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Title | Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain. |
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Journal, issue, pages | Cell Rep, Vol. 43, Issue 1, Page 113653, Year 2024 |
Publish date | Jan 23, 2024 |
Authors | Yanqun Wang / Zhaoyong Zhang / Minnan Yang / Xinyi Xiong / Qihong Yan / Lei Cao / Peilan Wei / Yuting Zhang / Lu Zhang / Kexin Lv / Jiantao Chen / Xuesong Liu / Xiaochu Zhao / Juxue Xiao / Shengnan Zhang / Airu Zhu / Mian Gan / Jingjun Zhang / Ruoxi Cai / Jianfen Zhuo / Yanjun Zhang / Haiyue Rao / Bin Qu / Yuanyuan Zhang / Lei Chen / Jun Dai / Linling Cheng / Qingtao Hu / Yaoqing Chen / Huibin Lv / Ray T Y So / Malik Peiris / Jingxian Zhao / Xiaoqing Liu / Chris Ka Pun Mok / Xiangxi Wang / Jincun Zhao / |
PubMed Abstract | 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 ...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. |
External links | Cell Rep / PubMed:38175758 |
Methods | EM (single particle) |
Resolution | 3.0 - 3.5 Å |
Structure data | EMDB-37240, PDB-8khc: EMDB-37241, PDB-8khd: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / omicron / RBD / Fab |