Journal article
A nuclear transport inhibitor that modulates the unfolded protein response and provides in vivo protection against lethal dengue virus infection
JE Fraser, S Watanabe, C Wang, WKK Chan, B Maher, A Lopez-Denman, C Hick, KM Wagstaff, JM Mackenzie, PM Sexton, SG Vasudevan, DA Jans
Journal of Infectious Diseases | Published : 2014
Abstract
Background. Dengue virus (DENV) is estimated to cause 390 million infections each year, but there is no licensed vaccine or therapeutic currently available. Methods. We describe a novel, high-throughput screen to identify compounds inhibiting the interaction between DENV nonstructural protein 5 and host nuclear transport proteins. We document the antiviral properties of a lead compound against all 4 serotypes of DENV, antibody-dependent enhanced (ADE) infection, and ex vivo and in vivo DENV infections. In addition, we use quantitative reverse-transcription polymerase chain reaction to examine cellular effects upon compound addition. Results. We identify N-(4-hydroxyphenyl) retinamide (4-HPR)..
View full abstractGrants
Awarded by National Health and Medical Research Council Australia
Awarded by Singapore National Medical Research Council
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council Australia (project grants 606409 and APP59137, senior principal research fellowship APP1002486, and principal research fellowship APP1059015); the Victorian Infection and Immunity Network Industry Alliance's Collaborative, State Government of Victoria's Collaborative Networks Pilot Program (project grant), the Duke-NUS Signature Research Program, Singapore Ministry of Health; and the Singapore National Medical Research Council (NMRC/1315/2011).