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TitleA broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 3589, Year 2022
Publish dateJun 23, 2022
AuthorsBiao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / Hin Chu / Chris Chung-Sing Chan / Jessica Oi-Ling Tsang / Chris Chun-Yiu Chan / Ka-Kit Au / Hiu-On Man / Lu Lu / Kelvin Kai-Wang To / Honglin Chen / Kwok-Yung Yuen / Shangyu Dang / Zhiwei Chen /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:35739114 / PubMed Central
MethodsEM (single particle)
Resolution2.99 - 3.56 Å
Structure data

33191

7xh8

EMDB-33191, PDB-7xh8:
The structure of ZCB11 Fab against SARS-CoV-2 Omicron Spike
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-33194: The Cryo-EM structure of SARS-CoV-2 Omicron 2-RBD up spike protein complexed with ZCB11 fab
Method: EM (single particle) / Resolution: 3.47 Å

EMDB-33195: The Cryo-EM structure of SARS-CoV-2 Omicron 3-RBD up spike protein complexed with ZCB11 fab
Method: EM (single particle) / Resolution: 3.56 Å

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARC-CoV-2 Omicron Spike / Fab / Antibody / viral protein / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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