The therapeutic potential of NS3 protease inhibitors in HCV infection.
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide and afflicts > 170 million people. The HCV-encoded NS3 protease is essential for viral replication and has long been recognised as a prime target for antiviral drugs. However, the peculiar active site structure of this enzyme, a shallow dent on the surface of the protein, has rendered the development of small-molecule inhibitors a highly challenging task. Nevertheless, perseverance and creativity has led to significant progress in this field over the last few years resulting in three compounds that are reported to enter the clinic. The impressive reduction of HCV RNA plasma levels observed with two of these inhibitors (ciluprevir and VX-950) in clinical trials has undoubtedly illustrated the potential of this viral enzyme-targeted drug discovery approach.
Goudreau
Nathalie
N
Department of Chemistry, Research & Development, Boehringer Ingelheim Ltd, 2100 Cunard Street, Laval, Québec, H7S 2G5, Canada. ngoudreau@lav.boehringer-ingelheim.com
Llinàs-Brunet
Montse
M
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D015842:Serine Proteinase 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