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

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.

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Publication Details

Journal
Structure
Published
2024-08-22
DOI
https://doi.org/10.1016/j.str.2024.07.020
Citations
1
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.39

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article

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

Helen M. E. Duyvesteyn, Piyada Supasa, Katie Jeffery, Paul Klenerman et al.
1 citations
Structure
SARS-CoV-2 and COVID-19 Research
0.39
article

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

Helen M. E. Duyvesteyn, Piyada Supasa, Katie Jeffery, Paul Klenerman, Aiste Dijokaite-Guraliuc, Lizzie Stafford, David I. Stuart, Jingshan Ren, Juthathip Mongkolsapaya, Barbara Kronsteiner, Elizabeth E. Fry, Susanna Dunachie, Gavin Robert Screaton, Chang Liu
article en
1 citations

Abstract

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.

StructureVol. 32(10)
Centre for Human Genetics (GB), Angkor Hospital for Children (KH), University of Oxford (GB), Medawar Building for Pathogen Research (GB), Oxford BioMedica (United Kingdom) (GB), Science Oxford (GB), Oxford University Hospitals NHS Trust (GB)
Medical Research Council
Openalex Percentile: Top 38%
SARS-CoV-2 and COVID-19 Research
0.39
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