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Inhibition of the helicase activity of HCV NTPase-helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide-5'-triphosphate [ribavirin-TP]

100%

Borowski P., Lang M., Niebuhr A., Haag A., Schmitz H., Schulze zur Wiesch J., Choe J., Siwecka M. A., Kulikowski T.

Acta Biochimica Polonica

2001

tom 48

nr 3

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.

NTPase-helicase of Flaviviridae: inhibitors and inhibition of the enzyme

80%

Borowski P., Niebuhr A., Schmitz H., Hosmane R. S., Bretner M., Siwecka M. A., Kulikowski T.

Acta Biochimica Polonica

2002

tom 49

nr 3

RNA nucleoside triphosphatases (NTPase)/helicases represent a large family of proteins that are ubiquitously distributed over a wide range of organisms. The enzymes play essential role in cell development and differentiation, and some of them are involved in transcription and replication of viral single-stranded RNA genomes. The enzymatic activities of a NTPase/helicase were also detected in the carboxyl-terminal non-structural protein 3 (NS3) of members of the Flaviviridae family. The crucial role of the enzyme for the virus life cycle was demonstrated in knock out experiments and by using NTPase/helicase specific inhibitors. This makes the enzyme an attractive target for development of Flaviviridae-specific antiviral therapies. This review will sum-marize our knowledge about the function and structure of the enzyme, update the spectrum of inhibitors of the enzymatic activities of the NTPase/helicase and describe the different mechanisms by which the compounds act. Some of the compounds reviewed herein could show potential utility as antiviral agents against Flaviviridae viruses.

Ograniczanie wyników

2 Acta Biochimica Polonica

2 Borowski P.

2 Kulikowski T.

2 Niebuhr A.

2 Schmitz H.

2 Siwecka M. A.

1 Bretner M.

1 Choe J.

1 Haag A.

1 Hosmane R. S.

1 Lang M.

1 Schulze zur Wiesch J.

1 2002

1 2001

Wyniki wyszukiwania

Inhibition of the helicase activity of HCV NTPase-helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide-5'-triphosphate [ribavirin-TP]

NTPase-helicase of Flaviviridae: inhibitors and inhibition of the enzyme