Biogenic polyamines spermine and spermidine activate RNA polymerase and inhibit RNA helicase of hepatitis C virus

• Published in: Biochemistry (Moscow) Vol. 77; no. 10; pp. 1172 - 1180
• Main Authors: Korovina, A. N., Tunitskaya, V. L., Khomutov, M. A., Simonian, A. R., Khomutov, A. R., Ivanov, A. V., Kochetkov, S. N.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01-10-2012; Springer; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Enzyme Activation - drug effects; Enzymes; Genomics; Hepacivirus - drug effects; Hepacivirus - enzymology; Hepatitis; Hepatitis C virus; Humans; Life Sciences; Microbiology; Polyamines; Putrescine - analogs & derivatives; Putrescine - pharmacology; RNA; RNA Helicases - antagonists & inhibitors; RNA Helicases - metabolism; RNA polymerase; RNA-Dependent RNA Polymerase - chemistry; RNA-Dependent RNA Polymerase - metabolism; Spermidine - analogs & derivatives; Spermidine - pharmacology; Spermine - analogs & derivatives; Spermine - pharmacology; Viral Nonstructural Proteins - drug effects; spermidine; analogs; hepatitis C virus; spermine; RNA polymerase; helicase; polyamines
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297912100094

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.