Hepatitis C Virus NS3 Helicase Inhibitors
Craig A. Belon and David N. Frick
from: Hepatitis C: Antiviral Drug Discovery and Development (Edited by: Seng-Lai Tan and Yupeng He). Caister Academic Press, U.K. (2011)
The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is a complex multifunctional enzyme. In addition to processing the viral polyprotein, NS3 functions as a viral helicase capable of separating duplex RNA and DNA in reactions fueled by ATP hydrolysis. A functioning helicase is necessary for HCV replication, showing that the NS3 helicase could be an antiviral drug target. Although early screens for HCV helicase inhibitors yielded few if any antiviral leads, more recent studies have found potent helicase inhibitors that are active against the HCV replicon. Noteworthy HCV helicase inhibitors that are relatively non-toxic to cells and inhibit the HCV replicon include triphenylmethanes, acridones, amidinoantrhracyclines, and a rationally designed substituted pyrrole. Also discussed here are assay systems available for discovering and analyzing HCV helicase inhibitors, which can broadly be grouped into two categories: those that measure helicase-catalyzed hydrolysis of ATP, and those that measure helicase-catalyzed separation of double-stranded nucleic acid substrates read more ...