New non-nucleoside inhibitors of hepatitis C virus RNA-dependent RNA polymerase

• Published in: Biochemistry (Moscow) Vol. 69; no. 7; pp. 782 - 788
• Main Authors: Ivanov, A V, Kozlov, M V, Kuzyakin, A O, Kostyuk, D A, Tunitskaya, V L, Kochetkov, S N
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01-07-2004
• Subjects: E coli; Enzymatic activity; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Escherichia coli; Hepacivirus - enzymology; Hepatitis; Hepatitis C virus; Molecular Structure; Protein Binding; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; RNA polymerase; RNA Replicase - antagonists & inhibitors; RNA Replicase - genetics; RNA Replicase - metabolism; Viral Proteins - antagonists & inhibitors; Viral Proteins - genetics; Viral Proteins - metabolism
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1023/B:BIRY.0000040204.82885.f1

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.