A unified topology-based classification of SARS-CoV-2 RBD neutralizing antibodies systematizes affinity trends across variants.

ABSTRACT: The receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, responsible for engaging the hACE2 receptor, is the principal target of neutralizing antibodies (NAb). To better understand how viral evolution undermines NAb protection, we present a comprehensive, topology-based classification derived from 544 NAbs and 60 nanobody-RBD complex structures. Five major NAb classes, each subdivided into two subclasses, were defined by binding zone, angle of approach, hACE2 competition, and hotspot usage. A systematic mapping of NAb-antigen contacts revealed 91 recurrent hotspot residues, some of which remain fully conserved across all Omicron variants. Leveraging > 2,300 experimentally dissociation constants spanning the Wuhan strain and Omicron lineages, we conducted a comparative affinity an

SUBMITTER: Cofas-Vargas LF 

PROVIDER: S-EPMC12542604 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature