Iminosugars as possible broad spectrum anti hepatitis virus agents: the glucovirs and alkovirs.
Glucosidases in the endoplasmic reticulum (ER) mediate the first step in processing N-linked oligosaccharides. Recent evidence suggests that morphogenesis and secretion of members of the hepatitis B and flavivirus families are more dependent on these enzymes than are most host glycoproteins. Thus, it is possible that glucosidase inhibitors can be designed that are safe and selective for the treatment of hepatitis B and possibly C (since hepatitis C virus is a member of the flavivirus family), making them broad spectrum with respect to hepatitis viruses. Numerous pharmacological and genetic dissections support the notion that glucosidase inhibition can have an antiviral effect, and imino sugars that competitively inhibit ER glucosidases have been proposed as anti-hepatitis drug candidates. We call this family of compounds 'glucovirs'. Recently, however, alkylated imino sugars that retain substantial antiviral activity but lack glucosidase inhibitory activity have been described. These compounds are called 'alkovirs' and their mechanism of action is unknown. This review considers the rationale of the glucovir and alkovir approach to the treatment of hepatitis B and C.
Block
T M
TM
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Doylestown, PA, USA. Tim.Block@mail.tju.edu
Jordan
R
R
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D014764:Viral Proteins / Q000378:metabolism
D000998:Antiviral Agents; D002241:Carbohydrates; D004791:Enzyme Inhibitors; D014764:Viral Proteins; D005959:Glucosidases