Computational Mutagenesis at the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Binding Interface: Comparison with Experimental Evidence

The coronavirus disease-2019 (COVID-19) pandemic, caused by the pathogen severe acute respiratory syndrome 2 (SARS-CoV-2), started in China during late 2019 and swiftly spread worldwide. Since COVID-19 emergence, many therapeutic regimens have been relentlessly explored, although two vaccines just received emergency use authorization different governmental agencies, antiviral therapeutics based neutralizing antibodies small-drug inhibitors can still be vital viable options to prevent treat SARS-CoV-2 infections. viral spike glycoprotein (S-protein) is key molecular player that promotes human host cellular invasion via recognition of binding angiotensin-converting enzyme gene (ACE2). In this work, we report results obtained mutating silico 18 ACE2 residues 14 S-protein receptor domain (S-RBDCoV-2) contribute receptor/viral protein interface. Specifically, each wild-type protein–protein interface residue was replaced a hydrophobic (isoleucine), polar (serine threonine), charged (aspartic acid/glutamic acid lysine/arginine), bulky (tryptophan) residue, respectively, order study effects exerted nature, shape, dimensions mutant amino acids on structure strength resulting computational were next validated posteriori against corresponding experimental data, yielding an overall agreement 92%. Interestingly, non-negligible number mis-sense variations predicted enhance ACE2/S-RBDCoV-2 binding, including variants Q24T, T27D/K/W, D30E, H34S7T/K, E35D, Q42K, L79I/W, R357K, R393K L455D/W, F456K/W, Q493K, N501T, Y505W S-RBDCoV-2, respectively.