Biogenic Polyamines Spermine and Spermidine Activate RNA Polymerase and Inhibit RNA Helicase of Hepatitis C Virus

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A. N. Korovina^#, V. L. Tunitskaya^#, M. A. Khomutov, A. R. Simonian, A. R. Khomutov, A. V. Ivanov^*, and S. N. Kochetkov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (499) 135-1405; E-mail: aivanov@yandex.ru; aivanov@eimb.ru

^# Contributed equally to this work.

^* To whom correspondence should be addressed.

Received April 25, 2012

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Influence of the biogenic polyamines spermine, spermidine, and putrescine as well as their derivatives on the replication enzymes of hepatitis C virus (HCV) was investigated. It was found that spermine and spermidine activate HCV RNA-dependent RNA polymerase (NS5B protein). This effect was not caused by the stabilization of the enzyme or by competition with template–primer complex, but rather it was due to achievement of true maximum velocity V_max. Natural polyamines and their derivatives effectively inhibited the helicase reaction catalyzed by another enzyme of HCV replication – helicase/NTPase (NS3 protein). However, these compounds affected neither the NTPase reaction nor its activation by polynucleotides. Activation of the HCV RNA polymerase and inhibition of the viral helicase were shown at physiological concentrations of the polyamines. These data suggest that biogenic polyamines may cause differently directed effects on the replication of the HCV genome in an infected cell.

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KEY WORDS: polyamines, spermine, spermidine, analogs, hepatitis C virus, RNA polymerase, helicase

DOI: 10.1134/S0006297912100094

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