alpha-glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum

We report that endoplasmic reticulum or-glucosidase inhibitors have antivir al effects on dengue (DEN) virus. We found that glucosidase inhibition stro ngly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (e nvelope protein): the proper folding of prM bearing unprocessed N-linked ol igosaccharide is inefficient, and this causes delayed formation of prME het erodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of or-gluco sidase-mediated N-linked oligosaccharide trimming may thus prevent the asse mbly of DEN virus by affecting the early stages of envelope glycoprotein pr ocessing.