Biochemistry (Moscow)

, Volume 71, Issue 9, pp 1021–1026 | Cite as

Hepatitis C virus RNA-dependent RNA polymerase: Study on the inhibition mechanism by pyrogallol derivatives

  • M. V. Kozlov
  • K. M. Polyakov
  • A. V. Ivanov
  • S. E. Filippova
  • A. O. Kuzyakin
  • V. L. Tunitskaya
  • S. N. Kochetkov


Pyrogallol reversibly and noncompetitively inhibits the activity of the hepatitis C RNA-dependent RNA polyme rase. Based on molecular modeling of the inhibitor binding in the active site of the enzyme, the inhibition was suggested to be realized via chelation of two magnesium cations involved in the catalysis at the stage of the phosphoryl residue transfer. The proposed model allowed us to purposefully synthesize new derivatives with higher inhibitory capacity.

Key words

hepatitis C virus RNA-dependent RNA polymerase pyrogallol derivatives inhibition mechanism molecular modeling 



2,4-dioxo-4-phenylbutanoic acid


4-[2-(3-cyanopropoxy)phenyl]-2,4-dioxobutanoic acid




cyanoacetylhydrazone 5-formylpyrogallol




hepatitis C virus


nucleoside triphosphate


RNA-dependent RNA polymerase


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Copyright information

© Pleiades Publishing, Inc. 2006

Authors and Affiliations

  • M. V. Kozlov
    • 1
  • K. M. Polyakov
    • 1
  • A. V. Ivanov
    • 1
  • S. E. Filippova
    • 1
  • A. O. Kuzyakin
    • 1
  • V. L. Tunitskaya
    • 1
  • S. N. Kochetkov
    • 1
  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia

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