Harringtonine : A more effective antagonist for Omicron variant
Copyright © 2023. Published by Elsevier Inc..
Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 μM, while the IC50 in delta variant decreased to 0.101 μM, the IC50 in Omicron BA.1 variant was 0.042 μM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 μM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:213 |
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| Enthalten in: |
Biochemical pharmacology - 213(2023) vom: 15. Juli, Seite 115617 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Shiling [VerfasserIn] |
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| Links: |
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| Themen: |
Harringtonine |
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| Anmerkungen: |
Date Completed 19.06.2023 Date Revised 18.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bcp.2023.115617 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357136713 |
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| 100 | 1 | |a Hu, Shiling |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Harringtonine |b A more effective antagonist for Omicron variant |
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| 500 | |a Date Completed 19.06.2023 | ||
| 500 | |a Date Revised 18.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 μM, while the IC50 in delta variant decreased to 0.101 μM, the IC50 in Omicron BA.1 variant was 0.042 μM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 μM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Harringtonine | |
| 650 | 4 | |a Membrane fusion | |
| 650 | 4 | |a Omicron variant | |
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| 650 | 4 | |a Spike protein | |
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| 700 | 1 | |a Wang, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huajun |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 | |
| 700 | 1 | |a Jia, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuejin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shemin |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Tengchuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chiu, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a He, Langchong |e verfasserin |4 aut | |
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