7BYR

BD23-Fab in complex with the S ectodomain trimer

Summary for 7BYR

• Entry DOI: 10.2210/pdb7byr/pdb
• EMDB information: 30247
• Descriptor: Spike glycoprotein, Ab23-Fab-Heavy Chain, Ab23-Fab-Light Chain, ... (6 entities in total)
• Functional Keywords: sars-cov-2, antigen, rbd, neutralizing antibody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 5
• Total formula weight: 450015.61

Authors

Zhu, Q.,Wang, G.,Xiao, J. (deposition date: 2020-04-24, release date: 2020-06-10, Last modification date: 2021-03-10)

Primary citation

Cao, Y.,Su, B.,Guo, X.,Sun, W.,Deng, Y.,Bao, L.,Zhu, Q.,Zhang, X.,Zheng, Y.,Geng, C.,Chai, X.,He, R.,Li, X.,Lv, Q.,Zhu, H.,Deng, W.,Xu, Y.,Wang, Y.,Qiao, L.,Tan, Y.,Song, L.,Wang, G.,Du, X.,Gao, N.,Liu, J.,Xiao, J.,Su, X.D.,Du, Z.,Feng, Y.,Qin, C.,Qin, C.,Jin, R.,Xie, X.S.
Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.
Cell, 182:73-84.e16, 2020

PubMed Abstract: The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1 clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 Å cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3 structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.

PubMed: 32425270
DOI: 10.1016/j.cell.2020.05.025

Experimental method

ELECTRON MICROSCOPY (3.84 Å)