Antiviral activities of sulfonium-ion glucosidase inhibitors and 5-thiomannosylamine disaccharide derivatives against dengue virus
Author(s)
Mohan, Sankar
McAtamney, Sarah
Jayakanthan, Kumarasamy
Eskandari, Razieh
von Itzstein, Mark
Pinto, B Mario
Year published
2012
Metadata
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Enzymes involved in N-glycan processing are targets of interest in the inhibition of host processes for the blockade of dengue virus (DENV) morphogenesis. Of the ten proteins encoded by DENV, three have N-glycosylation sites, namely pre-membrane/membrane protein (prM/M), envelope protein (E) and non-structural protein-1 (NS1). It is known that aberrations in the oligosaccharide portions at these N-glycan sites affect proper folding of these proteins during the translation process that, in turn, affects the morphogenesis of the budding DENV. Here we report on the testing for antiviral activity of four known sulfonium-ion ...
View more >Enzymes involved in N-glycan processing are targets of interest in the inhibition of host processes for the blockade of dengue virus (DENV) morphogenesis. Of the ten proteins encoded by DENV, three have N-glycosylation sites, namely pre-membrane/membrane protein (prM/M), envelope protein (E) and non-structural protein-1 (NS1). It is known that aberrations in the oligosaccharide portions at these N-glycan sites affect proper folding of these proteins during the translation process that, in turn, affects the morphogenesis of the budding DENV. Here we report on the testing for antiviral activity of four known sulfonium-ion a-glucosidase inhibitors and two 5-thiomannosylamine disaccharide derivatives against DENV. Two of the sulfonium ions tested, namely, kotalanol and its de-O-sulfonated derivative, naturally occurring potent intestinal a-glucosidase inhibitors, had comparable inhibitory activity [50% inhibitory concentration (IC50) = 25.1 ᠱ3.1 占and 50.4 ᠸ.6 卬 respectively] with that of ribavirin (IC50 = 25.2 ᠸ.3 卩, a commercially available antiviral agent. The 5-thiomannosylamines did not show any activity at the concentrations tested.
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View more >Enzymes involved in N-glycan processing are targets of interest in the inhibition of host processes for the blockade of dengue virus (DENV) morphogenesis. Of the ten proteins encoded by DENV, three have N-glycosylation sites, namely pre-membrane/membrane protein (prM/M), envelope protein (E) and non-structural protein-1 (NS1). It is known that aberrations in the oligosaccharide portions at these N-glycan sites affect proper folding of these proteins during the translation process that, in turn, affects the morphogenesis of the budding DENV. Here we report on the testing for antiviral activity of four known sulfonium-ion a-glucosidase inhibitors and two 5-thiomannosylamine disaccharide derivatives against DENV. Two of the sulfonium ions tested, namely, kotalanol and its de-O-sulfonated derivative, naturally occurring potent intestinal a-glucosidase inhibitors, had comparable inhibitory activity [50% inhibitory concentration (IC50) = 25.1 ᠱ3.1 占and 50.4 ᠸ.6 卬 respectively] with that of ribavirin (IC50 = 25.2 ᠸ.3 卩, a commercially available antiviral agent. The 5-thiomannosylamines did not show any activity at the concentrations tested.
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Journal Title
International Journal of Antimicrobial Agents
Volume
40
Issue
3
Subject
Virology
Medical microbiology
Pharmacology and pharmaceutical sciences
Microbiology