Inhibition of the helicase activity of HCV NTPase/helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide-5 '-triphosphate (ribavirin-TP).
In the presented study the ribavirin-TP--an established inhibitor of the NTPase activity of the superfamily NTPase/helicases II--was investigated as an inhibitor of the unwinding activity of the hepatitis C virus (HCV) NTPase/helicase. The kinetics of the reaction revealed that ribavirin-TP reduces the turnover number of the helicase reaction by a mechanism that does not correspond to that of the inhibition of the NTPase activity. Our results suggest that derivatives of ribavirin-TP with enhanced stability towards hydrolytic attack may be effective inhibitors of the enzyme.
Borowski
P
P
Abteilung für Virologie, Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.
Lang
M
M
Niebuhr
A
A
Haag
A
A
Schmitz
H
H
Schulze zur Wiesch
J
J
Choe
J
J
Siwecka
M A
MA
Kulikowski
T
T
D017766:Acid Anhydride Hydrolases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D016174:Hepacivirus / Q000201:enzymology*; D007700:Kinetics; D043583:Nucleoside-Triphosphatase; D009711:Nucleotides / Q000494:pharmacology*; D012254:Ribavirin / Q000494:pharmacology; D013379:Substrate Specificity
D000998:Antiviral Agents; D009711:Nucleotides; D012254:Ribavirin; C037827:ribavirin 5'-triphosphate; D004247:DNA; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D004265:DNA Helicases