Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1

文献类型： 外文期刊

第一作者： Khan, Ilyas

作者： Khan, Ilyas;Li, Sunan;Tao, Lihong;Wang, Chong;Liu, Xiaoyang;Ahmad, Iqbal;Su, Wenqiang;Zhong, Gongxun;Wen, Zhiyuan;Wang, Jinliang;Hua, Rong-Hong;Wan, Xiao-Peng;Bu, Zhi-Gao;Ye, Bowei;Li, Huiyu;Ma, Ao;Liang, Jie;Zheng, Yong-Hui

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期刊名称：NATURE COMMUNICATIONS （ 影响因子：16.6； 五年影响因子：17.0 ）

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年卷期： 2024 年 15 卷 1 期

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收录情况： SCI

摘要： SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides' antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses.

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