Docking and QM/MM studies of NS2B-NS3pro inhibitors: A molecular target against the dengue virus

Abstract

Dengue virus (DENV) has been characterized as having great clinical importance in the world, as there is no specific treatment against this virus. The NS2B-NS3pro complex is essential for the replication and maturation of DENV and is a potential pharmacological target. The present study aims to evaluate and understand the interactions and affinities (via molecular docking/AutoDock Vina) of 16 peptidomimetic derivatives applied to a NS2B-NS3pro DENV-2 complex constructed by homology modeling (via SWISS-MODEL). Two compounds were selected as potential inhibitors of this protein complex. In addition, these compounds possess important interactions involving Ser135, Gly169 and Tyr161, which have been described previously to be fundamental to the recognition of inhibitors directed to this receptor. Thus, the involvement of these residues is significant pharmacologically because they may contribute to the inhibitory action of this molecular target against DENV.