Structure-based pharmacophore design and screening for potential inhibitors of E protein of dengue virus as a loom for dengue

ABSTRACT

Dengue virus (DENV) poses a continuous threat worldwide with an estimated 2.5 billion people at the risk of dengueinfection. It was believed to be the infection of the tropical regions, but reports of dengue infection have now extendedand spread around the globe. The dengue E protein is involved in the viral fusion and could thus acts a potentialtarget against dengue virus. In the present study, structure-based pharmacophore design and screening and absorption,distribution, metabolism, excretion, and toxicity (ADMET) analysis using Discovery studio (4.0) was applied toidentify potential hits against the hydrophobic pocket of dengue E protein. The pharmacophore feature of screenedcompounds was further validated and finally three lead compounds were obtained. The pharmacophore model andthe docking study were generated three lead molecules Ophiopoginin D with a binding energy of −146.36 Kcal/mol followed by Calmisttrin D with a binding energy of −118.73 Kcal/mol and BTB 08305 with a binding energy of−99.96 Kcal/mol and exhibited best-fit value. ADMET profile showed that all the three lead molecules are non-toxic,non-carcinogenic, and non-hepatotoxic by in silico study. The compound Calmisttrin D exhibited good blood brainbarrier permeability and human intestinal adsorption, and thus hypothesized to have antiviral activity against denguevirus and so further in vitro and in vivo evaluation is recommended.