Epistasis and background dependence in the evolution of Omicron variants of the SARS-CoV-2 Spike protein.

ABSTRACT: The rapid and repeated emergence of SARS-CoV-2 variants, particularly within the Omicron lineage, highlights the virus's remarkable ability to adapt under shifting immune pressures. A central molecular battleground in this evolutionary arms race is the spike receptor-binding domain (RBD), which must simultaneously maintain high affinity for the human ACE2 receptor while evading recognition by neutralizing antibodies. In this study, we construct and analyze multiple combinatorial libraries of SARS-CoV-2 RBD variants spanning major branches of Omicron evolution, including BA.1, BA.2, BA.5, XBB, and JN.1. Using high-throughput yeast display and binding assays, we map the effects of thousands of mutations and their combinations on ACE2 binding and antibody evasion. Our results reveal that whil

SUBMITTER: Moulana A 

PROVIDER: S-EPMC12667959 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature