Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 02. Jan., Seite 162 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khan, Ilyas [VerfasserIn] |
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| Links: |
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| Themen: |
Intracellular Signaling Peptides and Proteins |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 05.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-44504-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366580469 |
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| 520 | |a 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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| 700 | 1 | |a Li, Sunan |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chong |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Bowei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Huiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmad, Iqbal |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Wenqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Gongxun |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Zhiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jinliang |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Rong-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ao |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Xiao-Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Bu, Zhi-Gao |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yong-Hui |e verfasserin |4 aut | |
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