7WRJ
Local CryoEM structure of the SARS-CoV-2 S6P(B.1.1.529) in complex with BD55-4637 Fab
Summary for 7WRJ
| Entry DOI | 10.2210/pdb7wrj/pdb |
| EMDB information | 32728 |
| Descriptor | Spike protein S1, BD55-4637H, BD55-4637L, ... (4 entities in total) |
| Functional Keywords | antibody, complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 3 |
| Total formula weight | 74999.52 |
| Authors | Du, S.,Xiao, J.Y. (deposition date: 2022-01-26, release date: 2022-09-28, Last modification date: 2024-10-16) |
| 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 Cited by 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: 36493787DOI: 10.1016/j.celrep.2022.111845 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.08 Å) |
Structure validation
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