Antiviral activities of sulfonium-ion glucosidase inhibitors and 5-thiomannosylamine disaccharide derivatives against dengue virus.
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 α-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 α-glucosidase inhibitors, had comparable inhibitory activity [50% inhibitory concentration (IC(50))=25.1±13.1 μM and 50.4±8.6 μM, respectively] with that of ribavirin (IC(50)=25.2±8.3 μM), a commercially available antiviral agent. The 5-thiomannosylamines did not show any activity at the concentrations tested.
Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Sankar
S
Mohan
Sarah
S
McAtamney
Kumarasamy
K
Jayakanthan
Razieh
R
Eskandari
Mark
M
von Itzstein
B Mario
BM
Pinto
D000606:Amino Sugars / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000187:drug effects*; D004187:Disaccharides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D013452:Sulfonium Compounds / Q000494:pharmacology*; D014709:Vero Cells
D000606:Amino Sugars; D000998:Antiviral Agents; D004187:Disaccharides; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013452:Sulfonium Compounds; C010215:mannosylamine