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 Asn 501 →Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change-for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
【초록키워드】 severe acute respiratory syndrome coronavirus 2, Evolution, antibodies, SARS-CoV-2, ACE2, coronavirus, Mutation, antibody, variant, Delta, severe acute respiratory syndrome Coronavirus, omicron, angiotensin-converting enzyme 2, variants, RBD, N501Y, Interpretation, substitutions, Alpha, SARS-CoV-2 evolution, Beta, spike receptor-binding domain, epistasis, receptor, respiratory, Angiotensin-converting enzyme, Amino acid, angiotensin, Eta, RBDs, ACE2 binding, acute respiratory syndrome, Recognition, acute respiratory syndrome coronavirus, phenomenon, Substitution, Wuhan-Hu-1, Effect, Affect, performed, example, subsequent, facilitate, occur, modulating, 【제목키워드】 viral evolution, domain, the SARS-CoV-2,