Abstract
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.
Acknowledgements
We thank Andrew Pannifer, Chris Phillips and Steve Irving for structural comparisons of Dengue virus and Hepatitis C virus RNA-dependent RNA polymerase and protease proteins.
Financial & competing interests disclosure
Potential conflict of interest exists: the authors are employed by and own shares in Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.