Structure-Activity Relationships in the Development of Allosteric Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors: Ten Years of Research  
[Full paper ]
R. Haudecoeur, M. Peuchmaur, A. Ahmed-Belkacem, J.-M. Pawlotsky,A. Boumendjel
Med. Res. Rev. 2013, 33, 934-984.
A review. Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC)​. Hepatitis C virus (HCV) possesses a single pos. strand RNA genome encoding a polyprotein composed of approximatively 3000 amino acids. The polyprotein is cleaved at multiple sites by cellular and viral proteases to liberate structural and nonstructural (NS) proteins. NS5B, the RNA-​dependent RNA polymerase (RdRp)​, which catalyzes the HCV RNA replication has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-​acting antivirals)​. In the last 10 years, a growing no. of non-​nucleoside compds. have been reported as RdRp inhibitors and few are undergoing clin. trials. Over the past 5 years, several reviews were published all describing potentially active mols. To the best of our knowledge, only one review covers the structure-​activity relationships.1 In this review, we will discuss the reported non-​nucleoside mols. acting as RdRp inhibitors according to their chem. class esp. focusing on structure-​activity relationship aspects among each class of compds. Thereafter, we will attempt to address the global structural requirements needed for the design of specific inhibitors of RdRp.