title: Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing.
abstract: The objective of this study was to investigate the antiretroviral activity of specific inhibitors of glycosidases and mannosidases that are involved in N-linked oligosaccharide processing of glycoproteins. Castanospermine and 1-deoxynojirimycin, potent inhibitors of glucosidases I and II, showed significant activity against Moloney murine leukemia virus (IC50: 1.2 microgram/ml). Deoxymannojirimycin and swainsonine, inhibitors of mannosidase I and II, respectively, did not show any activity. These observations suggest that removal of the outermost glucose residue from high mannose asparagine-linked oligosaccharide may be essential for the replication of mouse leukemia virus. The relative nontoxic nature of these inhibitors and a novel mechanism of action suggest a potential for compounds of this type as chemopreventive and therapeutic agents in the treatment of acquired immune deficiency syndrome (AIDS).
mesh_terms: D017485:1-Deoxynojirimycin; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D007212:Indolizines; D051379:Mice; D008979:Moloney murine leukemia virus / Q000187:drug effects / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D054836:Indolizidines
chemical_list: D017485:1-Deoxynojirimycin; D000470:Alkaloids; D000998:Antiviral Agents; D005944:Glucosamine; D006023:Glycoproteins; D006026:Glycoside Hydrolases; D007212:Indolizines; C037806:castanospermine; D054836:Indolizidines