In silico identification of novel allosteric inhibitors of Dengue virus NS2B/NS3 serine protease

Abstract

Although dengue is a disease that affects more than 100 countries and puts almost 400 million lives at risk each year, there is no approved antiviral in the treatment of this pathology. In this context, proteases are potential biological targets since they are essential in the replication process of this virus. In this study, a library of more than 3,000 structures was used to explore the allosteric inhibition of the NS2B/NS3 protease complex using consensual docking techniques. The results show four best ranked structures that were selected for molecular dynamics and free energy simulations. The present analysis corroborates with other studies (experimental and theoretical) presented in the literature. Thus, the computational approach used here proved to be useful for planning new inhibitors in the combat against Dengue disease.

Keywords

• ns2b/ns3pro
• consensual docking
• molecular dynamics
• binding free energy calculations