Figure 2.

The spike protein of Omicron variant carries mutations that confer utility of mouse ACE2 for entry

(A) Illustration of all changes found in the Omicron isolate used in this study (hCoV-19/USA/MD-HP20874/2021) compared with USA-WA1/2020. Coincidentally, the Omicron spike protein in pseudoviruses carries an identical number of changes.

(B–E) Various coordinations of charged residues at the ACE2-RBD interface: (B) hACE2-wtRBD (buried charge: 0), (C) mACE2-wtRBD (buried charge: −2 e), (D) hACE2-oRBD (buried charge: +2 e), and (E) mACE2-oRBD (buried charge: 0).

(F and G) Detailed interfacial coordinations between mACE2 and oRBD.

(F) The interfacial binding near the salt bridge R498-D38.

(G) The interfacial binding near the salt bridge R493-E35.

(H and I) Pseudoviruses carrying WA1 spike with indicated combinations of mutations infected 293T-hACE2 or 293-mACE2 cell lines.

(J) Cell-cell fusion is mediated by WA1 spike or Omicron spike or the WA1-Q493R/N501Y spike protein.

Results in each bar graph contain at least three technical replicates. Data shown here are representatives of two independent experiments.