Computational investigations of three main drugs and their comparison with synthesized compounds as potent inhibitors of SARS-CoV-2 main protease (Mpro): DFT, QSAR, molecular docking, and in silico toxicity analysis

Abstract

In this study, we examined five previously synthesized compounds and checked their binding affinity towards the SARS-CoV-2 main protease (M pro ) by molecular docking study, and compared the data with three FDA approved drugs, i.e., Remdesivir, Ivermectine and Hydroxychlorochine. In addition, we have investigated the docking study against the main protease of SARS-CoV-2 (M pro ) by using Autodock 4.2 software package. The results suggested that the investigated compounds have property to bind the active position of the protein as reported in approved drugs. Hence, further experimental studies are required. The formation of intermolecular interactions, negative values of scoring functions, free binding energy and the calculated binding constants confirmed that the studied compounds have significant affinity for the specified biotarget. These studied compounds were passed the drug-likeness criteria as suggested by calculating ADME data by SwissADME server. Moreover, the ADMET properties suggested that the investigated compounds to be orally active compounds in human. Furthermore, density functional computations (DFT) were executed by applying GAUSSIAN 09 suit program. In addition, Quantitative Structure-Activity Relationship (QSAR) was studied by applying HyperChem Professional 8.0.3 program.

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

“…Most of the computational studies aimed at predicting the best molecular docking for SARS-CoV-2 proteins have focused on the use of algorithms based on AutoDock Vina (ADV). ADV has an improved scoring function of the knowledge-based AutoDock (AD) method that uses a variant of X-Score, with an adjustment using PDBbind, and also considering the inter- and intramolecular contributions, its sampling technique is based on the Iterative Local Search global optimizer, in its Broyden - Fletcher - Goldfarb - Shanno variant (BFGS) [ 4 , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] ]. The use of the DockThor server was further proposed, which implements a grid-based method that employs a steady-state genetic algorithm for multiple solutions as a search engine and the MMFF94S force field as the scoring function for pose evaluation.…”

In vitro anti‐bacterial activity and network pharmacology analysis of Sanguisorba officinalis L. against Helicobacter pylori infection

“…As described above, a docking activity pocket was formed to output the docking results by Lamarckian genetic algorithm. Cluster analysis tool was used to select the optimal docking model for analysis, and DS Visualizer 2016 software was used for visual analysis of docking results [ 29 , 30 ].…”

Synthesis, α-Glucosidase Inhibition, α-Amylase Inhibition and Molecular Docking Studies of 3,3-Di(Indolyl)Indolin-2-Ones

“…The docking center was set to be the center of protein and the docking pocket size was set to be large enough to cover the whole protein molecule. The docking results were visualized using Discovery studio (Dassault Systèmes, San Diego) (Mohapatra et al, 2021).…”