NS3 Helicase Inhibitors
Dr. Boguszewska-Chachulska notes that the nonstructural protein 3 (NS3) is a highly promising target for anti-HCV therapy because of its multiple enzymatic activities, such as RNA-stimulated nucleoside triphosphatase, RNA helicase, and serine protease. The RNA helicase, the C-terminal part of NS3, is necessary for the replication of the viral RNA.
“I am mostly focused on HCV helicase inhibitors. Our group is looking for the most active and least cytotoxic, and then analyzing thoroughly their activities, such as interactions with the helicase protein,” comments Dr. Boguszewska-Chachulska, who will discuss helicase inhibitors as potential components of a multidrug therapy against HCV at the meeting.
Helicase inhibitors were identified by an in vitro fluorometric assay of helicase activity developed by Dr. Boguszewska-Chachulska’s team. “We subsequently demonstrated high antiviral activities in the HCV subgenomic replicon system, together with low cytotoxicity, for compounds belonging to three different groups: acridone-4-carboxylic derivatives (EC50 in the range of 9–10 uM), amidinoanthracyclines (EC50 in the range of 0.01–0.14 uM), and tropolone derivatives (EC50 corresponding to 30–46 uM),” she explains.