Designing and analysis of a potent bi-functional aptamers that inhibit protease and helicase activities of HCV NS3.

Nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a multi-functional enzyme having protease and helicase activities. NS3 is essential for HCV replication and proliferation. Previously, we obtained RNA aptamers against NS3 protease domain (Protease aptamer; deltaNEO-III and G9-II) and helicase domain (helicase aptamer; #5), and they inhibited the enzyme activities, respectively. We designed and constructed new bi-functional aptamers NEO-35-sX and G925-sX (X: 5-51 nts) by conjugating protease and helicase aptamers via oligo U spacer. Some of them showed 10-fold higher helicase inhibition than helicase aptamer #5 alone.