The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (M pro ). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and M pro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in M pro -unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the M pro -ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 M pro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential.
【저자키워드】 SARS-CoV-2, in silico, isoquercetin, 10-hydroxyaloin A, drugable targets, 【초록키워드】 Efficacy, spike, molecular docking, drug, molecular dynamics, protease, in vitro, anti-SARS-CoV-2, principal component analysis, MD simulation, binding site, free energy, MPro, RdRP, RNA-dependent RNA polymerase, target, molecular, plant, in vivo, inhibitor, isoquercetin, SARS-CoV-2 spike, Amino acid, RMSD, RMSF, Analysis, lead, Principal component, active site, hydrogen, (RdRp), Gibbs free energy, complex, experimental validation, Compound, M pro, Cys145, docking score, target protein, parameter, physiochemical properties, amino acid residue, stable complex, bind, Result, responsible, was performed, screened, complexes, the Spike, physiochemical property, the SARS-CoV-2, 【제목키워드】 Dynamics, Simulation, target, identification, natural, Against,