Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 1 vom: 23. Jan., Seite 113653 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yanqun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2024 Date Revised 12.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.113653 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain |
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| 500 | |a Date Revised 12.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Yang, Minnan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Xinyi |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Qihong |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Peilan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Kexin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiantao |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhao, Xiaochu |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Juxue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Airu |e verfasserin |4 aut | |
| 700 | 1 | |a Gan, Mian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jingjun |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Ruoxi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuo, Jianfen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Haiyue |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Linling |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qingtao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yaoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Huibin |e verfasserin |4 aut | |
| 700 | 1 | |a So, Ray T Y |e verfasserin |4 aut | |
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| 700 | 1 | |a Wang, Xiangxi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
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