Biophysical characterization of the SARS-CoV2 spike protein binding with the ACE2 receptor explains increased COVID-19 pathogenesis

Ratul Chowdhury; Costas D Maranas

We believe that the computational results presented herein are responsive to the recent call to contrast the two SARS-CoV and OC43 strains heralded in the recent press release (March 20, 2020) by the Scripps Research Institute 9 . We also provide key biophysical insights to explain the difference in pathogenicity of SARS-CoV-2 in comparison to OC43 and SARS-CoV-1. Multiple lines of computational evidence indicate that the spike RBDs gain entry into the human cell through electrostatic attachment with every fourth residue on the N-terminal alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. Results from computational models of canine, feline, bovine, equine, and chicken ACE2 in complex with SARS-CoV-2 spike RBD reveal residue-level underpinnings that explain why felines show highest, canines much lower, and chicken almost no susceptibility to COVID-