New non-nucleoside inhibitors of hepatitis C virus RNA-dependent RNA polymerase.
Recombinant RNA-dependent RNA polymerase of hepatitis C virus was purified using a bacterial expression system (Escherichia coli). The system for enzyme activity detection was optimized. The maximum activity was achieved when the reaction was carried out at 30 degrees C in the presence of 3 mM Mg2+ or 0.75 mM Mn2+. Among alpha- and beta-pyrogallaldehydes, effective inhibitors were found. It was shown that they acted at the primer elongation stage, and their binding to the protein is reversible.
Ivanov
A V
AV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. aivanov@yandex.ru
Kozlov
M V
MV
Kuzyakin
A O
AO
Kostyuk
D A
DA
Tunitskaya
V L
VL
Kochetkov
S N
SN
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology*; D015394:Molecular Structure; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase