Computational studies of Bridelia retusa phytochemicals for the identification of promising molecules with inhibitory potential against the spike protein and papain-like protease of SARS-CoV-2

Abstract

SARS-CoV-2 is the pathogen responsible for the on-going COVID-19 pandemic. The two proteins namely, spike protein and papain-like protease are mainly responsible for the penetration and transmission of the virus, respectively. The objective of our study was to find the most promising phytoconstituents of Bridelia retusa that can inhibit both the proteins. Molecular docking, protein-ligand interactions, and molecular dynamics (MD) simulation techniques were used in the study. Bepridil and the co-crystal inhibitors of each protein were used as the standards. All the 14 phytoconstituents along with the standard drug and the co-crystal inhibitor of each protein were subjected to molecular docking. Ten compounds showed better binding affinities than the standards against the spike protein and 7 compounds have shown better binding affinities than the standards against papain-like protease protein. From the protein-ligand interactions, a total of 3 out of 10 for the spike protein and 5 out of 7 for the papain-like protease showed better interactions than the standards. An all-atom MD simulations study revealed that (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid formed the most stable complex with both proteins. The in-silico study provides an evidence for (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid as a promising inhibitor of the spike and papain-like protease of SARS-CoV-2. Further investigations such as in-vitro/in-vivo studies are recommended to validate the potency of (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid.

Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (Mpro)

“…In silico screening of several benzoic acid derivatives against the SARS-CoV-2 main protease identified 2,5-dihydroxybenzoic acid as the best potential candidate among the investigated structures [ 70 ]. Another in silico study provided evidence for (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid as a promising inhibitor of the spike and papain-like protease of SARS-CoV-2 [ 71 ]. According to a docking analysis with components of Egyptian propolis or bee glue, a resinous material produced by bees to protect their hives, benzoic acid revealed the lowest ICM scores with four hydrogen bonds with LYS110 and THR111.…”

Phytocompound inhibitors of caspase 3 as beta-cell apoptosis treatment development option: An In-silico approach

“…One of the quickest and most accurate in-silico methods for analyzing the molecular interactions and chemical bonding between a ligand and a protein is molecular docking (41). To observe and analyze the molecular interaction and ligand binding of compounds with studied biomarkers, molecular docking research, and in-vivo studies are often combined (42)(43)(44)(45)(46)(47)(48). This discussion demonstrates the reliability of in-silico drug discovery and development studies, supports and validates the methodology used in the current in-silico study, and supports the notion that the African natural product database contains promising phytocompounds that could have the potential to act as Caspase 3 inhibitor.…”