7Y0C

Crystal structure of BD55-1403 and SARS-CoV-2 Omicron RBD

Summary for 7Y0C

• Entry DOI: 10.2210/pdb7y0c/pdb
• Descriptor: BD55-1403 Fab light chain, BD55-1403 Fab heavy chain, Spike protein S1, ... (5 entities in total)
• Functional Keywords: sars-cov-2, omicron variants, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 139552.38

Authors

Zhang, Z.,Xiao, J. (deposition date: 2022-06-04, release date: 2022-09-28, Last modification date: 2024-11-20)

Primary citation

Cao, Y.,Jian, F.,Zhang, Z.,Yisimayi, A.,Hao, X.,Bao, L.,Yuan, F.,Yu, Y.,Du, S.,Wang, J.,Xiao, T.,Song, W.,Zhang, Y.,Liu, P.,An, R.,Wang, P.,Wang, Y.,Yang, S.,Niu, X.,Zhang, Y.,Gu, Q.,Shao, F.,Hu, Y.,Yin, W.,Zheng, A.,Wang, Y.,Qin, C.,Jin, R.,Xiao, J.,Xie, X.S.
Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents.
Cell Rep, 41:111845-111845, 2022

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities.

PubMed: 36493787
DOI: 10.1016/j.celrep.2022.111845

Experimental method

X-RAY DIFFRACTION (2.94 Å)