Structure and Ligand-based In Silico Studies towards the Natural Inhibitors against Receptor Recognition Spike Protein of SARS-CoV-2

Aim In silico exploration, identification, and therapeutic potential of natural bioactive compounds as antiviral agents are compared with established FDA-approved antiviral drugs. The main aim of this study is to harness the best of plant-based bioactive compounds in the ongoing battle against viral infections. Objectives To investigate the specific amino acid residues within the spike (S) protein of SARS-CoV-2 that exhibit active sites. Furthermore, our objective is to evaluate the efficacy of molecular interactions between the active site residues of spike (S) protein of SARS-2 with FDA-approved drugs and screened bioactive compounds as a potential therapeutic antiviral agent employing in silico approach. Background The ongoing global pandemic, attributed to the SARS-CoV-2 virus, commonly known as severe acute respiratory syndrome, continues to spread, giving rise to various emerging variants. These variants, identified as variants of concern or interest (VOC/I), revealed a significant threat to global health, contributing to the severity of the catastrophe. Methods We explored how natural bioactive compounds derived from plants and certain FDA-approved drugs interact with the spike (S) protein of the virus. To do this, we employed techniques called molecular docking and molecular dynamics simulation (MD & MD Simulation) to evaluate the antiviral potential of screened bioactive compounds against spike (S) protein. Results In this study, Withanolide B and A bioactive compounds revealed the best molecular interaction (binding affinity) with spike (S) protein the SARS-CoV-2, with binding energies of -8.6 and -8.3 kcal/mol, respectively. Conclusion Unlike usually prescribed drugs, Withanolide B & A, derived from Withania somnifera, commonly known as ashwagandha, were found to be potential inhibitors of the spike (S) protein. This study indicates and emphasizes the promising role of natural compounds in the combat against COVID-19.