The α(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 α(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.