Alpha-glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum.
We report that endoplasmic reticulum alpha-glucosidase inhibitors have antiviral effects on dengue (DEN) virus. We found that glucosidase inhibition strongly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (envelope protein): the proper folding of prM bearing unprocessed N-linked oligosaccharide is inefficient, and this causes delayed formation of prME heterodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of alpha-glucosidase-mediated N-linked oligosaccharide trimming may thus prevent the assembly of DEN virus by affecting the early stages of envelope glycoprotein processing.
Courageot
M P
MP
Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, 75724 Paris, France.
Frenkiel
M P
MP
Dos Santos
C D
CD
Deubel
V
V
Desprès
P
P
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000821:virology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D015678:Viral Structural Proteins / Q000737:chemistry / Q000378:metabolism; D014771:Virion / Q000254:growth & development*; D014779:Virus Replication / Q000187:drug effects*; D000520:alpha-Glucosidases / Q000494:pharmacology*; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D004791:Enzyme Inhibitors; D007212:Indolizines; D015678:Viral Structural Proteins; D000520:alpha-Glucosidases; C037806:castanospermine; D054836:Indolizidines