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Article: 35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope

Title35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope
Authors
Keywords35B5
antigenic shift
dissociation
glycan
monoclonal antibody
neutralization
Omicron
RBD
SARS-CoV-2
spike protein
Issue Date2022
Citation
Cell Host & Microbe, 2022, v. 30 n. 6, p. 887-895.e4 How to Cite?
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 (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.
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.
Persistent Identifierhttp://hdl.handle.net/10722/314520
ISSN
2023 Impact Factor: 20.6
2023 SCImago Journal Rankings: 7.760
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, X-
dc.contributor.authorChen, X-
dc.contributor.authorTan, J-
dc.contributor.authorYue, S-
dc.contributor.authorZhou, R-
dc.contributor.authorXu, Y-
dc.contributor.authorLin, Y-
dc.contributor.authorYang, Y-
dc.contributor.authorZhou, Y-
dc.contributor.authorDeng, K-
dc.contributor.authorChen, Z-
dc.contributor.authorYe, L-
dc.contributor.authorZhu, Y-
dc.date.accessioned2022-07-22T05:26:06Z-
dc.date.available2022-07-22T05:26:06Z-
dc.date.issued2022-
dc.identifier.citationCell Host & Microbe, 2022, v. 30 n. 6, p. 887-895.e4-
dc.identifier.issn1931-3128-
dc.identifier.urihttp://hdl.handle.net/10722/314520-
dc.description.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 (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.-
dc.description.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 (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.-
dc.languageeng-
dc.relation.ispartofCell Host & Microbe-
dc.subject35B5-
dc.subjectantigenic shift-
dc.subjectdissociation-
dc.subjectglycan-
dc.subjectmonoclonal antibody-
dc.subjectneutralization-
dc.subjectOmicron-
dc.subjectRBD-
dc.subjectSARS-CoV-2-
dc.subjectspike protein-
dc.title35B5 antibody potently neutralizes SARS-CoV-2 Omicron by disrupting the N-glycan switch via a conserved spike epitope-
dc.typeArticle-
dc.identifier.emailZhou, R: zhourh@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.doi10.1016/j.chom.2022.03.035-
dc.identifier.pmid35436443-
dc.identifier.pmcidPMC8960183-
dc.identifier.scopuseid_2-s2.0-85128280115-
dc.identifier.hkuros334610-
dc.identifier.volume30-
dc.identifier.issue6-
dc.identifier.spage887-
dc.identifier.epage895.e4-
dc.identifier.isiWOS:000882918200016-

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