Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing.
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).
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
D017485:1-Deoxynojirimycin; D000470:Alkaloids; D000998:Antiviral Agents; D005944:Glucosamine; D006023:Glycoproteins; D006026:Glycoside Hydrolases; D007212:Indolizines; C037806:castanospermine; D054836:Indolizidines