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

Ratul Chowdhury; Costas D Maranas

The alanine scan of the spike protein RBD of SARS-CoV-1, on the other hand, shows less significant penalty to the binding score upon mutation to alanine. Only six residues (Tyr436, Tyr440, Asn473, Tyr484, Thr486, and Thr487) are involved in strong electrostatic coupling with ACE2 residues (indicated in Table 1 ). In summary, alanine scans indicate that SARS-CoV-2 has the highest number of "effectively" interacting residues at the ACE2 binding interface whereas the SARS-CoV-1 spike forms only a few strong ACE2 connectors with a large number of "idle" interface residues (43% -7 out of 16) which do not affect ACE2 binding upon mutation to alanine. OC83 seems to be between the two with a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.015891 doi: bioRxiv preprint maximum number of weak electrostatic interactors (43% -7 out of 16) and only two idle residues at the interface (i.e., residues Asn239 and Tyr241). Table 1 . List of strong contacts between the spike RBDs from (SARS-CoV-2, SARS-CoV-1, and OC43) and human. ACE2