Interactions between the hepatitis C virus protein NS3 and polymethylene derivatives of nucleic bases

Nonstructural protein 3 (NS3) of hepatitis C virus plays a key role in the functioning of the virus. NS3 displays three enzymatic activities, namely, protease activity associated with the N-terminal domain, coupled nucleoside triphosphotase (NTPase), and helicase activities, localized to the C-terminal domain. In this work, we studied the effects of various polymethylene derivatives of nucleic bases on the NTPase (by the example of ATPase) and helicase activities of NS3. It was demonstrated that some tested compounds inhibited NS3 helicase activity; however, a considerable part of the compounds activated the NTPase activity of NS3 and several other proteins displaying NTPase or selective ATPase activity. Such ATPase activators have not been earlier described, suggesting an unusual activation mechanism. The activation ability of the tested compounds depended on the ratio of substrate (ATP) and activator concentrations, and reached its maximum at a 1000-fold excess of the substrate. A mechanism of ATPase activation was proposed to explain the observed effects.