Molecular Docking Based Screening of Plant Flavonoids as Dengue NS1 Inhibitors

Abstract

Dengue infection has turned into a serious health concern globally due to its high morbidity rate and a high possibility of increase in its mortality rate on the account of unavailability of any proper treatment for severe dengue infection. The situation demands an urgent development of efficient and practicable treatment to deal with Dengue virus (DENV). Flavonoids, a class of phytochemicals present in medicinal plants, possess anti-viral activity and can be strong drug candidates against viruses. NS1 glycoprotein of Dengue virus is involved in its RNA replication and can be a strong target for screening of drugs against this virus. Current study focuses on the identification of flavonoids which can block Asn-130 glycosylation site of Dengue virus NS1 to inhibit viral replication as glycosylation of NS1 is required for its biological functioning. Molecular docking approach was used in this study and the results revealed that flavonoids have strong potential interactions with active site of NS1. Six flavonoids (Deoxycalyxin A; 3,5,7,3',4'-pentahydroxyflavonol-3-O-beta-D-galactopyranoside; (3R)-3',8-Dihydroxyvestitol; Sanggenon O; Epigallocatechin gallate; Chamaejasmin) blocked the Asn-130 glycosylation site of NS1 and could be able to inhibit the viral replication. It can be concluded from this study that these flavonoids could serve as antiviral drugs for dengue infections. Further in-vitro analyses are required to confirm their efficacy and to evaluate their drug potency.

A Computational Approach on Understanding Structural Interactions of Envelope Protein of Dengue Virus Bound With Squalene, a Prototype Anti-Viral Compound

“…Moreover, the research studies also rationalized that the novel ribavirin analogs presumably may not cause hemolytic anemia to the patients supposed to administrate them as the compounds showed weak affinities towards the JAK2 enzyme playing essential roles in erythropoiesis. Qamar et al [15] postulate through a computational approach that flavanoids (Deoxycalyxin A, 3,5,7,3',4'pentahydroxyflavonol-3-O-beta-D-galactopyranoside, (3R)-3',8-Dihydroxyvestitol, Sanggenon O, Epigallocatechin gallate and Chamaejasmine) inhibited the NS1 (by blocking through the Asparagin 130 glycosylation site), an important regulatory element in the replication processes of dengue viruses. Ariza et al [16] showed that molecular dockings between curcumin and RdRp domain of the NS5 protein, also a key element in the viral replication, with a binding energy of-6.2 Kcal/mol.…”

Peptide vaccine against chikungunya virus: immuno-informatics combined with molecular docking approach

“…Peptide models (antigenic determinants) were docked against their respective HLA-B7 allele through Molecular Operating Environment (MOE) tool to analyze their inhibitory potential. Protocol for molecular docking using MOE has already been reported in various studies involving the antiviral discovery against dengue non-structural proteases [ 30 – 32 ]. Docking protocol used in those studies involves removal of already bound peptide, protonation, energy minimization followed by removal of water molecules.…”

Target Identification Using Homopharma and Network-Based Methods for Predicting Compounds Against Dengue Virus-Infected Cells

“…The NS1 protein is involved in several functions throughout the viral life cycle and immune evasion and can be used for DENV detection. Some studies have reported that the NS1 protein can serve as a drug target for DENV [54,55]. However, although the binding region of this protein has been predicted using computational tools, this has not been experimentally confirmed.…”