Previous studies have suggested that
alpha-glucosidase inhibitors such as
castanospermine and deoxynojirimycin inhibit dengue virus type 1
infection by disrupting the folding of the structural
proteins prM and E, a step crucial to viral secretion. We extend these studies by evaluating the inhibitory activity of
castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and West Nile virus. Using in vitro assays we demonstrated that
infections by all serotypes of dengue virus were inhibited by
castanospermine. In contrast, yellow fever virus and West Nile virus were partially and almost completely resistant to the effects of the
drug, respectively.
Castanospermine inhibited dengue virus
infection at the level of secretion and infectivity of viral particles. Importantly,
castanospermine prevented mortality in a mouse model of dengue virus
infection, with doses of 10, 50, and 250 mg/kg of
body weight per day being highly effective at promoting survival (P < or = 0.0001). Correspondingly,
castanospermine had no adverse or protective effect on West Nile virus mortality in an analogous mouse model. Overall, our data suggest that
castanospermine has a strong
antiviral effect on dengue virus
infection and warrants further development as a possible treatment in humans.