Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion
Abstract Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein’s autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 01. Feb. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Shiling [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.01.22.477323 |
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| PPN (Katalog-ID): |
XBI035070781 |
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| 520 | |a Abstract Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein’s autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19. | ||
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| 700 | 1 | |a Ding, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Weina |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xinghai |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Yanni |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Zhuoyin |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Haoyun |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a He, Huaizhen |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Shengli |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Yingzhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Guanqun |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Zengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongjing |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jiayu |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Jiapan |e verfasserin |4 aut | |
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| 700 | 1 | |a Wang, Hongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shemin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huajun |e verfasserin |4 aut | |
| 700 | 1 | |a He, Langchong |e verfasserin |4 aut | |
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