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