Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study

Abstract

The spread of the Dengue virus over the world, as well as multiple outbreaks of different serotypes, has resulted in a large number of deaths and a medical emergency, as no viable medications to treat Dengue virus patients have yet been found. In this paper, we provide an in silico virtual screening and molecular dynamics-based analysis to uncover efficient Dengue infection inhibitors. Based on a Google search and literature mining, a large phytochemical library was generated and employed as ligand molecules. In this investigation, the protein target NS2B/NS3 from Dengue was employed, and around 27 compounds were evaluated in a docking study. Phellodendroside (−63 kcal/mole), quercimeritrin (−59.5 kcal/mole), and quercetin-7-O-rutinoside (−54.1 kcal/mole) were chosen based on their binding free energy in MM-GBSA. The tested compounds generated numerous interactions at Lys74, Asn152, and Gln167 residues in the active regions of NS2B/NS3, which is needed for the protein’s inhibition. As a result, the stable mode of docked complexes is defined by various descriptors from molecular dynamics simulations, such as RMSD, SASA, Rg, RMSF, and hydrogen bond. The pharmacological properties of the compounds were also investigated, and no toxicity was found in computational ADMET properties calculations. As a result, this computational analysis may aid fellow researchers in developing innovative Dengue virus inhibitors.

Exploring the inhibitory potential of Nigella sativa against dengue virus NS2B/NS3 protease and NS5 polymerase using computational approaches

“…66 Based on antiviral phytochemicals, the active site residues of the dengue NS2B/NS3 protease (Table 7) Lys73, Lys74, Leu76, Trp83, His51, Phe130, Leu128, Leu85, Glu88, Gly87, Ile165, Ala166, Ala164, Asn152, and Asn167 were observed to be involved in hydrophobic and hydrogen bond formation. 12,67 Taraxerol (−9.1 kcal mol −1 ) interacted with Pro132, His51, Leu128, Tyr161, while astragalin showed binding affinity of −8.0 kcal mol −1 and interacted with residues Asn167, Trp89, Gly87, Ala166, Val147, Glu88, Ile165, Asn152, Leu86, Lys74. β-Sitosterol (−8.3 kcal mol −1 ), campesterol (8.1 kcal mol −1 ), and nigellidine (−7.3 kcal mol −1 ), each interacted actively with four amino acid residues of NS2B/NS3.…”

Computational Investigations of Traditional Chinese Medicinal Compounds against the Omicron Variant of SARS-CoV-2 to Rescue the Host Immune System

“…The most generally utilized strategy in many related studies is to evaluate the strength of small molecule binding by employing the binding free energy (BFE) approach [51][52][53][54]. We also adopted the MMPBSA.py script to compute the binding free energy of the proteinligand complexes by evaluating 2500 snapshots, keeping in mind the relevance of this strategy in re-ranking the binding conformations.…”