Small Molecule Drug Discovery for Dengue and West Nile Viruses: Applying Experience from Hepatitis C Virus

There are currently no specific treatments for infection with Dengue virus (DENV) and West Nile Virus (WNV). Drug-discovery programs are underway for both viruses, but as yet no small molecules have advanced to clinical trials. Hepatitis C virus (HCV) is a related flavivirus that has been the focus of intense drug discovery efforts for the last two decades. Many approaches currently being pursued for DENV and WNV have been previously attempted for HCV with varying degrees of success. The experience with HCV may direct DENV and WNV efforts towards approaches with the best chance of success. Based on experience with HCV, the viral polymerase and protease are attractive targets to focus on since these have been most successful to date. Cell-based phenotypic screening may also yield attractive inhibitors. The helicase and methyltransferase enzymes are likely to prove difficult targets and host target approaches are fraught with safety concerns.