Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
2024-01-23
发表期刊CELL REPORTS (IF:7.5[JCR-2023],8.5[5-Year])
ISSN2211-1247
卷号43期号:1
发表状态已发表
DOI10.1016/j.celrep.2023.113653
摘要

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 (cryoEM) 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.

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收录类别SCI
语种英语
资助项目National Key R&D Program of China[2023YFC3041600] ; National Natural Science Foundation of China[
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:001154909100001
出版者CELL PRESS
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349917
专题免疫化学研究所
生命科学与技术学院_博士生
免疫化学研究所_特聘教授组_赵金存组
通讯作者Wang, Yanqun; Liu, Xiaoqing; Mok, Chris Ka Pun; Wang, Xiangxi; Zhao, Jincun
作者单位
1.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou 510120, Guangdong, Peoples R China
2.Guangzhou Med Univ, GMU GIBH Joint Sch Life Sci, Guangzhou, Guangdong, Peoples R China
3.Guangzhou Med Univ, Clin Lab Med Dept, Affiliated Hosp 2, Guangzhou, Peoples R China
4.Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Natl Lab Macromol, Beijing, Peoples R China
5.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Guangzhou Natl Lab, Guangzhou, Peoples R China
7.Guangzhou Customs Dist Technol Ctr, Hlth & Quarantine Lab, Guangzhou, Peoples R China
8.Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen, Peoples R China
9.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, Dept Crit Care Med,Affiliated Hosp 1,State Key Lab, Guangzhou, Peoples R China
10.Capital Med Univ, Sch Basic Med Sci, Beijing, Peoples R China
11.Univ Hong Kong, Li Ka Shing Fac Med, Sch Publ Hlth, HKU Pasteur Res Pole, Hong Kong, Peoples R China
12.Univ Hong Kong, Sch Publ Hlth, Hong Kong, Peoples R China
13.Chinese Univ Hong Kong, Jockey Club Sch Publ Hlth & Primary Care, Hong Kong, Peoples R China
14.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Fac Med, Hong Kong, Peoples R China
15.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Sch Med ,Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China
16.Chinese Univ Hong Kong, SH Ho Res Ctr Infect Dis, Hong Kong, Peoples R China
通讯作者单位免疫化学研究所
推荐引用方式
GB/T 7714
Wang, Yanqun,Zhang, Zhaoyong,Yang, Minnan,et al. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain[J]. CELL REPORTS,2024,43(1).
APA Wang, Yanqun.,Zhang, Zhaoyong.,Yang, Minnan.,Xiong, Xinyi.,Yan, Qihong.,...&Zhao, Jincun.(2024).Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.CELL REPORTS,43(1).
MLA Wang, Yanqun,et al."Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain".CELL REPORTS 43.1(2024).
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