ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker
© 2021. The Author(s)..
The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Signal transduction and targeted therapy - 6(2021), 1 vom: 25. Aug., Seite 315 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Yuning [VerfasserIn] |
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| Links: |
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| Themen: |
ACE2 protein, human |
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| Anmerkungen: |
Date Completed 20.09.2021 Date Revised 07.12.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41392-021-00740-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329769626 |
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| 520 | |a © 2021. The Author(s). | ||
| 520 | |a The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2 | ||
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| 700 | 1 | |a Zhang, Ya-Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Renhong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhe-Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yaning |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Jianxia |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Wendi |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Zhijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yi-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ganjun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chunhe |e verfasserin |4 aut | |
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