Fig. 1. Omicron sublineage RBDs bind ACE2 with enhanced affinity but exhibit impaired S-mediated fusogenicity relative to the ancestral virus.
(A to C) Prevalence of the different variants of concern measured globally (A), in the United States (B), or in South Africa (C). Alpha comprises B.1.1.7 and all Q sublineages; Delta comprises B.1.617.2 and all AY sublineages; and BA.1, BA.2, BA.4, and BA.5 comprise their respective sublineages (including BA.2.12.1 for BA.2). Prevalence calculations rely on shared GISAID (Global Initiative on Sharing Avian Influenza Data) sequences and may be biased by sampling. (D and E) Equilibrium dissociation constants (KD) of binding of the monomeric ACE2 ectodomain to immobilized biotinylated Wuhan-Hu-1, Delta, BA.1, BA.2, BA2.12.1, and BA.4/5 RBDs assessed by BLI (D) or SPR (E). Data presented are the results of at least two independent biological replicates for BLI and for SPR (except for the BA.1 RBD SPR data, which come from four technical replicates). (F) Quantification of cell-cell fusion after 24 hours mediated by Wuhan-Hu-1/G614, Delta, BA.1, BA.2, BA.2.12.1, and BA.4/5 S glycoproteins expressed as the fraction of the total area with GFP fluorescence assessed using a split GFP system. Data are from 16 fields of view from a single experiment and are representative of results obtained from two independent biological replicates. Comparisons between fusion mediated by the Wuhan-Hu-1/G614 S and other S variants were completed using the Wilcoxon rank sum test. **P < 0.01; ***P < 0.001; ****P < 0.0001. (G) Kinetics of cell-cell fusion mediated by Wuhan-Hu-1/G614, Delta, BA.1, BA.2, BA.2.12.1, and BA.4/5 S glycoproteins expressed as the fraction of the total area with GFP fluorescence assessed using a split GFP system.