Fig. 3

The mutations that impair the global folding of RBD are evolutionally conserved. a The residues of which alanine substitution impaired RBD antigenic conformation and ACE2 binding ability are shown in a surface representation (PDB ID: 6M0J). Mutants located in the core region are highlighted in green and RBM are in cyan. Yellow sticks indicate disulfide bridges. b Conservation of residues that are essential for RBD folding across clades of sarbecoviruses. Human and animal SARS-related coronaviruses were classified by clades. SARS-CoV-2 genome sequences (n = 364,409) retrieved from GISAID and Genbank on January 19, 2021 (n = 11,839) and human SARS-CoV genome sequences (n = 200) from Genbank were used to annotate variants of the spike glycoprotein. Dashes indicate identity to SARS-CoV-2 consensus residues. Variants found in at least two sequences are parenthesized. c Top predicated destabilizing mutants by structural analysis. The score of MAESTRO and DUET is for predicted impact on stability from the RBD structure (PDB ID: 7C01). Average percent binding versus wildtype RBD for conformation-dependent RBD antibodies are shown