The alpha(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin potentiates the antiviral activity of carbohydrate-binding agents against wild-type and mutant HIV-1 strains containing glycan deletions in gp120.
Exposure of carbohydrate-binding agents (CBAs) (i.e. the mannose-specific plant lectins Hippeastrum hybrid agglutinin and Galanthus nivalis agglutinin) to HIV-1 progressively select for mutant HIV-1 strains that contain N-glycan deletions in their envelope gp120. This results in resistance of the mutant virus strains to the CBAs. Exposure of such mutant virus strains to the alpha(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin (DMJ) results in an enhanced suppression of mutant virus-induced cytopathicity in CEM cell cultures. Moreover, when combined with CBAs at concentrations that showed poor if any suppression of mutant virus replication as single drugs, a synergistic antiviral activity of DMJ was observed. These observations argue for a combined exposure of CBAs and glycosylation inhibitors such as DMJ to HIV to afford a more pronounced suppression of virus replication, prior to, or during, CBA resistance development.
Balzarini
Jan
J
Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. jan.balzarini@rega.kuleuven.be
D017485:1-Deoxynojirimycin / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D006031:Glycosylation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects*; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D009154:Mutation / Q000235:genetics*; D011134:Polysaccharides / Q000378:metabolism
D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D006388:Hemagglutinins; D011134:Polysaccharides; D017485:1-Deoxynojirimycin; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase