Discovery of novel dengue NS2B/NS3 protease inhibitors using pharmacophore modeling and molecular docking based virtual screening of the ZINC database

Abstract

Background: Dengue, a vector borne disease has become a crucial health concern globally. The search for a suitable dengue vaccine has been devastating effects of dengue. Now, computational biologyhasemerged asa novel tool to improve the domain of computer aided drug designing. 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 studies were validated through binding affinity analysis and ADMET profiling. Results: Six hits (ZINC ID'S: 751630697 591706987 063956557 predicted. Conclusion: It can be concluded from the finding of the present study that predicted hits could serve as potential candidates to act predicted hits towards blocking the replication of DV.