Chapter 6 - Flavivirus Protease: An Antiviral Target

Abstract

The genus Flavivirus consists of more than 70 members. Many of these viruses, such as dengue virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, and yellow fever virus, cause serious human diseases, such as encephalitis and fatal hemorrhagic fever. Flaviviruses are increasingly gaining attention due to their reemergence in different areas of the world, latest of which is the Zika virus in Brazil. Flaviviral-specific NS3 protease, in association with its cofactor NS2B, is the key enzyme responsible for the proteolytic processing of Flavivirus polyprotein. As NS3 and NS2B protease complex plays a pivotal role in the virus life cycle, therefore this virus-specific protease is an important therapeutic target for antiviral drug discovery. Despite the availability of the structural architecture of NS2B–NS3 protease and its catalytic mechanism specifics, to date, no specific drug is available for the treatment of flaviviral infections. Attempts are being made to target the NS2B–NS3 Flavivirus complex by blocking the potential allosteric sites on the NS3 enzyme for drug development. An overview of the compiled structural and functional aspects of NS2B–NS3 Flavivirus protease, along with the recent drug development against the Flavivirus protease given in this chapter, is intended to benefit future drug discovery to combat the pathogenic flaviviruses.