<p>Species tropism of bat and mammalian ACE with SARS-CoV-2 variants.</p>

<p><b>(A)</b> Schematic of the emergence of SARS-CoV-2 variants depicting the divergence of the B lineage variants, including those variants of concern that grew to global dominance (B.1, Alpha, Beta, Delta, Omicron [black lines]), and the Omicron subvariants [red lines], some of which emerged via recombination events (dotted lines). Heatmap showing the bat and mammalian ACE2 usage of SARS-CoV-2 variants with <b>(B)</b> the B.1, Alpha, Beta, Delta and BA.1 variants, or <b>(E)</b> BA.2 and its subvariants BA.4/5, XBB, XBB1.5, BA.2.86.

Data are shown as the mean fold change in pseudotype entry (RLU) of 3 separate experiments, relative to human ACE2. <b>(C)</b> Structure of SARS-CoV-2 BA.1 (PDB 7XO7) with mutations listed compared to B.1. Zoomed images of the Spike protein for B.1 (PDB 6M0J) and BA.1 (PDB 7WBP), highlighting key residues at positions 417, 484, 493 and 501 and the resultant interactions with human ACE2. <b>(D)</b> Specific amino acids within the B.1 RBD were mutagenised to make the RBD more BA.1-like (K417N, E484A, Q493R or N501Y) (top panel), or within BA.1 RBD to make the RBD more B.1-like (N417K, A484E, R493Q or Y501N) (bottom panel), either by themselves or in combination.