In silicoscreening and molecular dynamics of phytochemicals from Indian cuisine against SARS-CoV-2 M^Pro

Abstract

SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 M Pro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ! À8.0 kcal/mol were selected to understand their interaction with M Pro. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 M Pro. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of M Pro were mediated through the OH, SH, NH 2 and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to M Pro with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.

Docking-Based Evidence for the Potential of ImmunoDefender: A Novel Formulated Essential Oil Blend Incorporating Synergistic Antiviral Bioactive Compounds as Promising Mpro Inhibitors Against SARS-CoV-2

“…Our results demonstrated that the selected bioactive molecules interacted strongly with the Mpro target enzymes, affirming the stability of the target-ligand complex and providing a better association constant [26]. These findings suggest that the electrostatic interactions dominate the non-covalent interaction in the cited ligands, making them efficient in targeting Mpro.…”

An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus

“…Researchers have studied several phytochemicals to target SARS CoV-2 M pro through a similar technique. Rajendran et al (2022) [ 91 ] showed two compounds from Indian cuisine, cinnamtannin B2 and cyanin, could inhibit M pro in silico compared with the control. Similarly, natural compounds like withanoside V, and somniferine were effective against the main protease in a molecular docking experiment [ 92 ].…”

Phytochemical Analysis and Cellular Uptake Study of an Ayurvedic Formulation, Vyaghryadi Kashayam Used in the Clinical Management of COVID-19.

“…Screening of the phytochemicals, as obtained from LC-MS/MS QTOF analysis, revealed that seven phytochemicals that are present in VK have been reported previously for potential activity against SARS-CoV-2. These are 6-gingerol [22], 6-shogoal [22], Diacetoxy-4 -gingerdiol [23], gallic acid [24], magnoflorine [24], solasonine [25] and solamargine [25]. The binding site of these phytochemicals from the previous reports and the plant sources of these are summarised in Table 3.…”