Fig. 4: Interaction between BQ.1.1 S and ACE2.
From: Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant
a Binding affinity of the receptor binding ___domain (RBD) of the SARS-CoV-2 S protein to ACE2 by yeast surface display. The dissociation constant (KD) value indicating the binding affinity of the RBD of the SARS-CoV-2 S protein to soluble ACE2 when expressed on yeast is shown. b Pseudovirus assay. HOS-ACE2/TMPRSS2 cells were infected with pseudoviruses bearing each S protein. The amount of input virus was normalized based on the amount of HIV-1 p24 capsid protein. The percent infectivity compared to that of the virus pseudotyped with the BA.2 S protein are shown. c, Fold increase in pseudovirus infectivity based on TMPRSS2 expression. d–f The BQ.1.1 RBD bound to ACE2 trapped in the closed conformation. d Crystal structure of the BQ.1.1 RBD-human ACE2 complex. Characteristic substitutions in the BQ.1.1 RBD and an N-linked glycan on N90 of human ACE2 are shown in purple and gray sticks. In the close-up view, corresponding residues in the BA.4/5 RBD-human ACE2 complex structure (PDB: 7XWA)17 are also shown in brown sticks. The BQ.1.1 RBD and ACE2 residues recognizing the glycan are shown in stick representation. Dashed lines represent hydrogen bonds. e Superimposition of the BQ.1.1 RBD-human ACE2 complex structure (purple) onto previously reported structures of SARS-CoV-2 RBD bound to human ACE2. BQ.1.1, purple; BA.227, pale green, PDB: 7ZF7; BA.2.7530, khaki, PDB: 8ASY; BA.517, brown, PDB: 7XWA. BA.2, BA.2.75. BA.5 are shown as transparent. f Superimposition of the BQ.1.1 RBD-human ACE2 complex structure (purple) onto a previously reported structure of an inhibitor bound human ACE2 (pale yellow, PDB: 1R4L)28. Assays were performed in triplicate (a) or quadruplicate (b). The presented data are expressed as the average ± standard deviation (SD) (a–c). Each dot indicates the result of an individual replicate. The dashed horizontal lines indicate the value of BA.5. Statistically significant differences versus each parental S protein and those between BA.5 and BQ.1.1 were determined by two-sided Student’s t tests.
