Celgosivir: α-Glucosidase inhibitor anti-hepatitis C virus drug

Despite advances in antiviral therapeutics, hepatitis C virus (HCV) infection continues to be a major worldwide health concern. In the search for newer agents with novel mechanisms of action, such as compounds which target virus-specific enzymes, inhibition of α-glucosidase I is considered an attractive anti-HCV strategy since this enzyme is involved in the biosynthesis of glycoproteins that, when expressed on the viral surface, are essential for virus-host interactions. The naturally occurring iminosugar castanospermine is an α-glucosidase I inhibitor with marked antiviral activity against a number of viruses. Unfortunately, the agent also inhibits intestinal sucrases and causes osmotic diarrhea. In contrast, celgosivir, the 6-0-butanoyl derivative of castanospermine, is a relatively inactive inhibitor of intestinal sucrase and appears to be nontoxic to the gastrointestinal tract. It possesses antiviral activity that is 30-fold greater than the parent compound, its active metabolite. Celgosivir has displayed potent antiviral activity in vitro and in vivo against several viruses, including HIV-1, herpes simplex virus (HSV), bovine viral diarrhea virus (BVDV) and HCV, and the agent was chosen for further development as a treatment for HCV infection. The antiviral efficacy and safety of celgosivir were demonstrated in clinical trials in HIV-1-infected patients and it is currently undergoing phase II development for the treatment of HCV infection.