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

• Published in: Biochemistry (Moscow) Vol. 71; no. 9; pp. 1021 - 1026
• Main Authors: Kozlov, M V, Polyakov, K M, Ivanov, A V, Filippova, S E, Kuzyakin, A O, Tunitskaya, V L, Kochetkov, S N
• Format: Journal Article
• Language: English
• Published: United States Springer 01-09-2006; Springer Nature B.V
• Subjects: Aminobutyrates - pharmacology; Binding Sites; Biochemistry; Catalysis; Cations; Chelating Agents - pharmacology; Chelation; Enzymes; Genetic aspects; Hepacivirus - enzymology; Hepatitis; Hepatitis C virus; Magnesium; Magnesium - chemistry; Models, Molecular; Molecules; Phenylbutyrates; Pyrogallol - analogs & derivatives; Pyrogallol - pharmacology; Reverse transcriptase; RNA polymerase; RNA Replicase - antagonists & inhibitors
• ISSN: 0006-2979; 1608-3040; 0320-9725
• DOI: 10.1134/S0006297906090112

Pyrogallol reversibly and noncompetitively inhibits the activity of the hepatitis C RNA-dependent RNA polymerase. 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.