7E23

SARS-CoV-2 spike in complex with the CA521 neutralizing antibody Fab (focused refinement on Fab-RBD)

7E23 の概要

• エントリーDOI: 10.2210/pdb7e23/pdb
• EMDBエントリー: 30950
• 分子名称: Spike protein S1, CA521 Heavy Chain, CA521 Light Chain, ... (4 entities in total)
• 機能のキーワード: spike, sars-cov-2, antibody, 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: 3
• 化学式量合計: 94468.60

構造登録者

Liu, C.,Song, D.,Dou, C. (登録日: 2021-02-04, 公開日: 2021-05-05, 最終更新日: 2025-07-02)

主引用文献

Song, D.,Wang, W.,Dong, C.,Ning, Z.,Liu, X.,Liu, C.,Du, G.,Sha, C.,Wang, K.,Lu, J.,Sun, B.,Zhao, Y.,Wang, Q.,Xu, H.,Li, Y.,Shen, Z.,Jiao, J.,Wang, R.,Tian, J.,Liu, W.,Wang, L.,Deng, Y.Q.,Dou, C.
Structure and function analysis of a potent human neutralizing antibody CA521 FALA against SARS-CoV-2.
Commun Biol, 4:500-500, 2021

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521 recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521 blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521 a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.

PubMed: 33893388
DOI: 10.1038/s42003-021-02029-w

実験手法

ELECTRON MICROSCOPY (3.3 Å)