7E3C

SARS-CoV-2 spike in complex with the Ab1 neutralizing antibody (focused refinement on Fab-RBD)

Summary for 7E3C

• Entry DOI: 10.2210/pdb7e3c/pdb
• EMDB information: 30979
• Descriptor: Spike protein S1, Light chain of Ab1, Heavy chain of Ab1, ... (4 entities in total)
• Functional Keywords: spike, sars-cov-2, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 3
• Total formula weight: 94122.40

Authors

Liu, C. (deposition date: 2021-02-08, release date: 2021-09-01, Last modification date: 2024-10-30)

Primary citation

Nie, J.,Xie, J.,Liu, S.,Wu, J.,Liu, C.,Li, J.,Liu, Y.,Wang, M.,Zhao, H.,Zhang, Y.,Yao, J.,Chen, L.,Shen, Y.,Yang, Y.,Wang, H.W.,Wang, Y.,Huang, W.
Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants.
Cell Discov, 7:53-53, 2021

PubMed Abstract: Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.

PubMed: 34285195
DOI: 10.1038/s41421-021-00292-z

Experimental method

ELECTRON MICROSCOPY (4.2 Å)