title: Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection.
abstract: Celgosivir, in development by MIGENIX Inc for the treatment of HCV infection, is an oral prodrug of the natural product castanospermine that inhibits alpha-glucosidase I, an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked oligosaccharides of viral envelope glycoproteins. Celgosivir is well absorbed in vitro and in vivo, and is rapidly converted to castanospermine. Celgosivir has a novel mechanism of action (ie, host-directed glycosylation), and demonstrates broad antiviral activity in vitro. The agent is not efficient as a monotherapy for the treatment of HCV, but has demonstrated a synergistic effect in combination with the current standard of care, PEGylated IFNalpha2b plus ribavirin, both in vitro and in phase II clinical trials. At the time of publication, a phase II trial was underway to investigate the safety, tolerability and antiviral effect of celgosivir in combination with PEGylated IFNalpha2b plus ribavirin for up to 1 year in patients with chronic HCV infection. Celgosivir may prove to be a valuable component for combination therapy and may help to prevent the apparition of drug resistance. Long-term toxicity studies are necessary to confirm the safety of this novel drug in humans.
authors: INSERM U871, Molecular Physiopathology and New Treatment of Viral Hepatitis, 151 cours Albert Thomas, Cedex 03 Lyon, France. david.durantel@inserm.fr
authors: David
authors: D
authors: Durantel
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D065089:Glycoside Hydrolase Inhibitors; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007212:Indolizines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D000520:alpha-Glucosidases; D054836:Indolizidines
chemical_list: D000998:Antiviral Agents; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011355:Prodrugs; D011994:Recombinant Proteins; D012254:Ribavirin; D000520:alpha-Glucosidases; C070715:celgosivir; D054836:Indolizidines; C042059:glucosidase I; C417083:peginterferon alfa-2b