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

The Open Bioinformatics Journal 11 Mar 2024 RESEARCH ARTICLE DOI: 10.2174/0118750362284177240304055831



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.


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.


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.


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.


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.


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.

Keywords: SARS-CoV-2, Spike protein, Antiviral bioactive compounds, In silico approach, Antivirinformatics, Ligand based.
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