Fig. 5: Binding affinities and interactions of human ACE2 with different RBDs.

a Binding curves of immobilized human ACE2 with the SARS-CoV-2 (left panel), PCoV_GX (middle panel), or RaTG13 (right panel) RBD. Data are shown as different colored lines and the best fit of the data to a 1:1 binding model is shown in black. b Sequence alignment of the RBMs from the SARS-CoV-2, PCoV_GX, and RaTG13 spikes (left panel). Residues in the SARS-CoV-2 RBM that contact with hACE2 are indicated by red dots. The SARS-CoV-2 RBD (colored in cyan) and hACE2 (colored in wheat) are shown as cartoon (right panel, PDB ID: 6M0J). Six residues Y449, F486, Q493, Q498, N501, and Y505 in the RBM of SARS-CoV-2 that are not conserved in the RaTG13 are shown as dots. c Important sites accounting for different binding strength of hACE2 with the RaTG13 and SARS-CoV-2 RBDs (SARS-CoV-2 RBD-hACE2 interface: PDB ID 6M0J). The RBDs are showed as cyan cartoon and the hACE2 is showed in wheat cartoon or surface with electrostatic potential. Hydrogen bonds between SARS-CoV-2 Y449 and hACE2 D38 and Q42 would be abolished after Y to F mutation in the RaTG13 RBM (two leftmost panels). SARS-CoV-2 N501 mutation to D501 in RaTG13, contacting the hACE2 local negatively charged surface would disfavor the binding of hACE2 with the RaTG13 RBD (two middle panels). Hydrogen bonds between SARS-CoV-2 Y505 and hACE2 E37 and R393 would be abolished after Y to H mutation in the RaTG13 RBM (two rightmost panels).