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

Peter Borowski | Zendy; Oliver Mueller | Zendy; Andreas Niebuhr | Zendy; Matthias Kalitzky | Zendy; L H Hwang | Zendy; Herbert Schmitz | Zendy; M. A. Siwecka | Zendy; T Kulikowsk | Zendy

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

Author(s) -

Peter Borowski,

Oliver Mueller,

Andreas Niebuhr,

Matthias Kalitzky,

L H Hwang,

Herbert Schmitz,

M. A. Siwecka,

T Kulikowsk

Publication year - 2000

Publication title -

acta biochimica polonica

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.452

H-Index - 78

eISSN - 1734-154X

pISSN - 0001-527X

DOI - 10.18388/abp.2000_4075

Subject(s) - helicase , virology , chemistry , domain (mathematical analysis) , antiviral therapy , rna helicase a , biology , biochemistry , chronic hepatitis , rna , virus , gene , mathematical analysis , mathematics

To enhance the inhibitory potential of 1-beta-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 microM) as compared to ribavirin (IC50 > 500 microM). 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.

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