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.

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

“… 60 The populace as well as the country’s healthcare system are suffering greatly as a result of the simultaneous load of dengue and COVID-19. 9 , 61 Considering that RNA viruses have high mutation rates, developing vaccines against them is extremely difficult or almost impossible. Novel antiviral medicines generated from plants may be considered as effective alternatives in the fight against this menace to humanity.…”

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.…”

Antimicrobial Activity against Antibiotic-resistant Pathogens and Antioxidant Activity and LCMS/MS Phytochemical Content Analysis of Selected Medicinal Plants

“…The notable compounds identified included levomefolic acid, commonly used as a folate supplement for food fortification; triamterene, a phenolic compound used in the treatment of edema and liver cirrhosis, and as a diuretic; and balapiravir, an example of a direct-acting antiviral that targets both structural and non-structural viral proteins. [75][76][77] Additionally, Threonic acid, a phenolic acid, was identified for its potential to inhibit TNF-α, thus potentially offering benefits in memory preservation. Neosaxitoxin, which is known for its local anesthetic properties, and methyldilazine, which exhibits bactericidal activity against Mycobacterium tuberculosis, were also detected.…”