New NS5B polymerase inhibitors for hepatitis C.
BACKGROUND
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.


METHODS
This review focuses on progress towards the development of the hepatitis C virus (HCV) polymerase inhibitors that have entered clinical development in recent years.


RESULTS
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.


CONCLUSIONS
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.
Legrand-Abravanel
Florence
F
CHU Toulouse, Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, France. abravanel.f@chu-toulouse.fr
Nicot
Florence
F
Izopet
Jacques
J
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015507:Drugs, Investigational; D004791:Enzyme Inhibitors; D009705:Nucleosides; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase