ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy

Peter Borowski, Oliver Mueller, Andreas Niebuhr, Matthias Kalitzky, Lih Hwa Hwang, Herbert Schmitz, Maria A. Siwecka, Tadeusz Kulikowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


To enhance the inhibitory potential of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) vs hepatitis C virus (HCV) NTPase/helicase, ribavirin-5′-triphosphate (ribavirin-TP) was synthesized and investigated. Ribavirin-TP was prepared with the use of modified Yoshikawa-Ludwig-Mishra-Broom procedure (cf. Mishra & Broom, 1991, J. Chem. Soc., Chem. Commun, 1276-1277) involving phosphorylation of unprotected nucleoside. Kinetic analysis revealed enhanced inhibitory potential of ribavirin-TP (IC50=40 μM) as compared to ribavirin (IC50 > 500 μM). Analysis of the inhibition type by means of graphical methods showed a competitive type of inhibition with respect to ATP. In view of the relatively low specificity towards nucleoside-5′-triphosphates (NTP) of the viral NTPase/helicases, it could not be ruled out that the investigated enzyme hydrolyzed the ribavirin-TP to less potent products. Investigations on non-hydrolysable analogs of ribavirin-TP or ribavirin-5′-diphosphate (ribavirin-DP) are currently under way.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalActa Biochimica Polonica
Issue number1
StatePublished - 2000


  • Enzyme inhibition
  • HCV NTPase/helicase
  • Ribavirin-5′-triphosphate


Dive into the research topics of 'ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy'. Together they form a unique fingerprint.

Cite this