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International Journal of Pharmacology

Year: 2016 | Volume: 12 | Issue: 6 | Page No.: 621-632
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Authors

Muhammad Tahir ul Qamar

Saleha Kiran

Usman Ali Ashfaq

Muhammad Rizwan Javed

Farooq Anwar

Muhammad Amjad Ali

Anwar ul Hassan Gilani

Keywords

Research Article

Discovery of Novel Dengue NS2B/NS3 Protease Inhibitors Using Pharmacophore Modeling and Molecular Docking Based Virtual Screening of the ZINC Database

Muhammad Tahir ul Qamar
Center of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture (UAF), 38040 Faisalabad, Pakistan
Saleha Kiran
Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), 38000 Faisalabad, Pakistan
Usman Ali Ashfaq
Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), 38000 Faisalabad, Pakistan
Muhammad Rizwan Javed
Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), 38000 Faisalabad, Pakistan
Farooq Anwar
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, 11942 Al-Kharij, Saudi Arabia
Muhammad Amjad Ali
Department of Plant Pathology, University of Agriculture Faisalabad (UAF), 38040 Faisalabad, Pakistan
Anwar ul Hassan Gilani
Department of Biological and Biomedical Sciences, Aga Khan University Medical College, 74800 Karachi, Pakistan
Background: Dengue, a vector borne disease has become a crucial health concern globally. The search for a suitable dengue vaccine has been going on for the last few decades due to unavailability of any effective treatment. An efficient medication strategy is required to overcome the devastating effects of dengue. Now, computational biology has emerged as a novel tool to improve the domain of computer aided drug designing. The present study reports a complex-based pharmacophore computational modeling that elucidates important pharmacophoric features helpful for the inhibition of protease activity of NS2B/NS3 protein of Dengue Virus (DV). Materials and Methods: A seven featured pharmacophore model of DV NS2B/NS3 protease has been developed via crystal structure of NS2B/NS3 protease and its inhibitor complex in Molecular Operating Environment (MOE) pharmacophore constructing tool. The developed pharmacophore model was validated by a test database of the published inhibitors. Validated pharmacophore model was then used to virtually screen the potential compounds from ZINC database. The screened compounds were filtered by Lipinski’s rule of five and further evaluated through molecular docking studies. The results of docking and interaction studies were validated through binding affinity analysis and ADMET profiling. Results: Six hits (ZINC ID’s: 75163069, 59170698, 06395655, 32933073, 13728171 and 65395833) of different scaffolds having interactions with important active site residues (His51, Asp75, Ser135) were predicted. Conclusion: It can be concluded from the finding of the present study that predicted hits could serve as potential candidates to act as starting point in the development of novel and potent NS2B/NS3 protease inhibitors. The present modeling explores the significant role of the predicted hits towards blocking the replication of DV.
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How to cite this article

Muhammad Tahir ul Qamar, Saleha Kiran, Usman Ali Ashfaq, Muhammad Rizwan Javed, Farooq Anwar, Muhammad Amjad Ali and Anwar ul Hassan Gilani, 2016. Discovery of Novel Dengue NS2B/NS3 Protease Inhibitors Using Pharmacophore Modeling and Molecular Docking Based Virtual Screening of the ZINC Database. International Journal of Pharmacology, 12: 621-632.

DOI: 10.3923/ijp.2016.621.632

URL: https://scialert.net/abstract/?doi=ijp.2016.621.632

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