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Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS.
J Virol. 2005 Jul;79(14):8698-706
Castanospermine, a potent inhibitor of dengue virus infection in vitro and
in vivo.
Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS.
Department of Medicine, Washington University School of Medicine, 660 South
Euclid Avenue, Box 8051, St. Louis, MO 63110, USA.
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
PMID: 15994763
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