Recent developments in the discovery of hepatitis C virus serine protease inhibitors--towards a new class of antiviral agents?
Hepatitis C virus (HCV) infection is an epidemic disease and a significant worldwide health problem. Despite impressive improvements in the efficacy of the standard, interferon-based therapies, at present, the virus can not be eradicated in the majority of infected individuals. The last decade has witnessed a burst in our understanding of the molecular biology of HCV infection and lead to the identification of essential features of the viral genome that are being targeted for the development of specific antiviral agents. The non-structural protein 3 of the HCV genome harbours a serine protease domain that is essential for viral replication. This enzyme has been studied in great detail and the wealth of structural and functional data are presently nurturing drug development efforts. The peculiar active site structure of the enzyme imposes considerable obstacles to the development of small molecule inhibitors. However, the combination of creativity with the powerful tools of modern drug discovery has led to impressive progress in this field over the past few years and, as a result, the first compounds are now entering clinical trials.
Narjes
Frank
F
Instituto di Ricerche di Biologia Molecolare-Merck Research Laboratories Rome,Via Pontina Km 30,600,00040 Pomezia, Italy.
Koch
Uwe
U
Steinkühler
Christian
C
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; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases