Nitsche, Christoph2020-02-031867-2450http://hdl.handle.net/1885/200938Proteases from flaviviruses have gained substantial interest as potential drug targets to combat infectious diseases caused by dengue, West Nile, Zika and related viruses. Despite nearly two decades of drug discovery campaigns, promising lead compounds for clinical trials have not yet been identified. The main challenges for successful lead compound development are associated with limited drug-likeness of inhibitors and structural ambiguity of the protease target. This brief review focuses on the available information on the structure of flavivirus proteases and their interactions with inhibitors and attempts to point the way forward for successful identification of future lead compounds.Christoph Nitsche thanks the Alexander von Humboldt Foundation for a Feodor Lynen Fellowship and the Free University of Berlin for a Rising Star Fellowship.20 pagesapplication/pdfen-AU© 2019 International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer NatureflavivirusNS2B-NS3protease inhibitorserine protease2019-02-2610.1007/s12551-019-00508-3