Contact residue contributions to interaction energies between SARS-CoV-1 spike proteins and human ACE2 receptors

Abstract Several viruses of the corona family interact, via their spike (S) proteins, with human cellular receptors. Spike proteins SARS-CoV-1 and SARS-CoV-2 virions, being structurally related but not identical, mediate attachment to angiotensin-converting enzyme 2 (hACE2) receptor in similar non-identical ways. Molecular-level understanding interactions between hACE2 can aid strategies for blocking SARS-CoV-1, a potentially reemerging health threat, cells. We have identified dominant molecular-level interactions, some attractive repulsive, binding domain (S-RBD) hACE2. performed fragment-based quantum-biochemical calculations which directly relate biomolecular structure hACE2...S-RBD interaction energy. Consistent X-ray crystallography cryo-EM, energy S-RBD ( $$\approx -$$ ≈ - 26 kcal/mol) corresponds net intermolecular attraction is significantly enhanced by inclusion dispersion van der Waals forces. Protein fragments at interface, that dominate host-virus attraction, been together constituent amino acid residues. Two include residues (GLU37, ASP38, TYR41, GLN42) (GLU329, LYS353, GLY354), respectively, as well three (TYR436), (ARG426) (THR487, GLY488, TYR491), primary attractors interface.