8H7L

Cryo-EM Structure of SARS-CoV-2 BA.2 Spike protein in complex with BA7535

8H7L の概要

• エントリーDOI: 10.2210/pdb8h7l/pdb
• EMDBエントリー: 34522
• 分子名称: Spike glycoprotein, BA7535 fab heavt chain, BA7535 fab light chain, ... (5 entities in total)
• 機能のキーワード: sars-cov-2 ba.2, spike, fab, cryo-em, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 601217.58

構造登録者

Liu, Z.,Yan, A.,Gao, Y. (登録日: 2022-10-20, 公開日: 2023-08-30, 最終更新日: 2025-06-18)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.44 Å)