8H7Z

Cryo-EM structure of SARS-CoV-2 BA.2 RBD in complex with BA7535 fab (local refinement)

Summary for 8H7Z

• Entry DOI: 10.2210/pdb8h7z/pdb
• EMDB information: 34526
• Descriptor: Spike glycoprotein, BA7535 fab (3 entities in total)
• Functional Keywords: viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 95551.30

Authors

Liu, Z.,Yan, A.,Gao, Y. (deposition date: 2022-10-21, release date: 2023-08-30, Last modification date: 2024-11-06)

Primary citation

Wang, Y.,Yan, A.,Song, D.,Duan, M.,Dong, C.,Chen, J.,Jiang, Z.,Gao, Y.,Rao, M.,Feng, J.,Zhang, Z.,Qi, R.,Ma, X.,Liu, H.,Yu, B.,Wang, Q.,Zong, M.,Jiao, J.,Xing, P.,Pan, R.,Li, D.,Xiao, J.,Sun, J.,Li, Y.,Zhang, L.,Shen, Z.,Sun, B.,Zhao, Y.,Zhang, L.,Dai, J.,Zhao, J.,Wang, L.,Dou, C.,Liu, Z.,Zhao, J.
Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.
Nat Commun, 15:842-842, 2024

PubMed Abstract: 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.

PubMed: 38287016
DOI: 10.1038/s41467-024-45050-3

Experimental method

ELECTRON MICROSCOPY (3.07 Å)