Antiviral Agents against Flavivirus Protease: Prospect and Future Direction

Flaviviruses cause a significant amount of mortality and morbidity, especially in regions where they are endemic. A recent example is the outbreak of Zika virus throughout the world. Development of antiviral drugs against different viral targets is as important as the development of vaccines. During viral replication, a single polyprotein precursor (PP) is produced and further cleaved into individual proteins by a viral NS2B-NS3 protease complex together with host proteases. Flavivirus protease is one of the most attractive targets for development of therapeutic antivirals because it is essential for viral PP processing, leading to active viral proteins. In this review, we have summarized recent development in drug discovery targeting the NS2B-NS3 protease of flaviviruses, especially Zika, dengue, and West Nile viruses.