Dengue virus NS4B protein as a target for developing antivirals.

Abstract

Dengue virus is an important pathogen affecting global population while no specific treatment is available against this virus. Effort has been made to develop inhibitors through targeting viral nonstructural proteins such as NS3 and NS5 with enzymatic activities. No potent inhibitors entering clinical studies have been developed so far due to many challenges. The genome of dengue virus encodes four membrane-bound nonstructural proteins which do not possess any enzymatic activities. Studies have shown that the membrane protein-NS4B is a validated target for drug discovery and several NS4B inhibitors exhibited antiviral activities in various assays and entered preclinical studies.. Here, we summarize the recent studies on dengue NS4B protein. The structure and membrane topology of dengue NS4B derived from biochemical and biophysical studies are described. Function of NS4B through protein-protein interactions and some available NS4B inhibitors are summarized. Accumulated studies demonstrated that cell-based assays play important roles in developing NS4B inhibitors. Although the atomic structure of NS4B is not obtained, target-based drug discovery approach become feasible to develop NS4B inhibitors as recombinant NS4B protein is available.