title: An iminosugar with potent inhibition of dengue virus infection in vivo.
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.
authors: La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors: Stuart T
authors: ST
authors: Perry
authors: Michael D
authors: MD
authors: Buck
authors: Emily M
authors: EM
authors: Plummer
authors: Raju A
authors: RA
authors: Penmasta
authors: Hitesh
authors: H
authors: Batra
authors: Eric J
authors: EJ
authors: Stavale
authors: Kelly L
authors: KL
authors: Warfield
authors: Raymond A
authors: RA
authors: Dwek
authors: Terry D
authors: TD
authors: Butters
authors: Dominic S
authors: DS
authors: Alonzi
authors: Steven M
authors: SM
authors: Lada
authors: Kevin
authors: K
authors: King
authors: Brennan
authors: B
authors: Klose
authors: Urban
authors: U
authors: Ramstedt
authors: Sujan
authors: S
authors: Shresta
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines; D003715:Dengue / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D050111:Imino Sugars