Plant-derived compounds effectively inhibit the main protease of SARS-CoV-2: An in silico approach

Abstract

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep literature mining and explored their potential to bind with and inhibit the main protease of SARS-CoV-2. The three most effective phytochemicals Cosmosiine, Pelargonidin-3-O-glucoside, and Cleomiscosin A had binding energies of -8.4, -8.4, and -8.2 kcal/mol, respectively, in the docking analysis. These molecules could bind to Gln189, Glu166, Cys145, His41, and Met165 residues on the active site of the targeted protein, leading to specific inhibition. The pharmacological characteristics and toxicity of these compounds, examined using absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses, revealed no carcinogenicity or toxicity. Furthermore, the complexes were simulated with molecular dynamics for 100 ns to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen profiles from the simulation trajectories. Our analysis validated the rigidity of the docked protein-ligand. Taken together, our computational study findings might help develop potential drugs to combat the main protease of the SARS-CoV-2 and help alleviate the severity of the pandemic.

In silico Screening of Potential SARS-CoV-2 Main Protease Inhibitors from Thymus schimperi

“…Previous studies also reported similar findings to our study. Numerous plant-derived phytochemicals such as curcumin, gartanin, robinetin, 83 amentoflavone, gallocatechin gallate, 84 chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, 85 kaempferol, herbacetin, eugenol, 6-shogaol, 86 triacontane, hexacosane, methyl linoleate, and methyl palmitoleate, 87 cosmosiine, pelargoniding-3- O -glucose, and cleomiscosin 88 formed similar binding patterns while docking with the main protease. Another study also reported that plant-derived phytochemicals including flavan 3-ols (catechins/procyanidins), complex oligomeric procyanidins (procyanidin A3, procyanidin A4, procyanidin A1, and procyanidin B3) exhibited very good binding characteristics like our compounds.…”

Integrated Computational Approaches for Inhibiting Sex Hormone-Binding Globulin in Male Infertility by Screening Potent Phytochemicals

“…Simulations were performed using the Berendsen thermostat, accompanied by fixed pressure and temperature for 100 nanoseconds (ns) [ 61 , 62 ]. The root-mean-square-fluctuation (RMSF), root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond were examined through the simulation trajectory data [ 63 , 64 , 65 , 66 ]. Additionally, using the following equation, the binding free energies of the simulation snapshots were estimated using MM-PBSA (Molecular Mechanics-Poisson Boltzmann Surface Area) techniques.…”

Cell-Free Supernatants (CFSs) from the Culture of Bacillus subtilis Inhibit Pseudomonas sp. Biofilm Formation

“…The simulation was run for 100 ns at a constant temperature and pressure, along with the Berendsen thermostat, and the data of the simulation trajectories were recorded after every 100 ps [38,39]. The data of the simulation trajectories were utilized after the simulation process for the analysis of the root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF), solvent accessible surface area (SASA), and hydrogen bond [40][41][42].…”