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7XH8

The structure of ZCB11 Fab against SARS-CoV-2 Omicron Spike

Summary for 7XH8
Entry DOI10.2210/pdb7xh8/pdb
EMDB information33191
DescriptorSpike glycoprotein, The heavy chain of ZCB11 antibody, The light chain of ZCB11 antibody (3 entities in total)
Functional Keywordssarc-cov-2 omicron spike, fab, antibody, viral protein, immune system, viral protein-immune system complex, viral protein/immune system
Biological sourceSevere acute respiratory syndrome coronavirus 2
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Total number of polymer chains3
Total formula weight181129.98
Authors
Hang, L.,Dang, S. (deposition date: 2022-04-07, release date: 2022-06-29, Last modification date: 2024-07-03)
Primary citationZhou, B.,Zhou, R.,Tang, B.,Chan, J.F.,Luo, M.,Peng, Q.,Yuan, S.,Liu, H.,Mok, B.W.,Chen, B.,Wang, P.,Poon, V.K.,Chu, H.,Chan, C.C.,Tsang, J.O.,Chan, C.C.,Au, K.K.,Man, H.O.,Lu, L.,To, K.K.,Chen, H.,Yuen, K.Y.,Dang, S.,Chen, Z.
A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.
Nat Commun, 13:3589-3589, 2022
Cited by
PubMed Abstract: The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.
PubMed: 35739114
DOI: 10.1038/s41467-022-31259-7
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.99 Å)
Structure validation

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