2. Academic Validation
  3. Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1

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

  • Nat Commun. 2024 Jan 2;15(1):162. doi: 10.1038/s41467-023-44504-4.
Ilyas Khan 1,  Sunan Li 1,  Lihong Tao 1,  Chong Wang 1,  Bowei Ye 2,  Huiyu Li 2,  Xiaoyang Liu 1,  Iqbal Ahmad 1,  Wenqiang Su 1,  Gongxun Zhong 1,  Zhiyuan Wen 1,  Jinliang Wang 1,  Rong-Hong Hua 1,  Ao Ma 2,  Jie Liang 2,  Xiao-Peng Wan 3,  Zhi-Gao Bu 4,  Yong-Hui Zheng 5
Affiliations

Affiliations

  • 1 State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
  • 2 Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, 60607, USA.
  • 3 State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China. wanxiaopeng@caas.cn.
  • 4 State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China. buzhigao@caas.cn.
  • 5 Department of Microbiology and Immunology, The University of Illinois Chicago, Chicago, IL, 60612, USA. zhengyh@uic.edu.
PMID: 38167417 DOI: 10.1038/s41467-023-44504-4
Abstract

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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