Antiviral phytochemicals as potent inhibitors against NS3 protease of dengue virus

Rahman, Mahbubur; Biswas, Sourav; Islam, Kazi Jahidul; Paul, Archi Sundar; Mahato, Shiplob Kumar; Ali, A.; Halim, Mohammad A.

doi:10.1016/j.compbiomed.2021.104492

Cited by 29 publications

(14 citation statements)

References 48 publications

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“… All values are given in kcal/mol a Components: van der Waals energy ( E vdW ), electrostatic energy in the gas phase ( E ele ), polar solvation energy (Δ G pol ), non-polar solvation energy (Δ G non-pol ) and free energy of binding from covalent binding (Δ G covalent ) b Data obtained from Bharadwaj et al[ 66 ] c Data obtained from Hariono et al[ 12 ] d Data obtained from Rahman et al[ 67 ] …”

Section: Resultsmentioning

confidence: 99%

Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies

et al. 2022

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Dengue fever has been a global health concern. Mitigation is a challenging problem due to non-availability of workable treatments. The most difficult objective is to design a perfect anti-dengue agent capable of inhibiting infections caused by all four serotypes. Various tactics have been employed in the past to discover dengue antivirals, including screening of chemical compounds against dengue virus enzymes. The objective of the current study is to investigate phytocompounds as anti-dengue remedies that target the non-structural 2B and non-structural 3 protease (NS2B-NS3 pro ), a possible therapeutic target for dengue fever. Initially, 300 + antiviral phytocompounds were collected from Duke’s phytochemical and ethnobotanical database and 30 phytocompounds with anti-dengue properties were identified from previously reported studies, which were virtually screened against NS2B-NS3 pro using molecular docking and toxicity evaluation. The top five most screened ligands were naringin, hesperidin, gossypol, maslinic acid and rhodiolin with binding affinities of − 8.7 kcal/mol, − 8.5 kcal/mol, − 8.5 kcal/mol, − 8.5 kcal/mol and − 8.1 kcal/mol, respectively. The finest docked compounds complexed with NS2B-NS3 pro were subjected for molecular dynamics (MD) simulations and binding free energy estimations through molecular mechanics generalized born surface area–based calculations. The results of the study are intriguing in the context of computer-aided screening and the binding affinities of the phytocompounds, proposing maslinic acid (MAS) as a potent bioactive antiviral for the development of phytocompound-based anti-dengue agent. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00894-022-05355-w.

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Section: Resultsmentioning

confidence: 99%

Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies

et al. 2022

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“…Bioflavonoids extracted from Azadirachta indica, such as rutin, hyperoside, kaempferol-3- O -rutinoside, and epicatechin, interacted with the Asn152 residue of the NS3 protease active site [ 45 ]. Lys74, Leu76, Trp83, Leu85, Glu88, Ile165, Ala166, and Asn167 active site residues of the dengue NS2B/NS3 protease were found to be involved in hydrophobic and hydrogen bond formation in a recent study based on antiviral phytochemicals [ 46 ]. Similar interactions were also found for a few amino acid residues in the dengue NS2B/NS3 protease active site (Lys74, Asn152, and Gln167) in several experimentally tested synthetic compounds [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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“… 66 Dengue virus, a mosquito-borne flavivirus, may cause dengue fever or dengue shock syndrome, which might be associated with the encoding of NS3 protease. Screening study has shown that glabridin can be a potential inhibitor against NS3 protease with binding affinity of −7.4 kcal/mol 67 ( Table 1 ). Sodium taurocholate co-transporting polypeptide (NTCP) has been considered as the receptor for hepatitis B virus (HBV) infection.…”

Section: Anti-microorganismmentioning

confidence: 99%

Review on the Diverse Biological Effects of Glabridin

Zhang¹,

Wu²,

Zhong³

et al. 2023

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Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/β-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.

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Antiviral phytochemicals as potent inhibitors against NS3 protease of dengue virus

Cited by 29 publications

References 48 publications

Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies

Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies

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

Review on the Diverse Biological Effects of Glabridin

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