s Molecular Insights into Resveratrol and Its Analogs as SARS-CoV-2 (COVID-19) Protease Inhibitors

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 alkaloid. 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.