Comprehensive analysis of SARS-CoV-2 Spike evolution: epitope classification and immune escape prediction.

ABSTRACT: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, has produced unprecedented numbers of structures of the Spike protein. In this study, we present a comprehensive analysis of 1560 published structures, covering most major variants that emerged throughout the pandemic, diverse heteromerization, and interacting complexes. Using interaction-energy-informed geometric clustering, we identify 14 structurally distinct epitopes based on their conformational specificity, shared interface with angiotensin-converting enzyme 2 (ACE2), and glycosylation patterns. Our per-residue interaction evaluations accurately predict antibody recognition sites and correlate strongly with deep mutational scanning data, enabling immune esca

SUBMITTER: Teruel NFB 

PROVIDER: S-EPMC12159738 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature