7WS4

Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

7WS4 の概要

• エントリーDOI: 10.2210/pdb7ws4/pdb
• EMDBエントリー: 32743
• 分子名称: Spike glycoprotein, 510A5 light chain, 510A5 heavy chain, ... (5 entities in total)
• 機能のキーワード: covid-19, spike glycoprotein, virus, viral protein, antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 435240.75

構造登録者

Guo, H.,Gao, Y.,Ji, X.,Yang, H. (登録日: 2022-01-28, 公開日: 2022-06-01, 最終更新日: 2025-06-25)

主引用文献

Guo, H.,Gao, Y.,Li, T.,Li, T.,Lu, Y.,Zheng, L.,Liu, Y.,Yang, T.,Luo, F.,Song, S.,Wang, W.,Yang, X.,Nguyen, H.C.,Zhang, H.,Huang, A.,Jin, A.,Yang, H.,Rao, Z.,Ji, X.
Structures of Omicron spike complexes and implications for neutralizing antibody development.
Cell Rep, 39:110770-110770, 2022

PubMed Abstract: The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.

PubMed: 35477022
DOI: 10.1016/j.celrep.2022.110770

実験手法

ELECTRON MICROSCOPY (3.7 Å)