng Ke
State Key Laboratory of Virology, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Front Pharmacol. 2021 Nov 11;12:735223. doi: 10.3389/fphar.2021.735223. eCollection 2021.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying high anti-SFTSV efficacy, in which, toosendanin showed the highest inhibition potency. Mechanistic investigation indicated that toosendanin inhibited SFTSV infection at the step of virus internalization. The anti-viral effect of toosendanin against SFTSV was further verified in mouse infection models, and the treatment with toosendanin significantly reduced viral load and histopathological changes . The antiviral activity of toosendanin was further expanded to another bunyavirus and the emerging SARS-CoV-2. This study revealed a broad anti-viral effect of toosendanin and indicated its potential to be developed as an anti-viral drug for clinical use.
严重发热伴血小板减少综合征病毒（SFTSV）是一种新出现的蜱传病毒，可引发严重传染病，重症病例的病死率高达50%。目前，尚无获批用于治疗SFTSV感染的有效药物。在此，我们对一个天然提取物文库进行了高通量筛选，以寻找具有抗SFTSV感染活性的化合物。鉴定出三种活性化合物，三七皂苷Ft1、石榴皮苷和川楝素，它们表现出较高的抗SFTSV效力，其中川楝素的抑制效力最高。机制研究表明，川楝素在病毒内化步骤抑制SFTSV感染。川楝素对SFTSV的抗病毒作用在小鼠感染模型中得到进一步验证，用川楝素治疗可显著降低病毒载量和组织病理学变化。川楝素的抗病毒活性进一步扩展到另一种布尼亚病毒和新出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。本研究揭示了川楝素具有广泛的抗病毒作用，并表明其有开发成为临床用抗病毒药物的潜力。
