Structural and functional parameters of the flaviviral protease: a promising antiviral drug target

Flaviviruses have a single-strand, positive-polarity RNA genome that encodes a single polyprotein. The polyprotein is comprised of seven nonstructural (NS) and three structural proteins. The N- and C-terminal parts of NS3 represent the serine protease and the RNA helicase, respectively. The cleavage of the polyprotein by the protease is required to produce the individual viral proteins, which assemble a new viral progeny. Conversely, inactivation of the protease blocks viral infection. Both the protease and the helicase are conserved among flaviviruses. As a result, NS3 is a promising drug target in flaviviral infections. This article examines the West Nile virus NS3 with an emphasis on the structural and functional parameters of the protease, the helicase and their cofactors.