bind_escape_code_and_data

Despite numerous studies investigating SARS-CoV-2 ACE2 binding affinity and its transmissibility, their relationship concerning varying immunity remains unclear. ACE2 binding affinity and immune escape were calculated for each viral sequence by summing the effects of all amino acid mutations in the receptor-binding domain, using deep mutational scanning data. The daily averages of these two traits were then computed across all sequences isolated each day to track their evolution over time. We developed an infectious disease transmission model that decomposed the effective reproduction number into three time-varying components: viral infectiousness, host susceptibility (determined by immune protection), and contact rate. Viral infectiousness represented a fitness component determined by both ACE2 binding and the immunity level of infected hosts. By fitting the model to daily number of reported cases, immune escape, vaccine rollout and population mobility, both viral infectiousness and the immune protection against the circulating variants (referred to as effective immunity) among infected individuals were quantified. A rugged fitness landscape, spanned by ACE2 binding and hosts' effective immunity, was observed with peaks corresponding to individual VOCs (alpha, delta, and omicron (BA.1* and BA.2*)). We found that increasing effective immunity was associated with decreasing virus fitness peaks before Omicron, whereas decreasing effective immunity and weaker receptor binding were associated with an optimal virus fitness later on. The finding helps understand SARS-CoV-2 evolution and predict future dominant variants.