Abstract
Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting M pro protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ≈ 100) against SARS-Cov-2 M pro protein. Molecular docking studies revealed that certain W. somnifera compounds exhibit superior binding potential (-6.16 to -12.27 kcal/mol) compared to the standard inhibitors (-2.55 to -6.16 kcal/mol) including nelfinavir and lopinavir. The non-characteristic compounds (quercetin-3-rutinoside-7-glucoside, rutin and isochlorogenic acid B) exhibited higher inhibitory potential in comparison to characteristic W. somnifera compounds withanolide and withanone. Molecular dynamics (MD) simulation studies of the complex for 100 ns confirm favorable and stable binding of the lead molecule. The MMPBSA calculation of the last 10 ns of the protein-ligand complex trajectory exhibited stable binding of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 M pro . Taken together, the study demonstrates that the non-characteristic compounds present in W. somnifera possess enhanced potential to bind SARS-Cov-2 M pro active site. We further recommend in vitro and in vivo experimentation to validate the anti-SARS-CoV-2 potential of these lead molecules.
Keywords: Antiviral; In silico studies; M(pro); Phytochemicals; SARS-CoV-2; Withania somnifera.
【저자키워드】 SARS-CoV-2, Antiviral, M(pro), phytochemicals, In silico studies, Withania somnifera, 【초록키워드】 coronavirus, Antiviral, Lopinavir, quercetin, molecular dynamics, protease, in vitro, rutin, anti-SARS-CoV-2, Protein, pathogen, Antiviral agents, drug target, trajectory, Pathogens, nelfinavir, in vivo, antiviral agent, inhibitor, characteristic, binding, active site, glucoside, complex, Molecular docking study, Compound, M pro, effort, silico studies, molecular docking studies, simulation studies, contagious, inhibitory, Simulation study, Affect, effective, rutinoside, withanolide, exhibited, protein-ligand, 【제목키워드】 molecular docking, MD simulation, phytochemical, inhibit SARS-CoV-2,