In Silico Molecular Docking Studies and Design of Dengue Virus Inhibitors

Abstract

Dengue fever is an infectious tropical disease which is caused by the dengue virus. Dengue infection is one of the most significant mosquito-transmitted infections which is common in >100 tropical and subtropical countries. Dengue fever is becoming a serious health risk these days and it shortly needs treatment against the increasing problems around the globe and the existence of resisting mutants of dengue virus. In this study the problem of designing an anti-dengue drug with more effectiveness has been solved by using computer aided drug designing. Computer-aided drug design (CADD) entails the use of biochemical information of ligand- receptor interaction sequentially to hypothesize the drugs refinements. Docking of selected ligands, having anti- dengue activity with the active-site of protein 2FOM, was done to find the biochemical information. Docking interactions were interpreted in the form of hydrogen bonding, hydrophobic and ionic interactions. On the basis of this interaction analysis and IC50 value, one of the ligand was recognized as 'lead compound'. Seven analogues of the lead compound were designed and docked with the active site of protein. Interactions of the analogues with the active site of 2FOM protein were analyzed. On the basis of activity and high binding interactions these compounds will be suggested for clinical testing and synthesis in laboratory as a future plan. Keywords: Anti-Dengue Agents; Lead Compound; Computer Aided Drug Design(CADD); IC50; Ligand- Receptor Interactions; Analogs; DENV-proteases like NS3/NS2B protease receptor (2FOM); Quantitative Structure Activity Relationship (QSAR). Abbreviations: DENV=Dengue Virus; ADE=Antibody-Dependent Enhancement; CADD= Computer Aided Drug Design; QSAR= Quantitative Structure Activity Relationship; IC50= The half maximal inhibitory concentration.