7E23

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

Summary for 7E23

• Entry DOI: 10.2210/pdb7e23/pdb
• EMDB information: 30950
• Descriptor: Spike protein S1, CA521 Heavy Chain, CA521 Light Chain, ... (4 entities in total)
• Functional Keywords: spike, sars-cov-2, antibody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 3
• Total formula weight: 94468.60

Authors

Liu, C.,Song, D.,Dou, C. (deposition date: 2021-02-04, release date: 2021-05-05, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)