tetano
Editor, Senior Moderator
Nat Commun
. 2024 Jan 29;15(1):842.
doi: 10.1038/s41467-024-45050-3. Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants
Yanqun Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], An Yan[SUP] #[/SUP][SUP] 4 [/SUP], Deyong Song[SUP] #[/SUP][SUP] 5 [/SUP], Maoqin Duan[SUP] #[/SUP][SUP] 6 [/SUP], Chuangchuang Dong[SUP] 5 [/SUP], Jiantao Chen[SUP] 1 [/SUP], Zihe Jiang[SUP] 4 [/SUP], Yuanzhu Gao[SUP] 4 [/SUP], Muding Rao[SUP] 5 [/SUP], Jianxia Feng[SUP] 5 [/SUP], Zhaoyong Zhang[SUP] 1 [/SUP], Ruxi Qi[SUP] 4 [/SUP], Xiaomin Ma[SUP] 4 [/SUP], Hong Liu[SUP] 5 [/SUP], Beibei Yu[SUP] 5 [/SUP], Qiaoping Wang[SUP] 5 [/SUP], Mengqi Zong[SUP] 5 [/SUP], Jie Jiao[SUP] 5 [/SUP], Pingping Xing[SUP] 5 [/SUP], Rongrong Pan[SUP] 5 [/SUP], Dan Li[SUP] 5 [/SUP], Juxue Xiao[SUP] 1 [/SUP], Junbo Sun[SUP] 5 [/SUP], Ying Li[SUP] 5 [/SUP], Linfeng Zhang[SUP] 5 [/SUP], Zhenduo Shen[SUP] 5 [/SUP], Baiping Sun[SUP] 5 [/SUP], Yanyan Zhao[SUP] 5 [/SUP], Lu Zhang[SUP] 7 [/SUP], Jun Dai[SUP] 7 [/SUP], Jingxian Zhao[SUP] 1 [/SUP], Lan Wang[SUP] 8 [/SUP], Changlin Dou[SUP] 9 [/SUP], Zheng Liu[SUP] 10 [/SUP], Jincun Zhao[SUP] 11 12 13 14 [/SUP]
Affiliations
The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.
. 2024 Jan 29;15(1):842.
doi: 10.1038/s41467-024-45050-3. Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants
Yanqun Wang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], An Yan[SUP] #[/SUP][SUP] 4 [/SUP], Deyong Song[SUP] #[/SUP][SUP] 5 [/SUP], Maoqin Duan[SUP] #[/SUP][SUP] 6 [/SUP], Chuangchuang Dong[SUP] 5 [/SUP], Jiantao Chen[SUP] 1 [/SUP], Zihe Jiang[SUP] 4 [/SUP], Yuanzhu Gao[SUP] 4 [/SUP], Muding Rao[SUP] 5 [/SUP], Jianxia Feng[SUP] 5 [/SUP], Zhaoyong Zhang[SUP] 1 [/SUP], Ruxi Qi[SUP] 4 [/SUP], Xiaomin Ma[SUP] 4 [/SUP], Hong Liu[SUP] 5 [/SUP], Beibei Yu[SUP] 5 [/SUP], Qiaoping Wang[SUP] 5 [/SUP], Mengqi Zong[SUP] 5 [/SUP], Jie Jiao[SUP] 5 [/SUP], Pingping Xing[SUP] 5 [/SUP], Rongrong Pan[SUP] 5 [/SUP], Dan Li[SUP] 5 [/SUP], Juxue Xiao[SUP] 1 [/SUP], Junbo Sun[SUP] 5 [/SUP], Ying Li[SUP] 5 [/SUP], Linfeng Zhang[SUP] 5 [/SUP], Zhenduo Shen[SUP] 5 [/SUP], Baiping Sun[SUP] 5 [/SUP], Yanyan Zhao[SUP] 5 [/SUP], Lu Zhang[SUP] 7 [/SUP], Jun Dai[SUP] 7 [/SUP], Jingxian Zhao[SUP] 1 [/SUP], Lan Wang[SUP] 8 [/SUP], Changlin Dou[SUP] 9 [/SUP], Zheng Liu[SUP] 10 [/SUP], Jincun Zhao[SUP] 11 12 13 14 [/SUP]
Affiliations
- PMID: 38287016
- PMCID: PMC10825162
- DOI: 10.1038/s41467-024-45050-3
The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.