Extended Data Fig. 4: EVEscape enrichment in regions of SARS-CoV-2 Spike.
From: Learning from prepandemic data to forecast viral escape
a) RBD (particularly receptor binding motif (RBM)) and N-terminal domain (NTD) have significantly enriched average EVEscape scores, relative to a distribution of 500 random contiguous regions of the same length from full Spike. Fusion peptide (not known for escape mutations) does not have enriched average EVEscape scores. b) EVEscape predictions cover diverse epitope regions across Spike and diverse RBD antibody classes (Supplementary Methods) (3D structure of RBD on the right), including known immunodominant sites (E484, K417, L452) (PDB ID: 7BNN). The regions considered are NTD (sequence positions 14 − 306), RBD (319 − 542), S1* (543 − 685), and S2 (686 − 1273), where S1* refers to the region in S1 between RBD and S2. c) Average region EVEscape predictions are highest in RBD and NTD, although NTD is more mutationally tolerant based on average fitness (EVE) score. d) EVEscape scores experimental escape mutants from narrow antibodies and broad neutralizing antibodies higher than those from broad, non-neutralizing antibodies. Sarbecovirus binding breath and neutralization from Starr et al. 8 Bounds of boxplot are quartiles with the median as the measure of center.
