tetano
Editor, Senior Moderator
Cell Rep
. 2024 Jan 3;43(1):113653.
doi: 10.1016/j.celrep.2023.113653. Online ahead of print. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
Yanqun Wang[SUP] 1 [/SUP], Zhaoyong Zhang[SUP] 2 [/SUP], Minnan Yang[SUP] 3 [/SUP], Xinyi Xiong[SUP] 4 [/SUP], Qihong Yan[SUP] 2 [/SUP], Lei Cao[SUP] 3 [/SUP], Peilan Wei[SUP] 5 [/SUP], Yuting Zhang[SUP] 2 [/SUP], Lu Zhang[SUP] 6 [/SUP], Kexin Lv[SUP] 7 [/SUP], Jiantao Chen[SUP] 2 [/SUP], Xuesong Liu[SUP] 8 [/SUP], Xiaochu Zhao[SUP] 9 [/SUP], Juxue Xiao[SUP] 2 [/SUP], Shengnan Zhang[SUP] 2 [/SUP], Airu Zhu[SUP] 2 [/SUP], Mian Gan[SUP] 2 [/SUP], Jingjun Zhang[SUP] 2 [/SUP], Ruoxi Cai[SUP] 2 [/SUP], Jianfen Zhuo[SUP] 2 [/SUP], Yanjun Zhang[SUP] 2 [/SUP], Haiyue Rao[SUP] 2 [/SUP], Bin Qu[SUP] 4 [/SUP], Yuanyuan Zhang[SUP] 2 [/SUP], Lei Chen[SUP] 2 [/SUP], Jun Dai[SUP] 6 [/SUP], Linling Cheng[SUP] 2 [/SUP], Qingtao Hu[SUP] 2 [/SUP], Yaoqing Chen[SUP] 7 [/SUP], Huibin Lv[SUP] 10 [/SUP], Ray T Y So[SUP] 11 [/SUP], Malik Peiris[SUP] 12 [/SUP], Jingxian Zhao[SUP] 5 [/SUP], Xiaoqing Liu[SUP] 13 [/SUP], Chris Ka Pun Mok[SUP] 14 [/SUP], Xiangxi Wang[SUP] 15 [/SUP], Jincun Zhao[SUP] 16 [/SUP]
Affiliations
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.
Keywords: CP: Immunology; conserved epitope; in vivo; mouse model; neutralizing antibody; receptor binding domain; sarbecovirus.
. 2024 Jan 3;43(1):113653.
doi: 10.1016/j.celrep.2023.113653. Online ahead of print. Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain
Yanqun Wang[SUP] 1 [/SUP], Zhaoyong Zhang[SUP] 2 [/SUP], Minnan Yang[SUP] 3 [/SUP], Xinyi Xiong[SUP] 4 [/SUP], Qihong Yan[SUP] 2 [/SUP], Lei Cao[SUP] 3 [/SUP], Peilan Wei[SUP] 5 [/SUP], Yuting Zhang[SUP] 2 [/SUP], Lu Zhang[SUP] 6 [/SUP], Kexin Lv[SUP] 7 [/SUP], Jiantao Chen[SUP] 2 [/SUP], Xuesong Liu[SUP] 8 [/SUP], Xiaochu Zhao[SUP] 9 [/SUP], Juxue Xiao[SUP] 2 [/SUP], Shengnan Zhang[SUP] 2 [/SUP], Airu Zhu[SUP] 2 [/SUP], Mian Gan[SUP] 2 [/SUP], Jingjun Zhang[SUP] 2 [/SUP], Ruoxi Cai[SUP] 2 [/SUP], Jianfen Zhuo[SUP] 2 [/SUP], Yanjun Zhang[SUP] 2 [/SUP], Haiyue Rao[SUP] 2 [/SUP], Bin Qu[SUP] 4 [/SUP], Yuanyuan Zhang[SUP] 2 [/SUP], Lei Chen[SUP] 2 [/SUP], Jun Dai[SUP] 6 [/SUP], Linling Cheng[SUP] 2 [/SUP], Qingtao Hu[SUP] 2 [/SUP], Yaoqing Chen[SUP] 7 [/SUP], Huibin Lv[SUP] 10 [/SUP], Ray T Y So[SUP] 11 [/SUP], Malik Peiris[SUP] 12 [/SUP], Jingxian Zhao[SUP] 5 [/SUP], Xiaoqing Liu[SUP] 13 [/SUP], Chris Ka Pun Mok[SUP] 14 [/SUP], Xiangxi Wang[SUP] 15 [/SUP], Jincun Zhao[SUP] 16 [/SUP]
Affiliations
- PMID: 38175758
- DOI: 10.1016/j.celrep.2023.113653
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.
Keywords: CP: Immunology; conserved epitope; in vivo; mouse model; neutralizing antibody; receptor binding domain; sarbecovirus.