Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study

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.

Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach

“…Compounds present in Azadirachta indica (n=93) and Aloe vera (L.) (n=37) were searched from different sources such as Science Direct, PubMed Central Google Scholar, Web of Science, PubMed, Scopus, Semantic Scholar, Medline, and Google Scholar (Kushwaha et al, 2021b). Marvin Sketch software (https://chemaxon.com/products/marvin) was used to prepare the structures of phytochemicals.…”

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study

“…Literature showed that, MM-PBSA method could effectively estimate the fee energy of binding of the docked complexes. Although it requires high computational cost, it can still provide near accurate result than the conventional molecular docking technique [ 43 , 44 ]. The results showed that when compared with the control drug Chloroquine (ΔG binding −90.89 ± 12.33 KJ mol −1 ), Curcumin had a very high binding affinity (ΔG -180.04 ± 15.16 KJ mol −1 ) towards the receptor protein Omicron S. Further, this observation was supported by higher contribution of other energy terms namely ΔG Non polar, ΔG Electrostatic and ΔG Van der Waal as shown in Table 4 .…”

Evaluation of tea (Camellia sinensis L.) phytochemicals as multi-disease modulators, a multidimensional in silico strategy with the combinations of network pharmacology, pharmacophore analysis, statistics and molecular docking

“…The computer-assisted molecular docking simulation tool is very useful in computational biology study to determine the accuracy and stability of the docked complex in a near-native physiological environment. Kushwaha et al [ 111 ] recently exhibited the binding stability of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 M pro by using MD simulation tool. Similarly, Islam et al [ 112 ] use MD simulation tool to evaluate the docking potential of the selected phytochemicals against the main protease of SARS-CoV-2.…”