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

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文献类型：外文期刊

作者： Khan, Ilyas ¹ ; Li, Sunan ¹ ; Tao, Lihong ¹ ; Wang, Chong ¹ ; Ye, Bowei ² ; Li, Huiyu ² ; Liu, Xiaoyang ¹ ; Ahmad, Iqbal ¹ ; Su, Wenqiang ¹ ; Zhong, Gongxun ¹ ; Wen, Zhiyuan ¹ ; Wang, Jinliang ¹ ; Hua, Rong-Hong ¹ ; Ma, Ao ² ; Liang, Jie ² ; Wan, Xiao-Peng ¹ ; Bu, Zhi-Gao ¹ ; Zheng, Yong-Hui ³ ;

作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Harbin, Peoples R China

2.Univ Illinois, Ctr Bioinformat & Quantitat Biol, Richard & Loan Hill Dept Biomed Engn, Chicago, IL 60607 USA

3.Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA

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

ISSN：

年卷期： 2024 年 15 卷 1 期

页码：

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

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