Concerted deletions eliminate a neutralizing supersite in SARS-CoV-2 BA.2.87.1 spike.

BA.2.87.1 N-terminal domain SARS-CoV-2 SARS-CoV-2 variants cryo-EM neutralization protein structure spike protein structural virology virus glycoprotein

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
16 Aug 2024
Historique:
received: 16 05 2024
revised: 01 07 2024
accepted: 29 07 2024
medline: 23 8 2024
pubmed: 23 8 2024
entrez: 22 8 2024
Statut: aheadofprint

Résumé

BA.2.87.1 represents a major shift in the BA.2 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is unusual in having two lengthy deletions of polypeptide in the spike (S) protein, one of which removes a beta-strand. Here we investigate its neutralization by a variety of sera from infected and vaccinated individuals and determine its spike (S) ectodomain structure. The BA.2.87.1 receptor binding domain (RBD) is structurally conserved and the RBDs are tightly packed in an "all-down" conformation with a small rotation relative to the trimer axis as compared to the closest previously observed conformation. The N-terminal domain (NTD) maintains a remarkably similar structure overall; however, the rearrangements resulting from the deletions essentially destroy the so-called supersite epitope and eliminate one glycan site, while a mutation creates an additional glycan site, effectively shielding another NTD epitope. BA.2.87.1 is relatively easily neutralized but acquisition of additional mutations in the RBD could increase antibody escape allowing it to become a dominant sub-lineage.

Identifiants

DOI: 10.1016/j.str.2024.07.020 PMID: 39173622
pubmed: 39173622
pii: S0969-2126(24)00283-1
doi: 10.1016/j.str.2024.07.020
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. D.I.S. consults for AstraZeneca. Oxford University holds intellectual property related to SARS-CoV-2 mAbs discovered in G.R.S.’s laboratory. S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19.

Auteurs

Helen M E Duyvesteyn (HME)

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Centre for Human Genetics, Oxford, UK.

Aiste Dijokaite-Guraliuc (A)

Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Chang Liu (C)

Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Piyada Supasa (P)

Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Barbara Kronsteiner (B)

NDM Centre For Global Health Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.

Katie Jeffery (K)

Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Lizzie Stafford (L)

Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Paul Klenerman (P)

Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Susanna J Dunachie (SJ)

Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Juthathip Mongkolsapaya (J)

Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand. Electronic address: juthathip.mongkolsapaya@well.ox.ac.uk.

Elizabeth E Fry (EE)

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Centre for Human Genetics, Oxford, UK. Electronic address: liz@strubi.ox.ac.uk.

Jingshan Ren (J)

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Centre for Human Genetics, Oxford, UK. Electronic address: ren@strubi.ox.ac.uk.

David I Stuart (DI)

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot, UK. Electronic address: dave@strubi.ox.ac.uk.

Gavin R Screaton (GR)

Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: gavin.screaton@medsci.ox.ac.uk.

Classifications MeSH