Hepatitis C virus NS3-4A protease inhibitors: countering viral subversion in vitro and showing promise in the clinic.
Hepatitis C virus (HCV) NS3.4A protease inhibitors have potential for treating chronic HCV disease. Robust antiviral effects have been reported for the three HCV NS3.4A inhibitors (BILN-2061 (ciluprevir), telaprevir (VX-950; Vertex Pharmaceuticals Inc./Janssen Pharnmaceutica NV/Mitsubishi Pharma Corp.) and SCH-503034; Schering-Plough Research Institute) that have been studied in clinical trials to date in HCV-infected patients, and new inhibitor molecules continue to appear on the horizon. Herein, toe relate the remarkable progress of these drug candidates to recent evidence that suggests HCV might depend on NS3.4A protease to subvert multiple innate cellular defense mechanisms.
Thomson
John A
JA
Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA.
Perni
Robert B
RB
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016174:Hepacivirus / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases