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

preprint
submitted on 08.10.2020 and posted on 08.10.2020 by CH Suresh
SARS-CoV-2 S-protein:human ACE2 complex models.
QM-MM optimized active site model of SARS-CoV-2 S-protein:human ACE2 interface.
ONIOM(B3LYP/6-31G*:PM7) method is the chosen QM-MM method.
DFT B3LYP/6-31G* level data on energetics is reported for drug-receptor interaction.
Several FDA approved drugs and traditional herbal isolates are modelled.
Used Gaussian16 to model the systems.


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 (Eb) of ML complexes increased with increase in dipole moment of Ls. Eb 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 Eb 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 Eb -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.

Funding

CSIR-NIIST funding for Covid-19 modelling

History

Email Address of Submitting Author

sureshch@gmail.com

Institution

CSIR–National Institute for Interdisciplinary Science and Technology (CSIR–NIIST)

Country

India.

ORCID For Submitting Author

0000-0001-7237-6638

Declaration of Conflict of Interest

No conflict of interest

Version Notes

First version

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