7CWN

P17-H014 Fab cocktail in complex with SARS-CoV-2 spike protein

7CWN の概要

• エントリーDOI: 10.2210/pdb7cwn/pdb
• EMDBエントリー: 30484
• 分子名称: Spike glycoprotein, heavy chain of P17 Fab, light chain of P17 Fab, ... (7 entities in total)
• 機能のキーワード: cocktail, complex, sars-cov-2 spike protein, fab, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 708048.56

構造登録者

Wang, N.,Wang, X. (登録日: 2020-08-29, 公開日: 2020-12-16, 最終更新日: 2024-11-06)

主引用文献

Yao, H.,Sun, Y.,Deng, Y.Q.,Wang, N.,Tan, Y.,Zhang, N.N.,Li, X.F.,Kong, C.,Xu, Y.P.,Chen, Q.,Cao, T.S.,Zhao, H.,Yan, X.,Cao, L.,Lv, Z.,Zhu, D.,Feng, R.,Wu, N.,Zhang, W.,Hu, Y.,Chen, K.,Zhang, R.R.,Lv, Q.,Sun, S.,Zhou, Y.,Yan, R.,Yang, G.,Sun, X.,Liu, C.,Lu, X.,Cheng, L.,Qiu, H.,Huang, X.Y.,Weng, T.,Shi, D.,Jiang, W.,Shao, J.,Wang, L.,Zhang, J.,Jiang, T.,Lang, G.,Qin, C.F.,Li, L.,Wang, X.
Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.
Cell Res., 31:25-36, 2021

PubMed Abstract: Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

PubMed: 33262452
DOI: 10.1038/s41422-020-00444-y

実験手法

ELECTRON MICROSCOPY (3.2 Å)