Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 35, Issue 13, Pages 2895-2909Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2016.1234416
Keywords
quercetin; dengue; RNA-dependent RNA polymerase; flavonoids; molecular dynamics simulation; binding free energy; non-nucleoside inhibitor
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Funding
- Department of Science and Technology, Ministry of Science and Technology [SR/WOS-A/LS62/2013]
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Dengue is an important public health problem in tropical and subtropical regions of the world. Neither vaccine nor an antiviral medication is available to treat dengue. This insists the need of drug discovery for dengue. In order to find a potent lead molecule, RNA-dependent RNA polymerase which is essential for dengue viral replication is chosen as a drug target. As Quercetin showed antiviral activity against several viruses, quercetin derivatives developed by combinatorial library synthesis and mined from PubChem databases were screened for a potent anti-dengue viral agent. Our study predicted Quercetin 3-(6-(E)-p-coumaroylsophoroside)-7-rhamnoside as a dengue polymerase inhibitor. The results were validated by molecular dynamics simulation studies which reveal water bridges and hydrogen bonds as major contributors for the stability of the polymerase-lead complex. Interactions formed by this compound with residues Trp795, Arg792 and Glu351 are found to be essential for the stability of the polymerase-lead complex. Our study demonstrates Quercetin 3-(6-(E)-p-coumaroylsophoroside)-7-rhamnoside as a potent non-nucleoside inhibitor for dengue polymerase.
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