Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single-amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn⁵⁰¹→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change-for example

SUBMITTER: Starr TN 

PROVIDER: S-EPMC9273037 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature