Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic
is plaguing the entire world. Amidst the pandemic, research and development efforts are focused
on the challenges associated with the SARS-CoV-2 structure.
Materials and Methods: Efficient computational methodologies are applied to screen the available
FDA-approved drugs/datasets/libraries to identify potent molecules. In the present study, we have
carried out ab initio quantum chemical studies, including relativistic effects followed by molecular
docking with the SARS-CoV-2 protease target by employing a tailor-made library consisting of
molecular analogs of Resveratrol, a natural bioflavonoid.
Results: The derived docking results were validated with ab initio quantum computations that included
both density functional level (DFT) and Moller-Plesset second order perturbation theories
(MP2). We found to be that Resveratrol and its analogs (R8 and R17) bind to the SARS-CoV-2
protease target. In addition to this, the computed IR spectrum is found in agreement with the reported
experimental spectra for Resveratrol complexes and thus validates the modeling and reliability
of proposed geometries. The solvation energies in the aqueous phase obtained using enhanced augcc-
pVTZ basis sets confirm enhancement of bioavailability for Resveratrol through piperine, a natural
Conclusion: The potential of the natural bioflavonoid Resveratrol and its analogs to be investigated
through in vivo and in vitro SARS-CoV-2 protease models is concluded. The study investigated
the potential of natural polyphenols as promising anti-viral therapeutics.