7XMZ

Cryo-EM structure of SARS-CoV-2 spike glycoprotein in complex with three D2 Fab

7XMZ の概要

• エントリーDOI: 10.2210/pdb7xmz/pdb
• EMDBエントリー: 33308
• 分子名称: Spike glycoprotein, D2 heavy chain, D2 light chain, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, spike, antibody, viral protein
• 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: 9
• 化学式量合計: 512410.81

構造登録者

Wang, X.,Li, X. (登録日: 2022-04-27, 公開日: 2022-11-23)

主引用文献

Li, X.,Pan, Y.,Yin, Q.,Wang, Z.,Shan, S.,Zhang, L.,Yu, J.,Qu, Y.,Sun, L.,Gui, F.,Lu, J.,Jing, Z.,Wu, W.,Huang, T.,Shi, X.,Li, J.,Li, X.,Li, D.,Wang, S.,Yang, M.,Zhang, L.,Duan, K.,Liang, M.,Yang, X.,Wang, X.
Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages.
Cell Discov, 8:87-87, 2022

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

PubMed: 36075908
DOI: 10.1038/s41421-022-00449-4

実験手法

ELECTRON MICROSCOPY (3.25 Å)