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Title35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope.
Journal, issue, pagesCell Host Microbe, Vol. 30, Issue 6, Page 887-895.e4, Year 2022
Publish dateJun 8, 2022
AuthorsXiaofei Wang / Xiangyu Chen / Jiaxing Tan / Shuai Yue / Runhong Zhou / Yan Xu / Yao Lin / Yang Yang / Yan Zhou / Kai Deng / Zhiwei Chen / Lilin Ye / Yongqun Zhu /
PubMed AbstractThe SARS-CoV-2 Omicron variant harbors more than 30 mutations in the spike protein, leading to immune evasion from many therapeutic neutralizing antibodies. We reveal that a receptor-binding domain ...The SARS-CoV-2 Omicron variant harbors more than 30 mutations in the spike protein, leading to immune evasion from many therapeutic neutralizing antibodies. We reveal that a receptor-binding domain (RBD)-targeting monoclonal antibody, 35B5, exhibits potent neutralizing efficacy to Omicron. Cryo-electron microscopy structures of the extracellular domain trimer of Omicron spike with 35B5 Fab reveal that Omicron spike exhibits tight trimeric packing and high thermostability, as well as significant antigenic shifts and structural changes, within the RBD, N-terminal domain (NTD), and subdomains 1 and 2. However, these changes do not affect targeting of the invariant 35B5 epitope. 35B5 potently neutralizes SARS-CoV-2 Omicron and other variants by causing significant conformational changes within a conserved N-glycan switch that controls the transition of RBD from the "down" state to the "up" state, which allows recognition of the host entry receptor ACE2. This mode of action and potent neutralizing capacity of 35B5 indicate its potential therapeutic application for SARS-CoV-2.
External linksCell Host Microbe / PubMed:35436443 / PubMed Central
MethodsEM (single particle)
Resolution2.98 - 3.4 Å
Structure data

32594

7wly

EMDB-32594, PDB-7wly:
Cryo-EM structure of the Omicron S in complex with 35B5 Fab(1 down- and 2 up RBDs)
Method: EM (single particle) / Resolution: 3.4 Å

32595

7wlz

EMDB-32595, PDB-7wlz:
Cryo-EM structure of the Omicron S in complex with 35B5 Fab(1 down-, 1 up- and 1 invisible RBDs)
Method: EM (single particle) / Resolution: 2.98 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / IMMUNE SYSTEM

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