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

Autor:	Duyvesteyn HME; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Centre for Human Genetics, Oxford, UK., 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., 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., 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., 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., Jeffery K; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Stafford L; Oxford University Hospitals NHS Foundation Trust, Oxford, UK., 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., 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., 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., 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., 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., 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., 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.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2024 Oct 03; Vol. 32 (10), pp. 1594-1602.e6. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1016/j.str.2024.07.020
Abstrakt:	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. Competing Interests: 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. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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