An iminosugar with potent inhibition of dengue virus infection in vivo.

Authors :: Perry ST
Buck MD
Plummer EM
Penmasta RA
Batra H
Stavale EJ
Warfield KL
Dwek RA
Butters TD
Alonzi DS
Lada SM
King K
Klose B
Ramstedt U
Shresta S
Source :: Antiviral research [Antiviral Res] 2013 Apr; Vol. 98 (1), pp. 35-43. Date of Electronic Publication: 2013 Jan 31.
Publication Year :: 2013
Abstract: The aim of the present study was to evaluate the ability of the iminosugar drug UV-4 to provide in vivo protection from lethal dengue virus (DENV) challenge. This study utilized a well-described model of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)-like lethal disease in AG129 mice lacking the type I and II interferon receptors. Herein, we present UV-4 as a potent iminosugar for controlling DENV infection and disease in this mouse model. Specifically, administration of UV-4 reduced mortality, as well as viremia and viral RNA in key tissues, and cytokine storm. In addition, UV-4 treatment can be delayed, and it does not alter the anti-DENV antibody response. These results have set the foundation for development of UV-4 as a DENV-specific antiviral in phase I human clinical trials.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)