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OJBTM
Online Journal of Bioinformatics©
Volume
13(1):130-143, 2012
Pharmacophore model of Dengue virus RNA dependent RNA polymerase
1PG and Reseach Department of Zoology and Biotechnology, Lady Doak College, Narimedu, Madurai, Tamilnadu,
2Institute of
Computational Biology, Bangalore, 3Schrödinger, Bangalore and 4Department of
Biotechnology, New Delhi, India.
ABSTRACT
Shree T, Asnet JM, Kumar R, Mohan T, Shenbagarathai
R., Pharmacophore model of Dengue virus RNA dependent
RNA polymerase, Online J Bioinform., 13(1):130-143, 2012., The development of a safe and
effective therapy for Dengue Fever is a public health priority at a global
level. Novel inhibitors for the viral RNA dependent RNA polymerase (RdRp), were identified through Pharmacophore
modeling. Using three known inhibitors for RdRp, ribavirin -5'- triphosphate, cytidine-5'-triphosphate and triaryl pyrazoline, a three point
pharmacophore model was generated using Phase. In
order to screen efficient binders of RdRp from a
commercial database (Asinex platinum collection)
containing 150,000 compounds, initial screening was performed using pharmacophore search and the obtained hits were further
screened using docking protocol. Finally after screening with ADME filters,
five compounds with Asinex Id: 71241, 25341, 14859, 5199, 33289 survived. On
comparison of free energies of binding of the obtained hits with the known
actives, the novel compounds showed appreciable free energies of binding (0.095989, 0.095989, 0.095989, 0.820135, -0.01717 kcal/mol
respectively). Hence, these compounds were reported as potential leads
to be optimized into potential drugs after being subjected to in vitro screening.
Keywords: DENV, Molecular docking, prime/MM-GBSA, virtual screening, pharmacophore.