Drug and Drug-like Molecule Binding to Interface of SARS-CoV-2 Sprotein:human ACE2 Complex: A Density Functional Theory Study

The interface cavity of SARS-CoV-2 S-protein:human ACE2 complex (M) for ligand (L) binding is modelled using a two layer ONIOM(B3LYP/6-31G*:PM7) method for sixteen traditional herbal isolates (THI) and nineteen drugs. The binding energy (E_b) of ML complexes increased with increase in dipole moment of Ls. E_b better than -80.0 kcal/mol is observed for digallic acid and adenosine 3',5'-bisphosphate whereas myricetin, glucogallin, sapropterin, tetrahydrobiopterin, protirelin and fidarestat showed E_b better than -60.0 kcal/mol. Multiple noncovalent interactions emanating from arginine, histidine, tyrosine, lysine, carboxylate and amide units (total around 6 - 8) of L, S-protein and ACE2 receptors provide the high binding energy. The sugar substitute aspartame modified with myricetin unit showed the best E_b -91.7 kcal/mol. ONIOM-linked DFT study is effective, affordable and reliable for a quantum chemical rational design approach to model drug-receptor binding process for COVID-19 drug development which sheds light upon the noncovalent binding features of receptor cavity.