Computational Analyses of NS3 Serine Protease of Dengue Virus

Abstract

Dengue virus (DENV), a mosquito-borne Flavivirus, is an emerging global health threat. A number of studies have already revealed that the non-structural NS3 serine protease is required for the maturation of the viral polyprotein and thus is a promising target for the development of antiviral inhibitors. However, the residues and other structural elements that play a role in the enzyme-mediated maturation process of DENV by NS3 have yet to be definitely assigned. Identification of the binding site and the actual environment around the active site pocket are still open to questions. To elucidate the functions of DENV NS3 and in particular, for a better understanding of the active site pocket of the enzyme, a 3D model of DEN2 NS3 serine protease to locate its key catalytic residues has been proposed. From computational comparative analyses of sequences and structures of related NS3 serine proteases of the Flaviviridae family, the charge distribution and electrostatic potential in and around the active site pocket of DEN2-NS3 serine protease have also been predicted. This proposed model would facilitate future studies for better rationalize the environment of the substrate-binding pocket and thus stimulate more rationally designed structure-function studies aimed at elucidating the role of this enzyme in virus maturation.