New NS5B polymerase inhibitors for hepatitis C

IMPORTANCE OF THE FIELD: The current treatment of chronic hepatitis C based on the combination of pegylated interferon and ribavirin is effective in only 50% of patients. Specific targeted antiviral therapies represent a promising approach to eradicate the infection. AREAS COVERED IN THIS REVIEW: This review focuses on progress towards the development of the hepatitis C virus (HCV) polymerase inhibitors that have entered clinical development in recent years. WHAT THE READER WILL GAIN: Nucleos(t)ide analogues target the active site of the HCV polymerase and acts as chain terminators. They have similar activity against all genotypes and the virus has a high genetic barrier to drug resistance. Non-nucleoside inhibitors achieve polymerase inhibition by binding to one of the at least four allosteric enzyme sites. Most of them have a genotype-specific activity and they may select rapidly drug-resistant variants if HCV replication is not completely suppressed. Nonetheless, they provide additional options for addressing the needs of infected patients. TAKE HOME MESSAGE: NS5B polymerase inhibitors will form an integral part of more effective anti-HCV therapy, in combination with interferon or with other directly acting antiviral agents.