Fig. 3: Impact of selective forces on SARS-CoV-2 infectivity and antibody neutralization.

A For each possible amino acid substitution within the RBD, the effect of the mutation on RBD expression (x-axis) and ACE2 binding (y-axis). Each substitution is colored according to whether its associated site is under diversifying (red), purifying (blue), or neutral (gray) selection. B Levels of diversifying and purifying selection of each antibody epitope class site during the pre-vaccine and current post-Omicron eras. C Sites detected to be under purifying selection (blue) or diversifying selection (red) within the RBD of the S protein. Overlayed are the sites associated with class 1 (green), 2 (orange), 3 (navy blue), and 4 (yellow) antibody epitopes. D Deep mutational scan site total escape from convalescent plasma values for sites under diversifying (red), purifying (blue), or neutral (gray) selection. E Boxplot of the incident rates (cases per 100,000) for each sample in the pre-vaccination era (collected in 2020), grouped by whether that sample contained a mutation that reduced neutralization (G446V or mutations at sites L452, E484, or K417), increased ACE2 binding without any impact on neutralization (T478K or mutations at sites N501 or S477), or had no effect on neutralization and binding (A520S or mutations at site A522).