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

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually evolves, with new variants emerging.
• The BA.2 lineage has produced sub-lineages with significant genetic alterations.
• Understanding the structural and immunological impact of these changes is crucial for public health.

Purpose of the Study:

• To investigate the structural characteristics of the BA.2.87.1 SARS-CoV-2 variant.
• To assess the neutralization capabilities of sera against BA.2.87.1.
• To predict the potential for BA.2.87.1 to become a dominant sub-lineage.

Main Methods:

• Determination of the spike (S) ectodomain structure of BA.2.87.1.
• Analysis of receptor binding domain (RBD) and N-terminal domain (NTD) conformations.
• Evaluation of neutralization by sera from infected and vaccinated individuals.

Main Results:

• BA.2.87.1 exhibits two significant polypeptide deletions in its spike protein, including a beta-strand.
• The RBD remains structurally conserved in an 'all-down' conformation.
• Deletions disrupt the NTD supersite epitope and alter glycan site accessibility, potentially shielding other epitopes.

Conclusions:

• BA.2.87.1 is currently susceptible to neutralization.
• Structural changes in the NTD impact antibody binding sites.
• Acquisition of further mutations, particularly in the RBD, could confer increased antibody escape and lead to dominance.