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Nat Commun
. 2024 Jan 2;15(1):162.
doi: 10.1038/s41467-023-44504-4. Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1
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
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.
. 2024 Jan 2;15(1):162.
doi: 10.1038/s41467-023-44504-4. Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1
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
- PMID: 38167417
- PMCID: PMC10762260
- DOI: 10.1038/s41467-023-44504-4
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.