Targeting the protease of West Nile virus

West Nile virus infections can cause severe neurological symptoms. During the last 25 years, cases have been reported in Asia, North America, Africa, Europe and Australia (Kunjin). No West Nile virus vaccines or specific antiviral therapies are available to date. Various viral proteins and host-cell factors have been evaluated as potential drug targets. The viral protease NS2B-NS3 is among the most promising viral targets. It releases viral proteins from a non-functional polyprotein precursor, making it a critical factor of viral replication. Despite strong efforts, no protease inhibitors have reached clinical trials yet. Substrate-derived peptidomimetics have facilitated structural elucidations of the active protease state, while alternative compounds with increased drug-likeness have recently expanded drug discovery efforts beyond the active site.

Automated summary

West Nile virus infections can cause severe neurological symptoms, but there are currently no vaccines or specific antiviral therapies available. The viral protease NS2B-NS3 is considered a promising target, but protease inhibitors have not yet reached clinical trials. Substrate-derived peptidomimetics have aided in understanding the protease's active state, while new compounds aim to expand drug discovery efforts.