Serine protease inhibitors as anti-hepatitis C virus agents.
Approximately 3% of the worldwide population (i.e., more than 170 million people) are chronically infected with the hepatitis C virus (HCV). An estimated 20% of these patients will develop liver cirrhosis within a mean of 20 years, and 2-5% of cirrhotic patients will die of end-stage liver disease or hepatocellular carcinoma. The currently approved antiviral therapy with pegylated interferon (pegIFN) and ribavirin induces a sustained virological response (SVR) in 40-50% of patients infected with genotype 1, the most prevalent HCV type. In this review, we focus on the development and clinical application of serine protease inhibitors as anti-HCV agents. Although highly active in inducing a significant decline of serum HCV RNA, the rapid development of resistance must be counteracted in combination with other antiviral agents, currently pegIFN-alpha and ribavirin. Two serine protease inhibitors have reached clinical Phase III trials, increasing SVR rates and shortening treatment duration when combined with pegIFN and ribavirin. Trials of interferon-free targeted combination therapies are currently underway.
Reiser
Markus
M
Department of Medicine & Gastroenterology, Klinikum Vest GmbH--Paracelsus-Klinik Marl, Lipper Weg 11, Marl, Germany. m.reiser@paracelsus-klinik-marl.de
Timm
Jörg
J
D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*
D000998:Antiviral Agents; D007370:Interferon Type I; D012367:RNA, Viral; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D012254:Ribavirin