Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2.
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2.
复制标题
小分子化合物库的筛选确定川楝素是布尼亚病毒和 SARS-CoV-2 的抑制剂
DOI：
10.3389/fphar.2021.735223
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发表时间：
2021
影响因子：
5.6
通讯作者：
Peng K
中科院分区：
文献类型：
--
作者：
Li S;Ye M;Chen Y;Zhang Y;Li J;Liu W;Li H;Peng K
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，可引起严重的传染病，重症病例的病死率高达50%。目前，还没有有效的药物被批准用于治疗SFTSV感染。在这里，我们进行了高通量筛选的天然提取物库的化合物与抗SFTSV感染的活动。结果表明，三种化合物具有较高的抗SFTSV活性，其中川楝素的抑制活性最高，分别为三七Ft 1、石榴苷和川楝素。机理研究表明川楝素抑制SFTSV感染的作用可能是通过病毒内化的途径实现的。在小鼠感染模型中进一步验证了川楝素对SFTSV的抗病毒作用，并且用川楝素治疗显著降低了体内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SARS-CoV-2。本研究揭示了川楝素广泛的抗病毒作用，并表明其有潜力被开发为临床使用的抗病毒药物。
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 in vivo. 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.
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DOI：
10.3390/molecules25214878
发表时间：
2020-10-22
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Mohan S;Elhassan Taha MM;Makeen HA;Alhazmi HA;Al Bratty M;Sultana S;Ahsan W;Najmi A;Khalid A
通讯作者：
Khalid A
影响因子：
2.7
作者：
Hensel, Andreas;Bauer, Rudolf;Kraft, Karin
通讯作者：
Kraft, Karin
影响因子：
5.6
作者：
Jin, Young-Hee;Kwon, Sunoh;Ma, Jin Yeul
通讯作者：
Ma, Jin Yeul
DOI：
10.1038/nrd.2017.162
发表时间：
2018-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Kaufmann SHE;Dorhoi A;Hotchkiss RS;Bartenschlager R
通讯作者：
Bartenschlager R
影响因子：
14.2
作者：
Jung, I. Y.;Choi, W.;Kim, Y. K.
通讯作者：
Kim, Y. K.