Computer-aided drug designing for dengue targeting NS3 helicase

Abstract

The Dengue fever is considered as a “neglected tropical disease” as despite the staggering number of cases every year and significant loss of human and economic resources, a specific antiviral drug is not yet available for humankind. With the advent of global warming, increase in migration and urbanisation worldwide, dengue threat looms large over humanity, highlighting the dire need of an antiviral against the infection. In the present study titled as the “Computer-aided Drug Designing for Dengue targeting NS3 Helicase”, the main objective is to predict inhibitors against the target protein, that is, the Non-Structural protein 3 (NS3) of the Dengue virus. This protein is a multifunctional entity, performing NTPase, protease as well as 5’ RNA-triphosphatase activities. Its major function, however, is to perform unwinding of the single stranded RNA genome of the virus so that it becomes more accessible to the replication machinery, which it performs by deriving energy from ATP. We have performed thorough in-silico research and analysis, ranging from conformational analysis of the target protein, virtual screening, ADMET studies, Molecular Dynamics simulations and post-simulation analysis for structural stability as well as binding energetics, for the target protein in order to predict potential inhibitors. In the results of the various experiments, we have obtained positive findings and discovered three potential compounds against our chosen target protein of the Dengue virus. Two of the compounds are from the Natural Product Activity and Species Source Database, that is, they are of natural origin, while the third molecule comes from DrugBank, a repository of drug molecules approved by the FDA and can be repurposed as a drug against Dengue infection. All the three molecules have been subjected to extensive in-silico research and analysis from which we have produced positive findings that demonstrate their potential as inhibitors against the NS3 Helicase of Dengue virus. The present study is a small effort from our side to the larger cause of combating the dengue infection.