期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 39, 期 4, 页码 1417-1430出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1734485
关键词
Bioflavonoid; molecular docking; dengue virus; Azadirachta indica; cell viability
The study demonstrates the potential of bioflavonoids from Azadirachta indica against dengue infection, indicating their value in drug development.
Dengue virus (DENV) serine protease enzyme, i.e. NS2B-NS3pro (non-structural protein 2B-non-structural protein 3) has been approved as prime drug target for the drug discovery against dengue infection, because of its essential role in viral replication. This study demonstrates the potential of bioflavonoids from Azadirachta indica against dengue infection using computational and experimental approach. Initially, 49 bioflavonoids reported in Azadirachta indica were collected and virtually screened on the catalytic triad of DENV protease, results in the identification of kaempferol-3-O-rutinoside (-9.555 kcal/mol), rutin (-9.324 kcal/mol), hyperoside (-7.879 kcal/mol), and epicatechin (-7.622 kcal/mol) as potent viral protease inhibitors against reference compound quercetin (-6.94 kcal/mol). Subsequently, these docked complexes were analyzed for the stability via molecular dynamics simulations and free binding energy calculations, suggested the considerable stability of selected bioflavonoids with viral protease. Additionally, density functional theory and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis indicated the least chemical reactivity and considerable medicinal properties, respectively for the screened bioflavonoids by comparison to quercetin. Accordingly, kaempferol 3-O-beta-rutinoside and epicatechin were evaluated at various concentrations for cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) and in vitro antiviral activity (focus forming unit assay) against DENV-2 strain. The antiviral assay showed dose dependent inhibition of DENV-2 infectivity by the selected compounds while maximum 77.7% and 66.2% viral inhibition were recorded for 100 mu M kaempferol 3-O-beta-rutinoside and 1000 mu M epicatechin, respectively without significant cell toxicity. These results suggested the potential of bioflavonoids from Azadirachta indica in the development of effective drug against dengue infection. Communicated by Ramaswamy H. Sarma
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