GENOMES TO HITS IN SILICO – TOWARDS THE DISCOVERY OF ANTIVIRAL INHIBITORS FOR NS1, NS3 AND NS5 FROM DENGUE

Abstract

ABSTRACT Dengue is an ignored disease which a one is the cause of 25 a to 100 million infections per a year and 22000 a deaths a every year in a the regions where it a is common. Despite the a great efforts invested in the a research and study for a dengue treatments, there a is still no vaccine or antiviral a drug has reached in the a market, and the disease a treatment and cure is a limited to supportive care. a Among all the strategies a which are used in the search a for the vaccine and for development a of an antiviral drug against a dengue, the most successful approach a for treating the dengue is inhibiting a the viral enzymes. Making a truly effective a dengue vaccine has proven a difficult because of a phenomenon a called antibody dependent a enhancement. It is very difficult a to create a vaccine which is a used against all four a type of dengue virus and can a protect people In today’s scenario a biological information are rich but a functional knowledge a are poor, so challenges a are grand. These challenges a includes the functional a annotation of the genes a present in whole genome, a detection of the druggable targets a and calculation a of three a -dimensional structures of the a druggable protein targets a which can be done from a the a information of their amino a acid sequences and arriving at a lead compounds from the a hits for these targets. We a propose here a a “Genome to Hits In Silico” strategy and illustrate it a on Dengue virus (DENV). a “Genome to hits” is a novel pathway a incorporating a series of steps a such as gene prediction, a protein tertiary structure determination, a active a site identification, hit molecule a generation, docking and scoring a of hits to arrive at lead compounds. a The current state of the art for a each of the steps in the pathway a is high-lighted and the a feasibility of creating an automated a genome to hits assembly a line is discussed. So best way a to design antiviral is a inhibiting the viral enzymes. a NS1, has been associated with a a role in protective immunity. a NS3 is a protease and a a helicase, whereas NS5 is the RNA polymerase a a in charge of viral RNA replication. a NS3 (non-structural 3) and a NS5 carry out all the enzymatic a activities needed for a polyprotein processing and a genome replication