Journal
JOURNAL OF VIROLOGY
Volume 90, Issue 21, Pages 9683-9692Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01347-16
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Funding
- Laboratoire d'Excellence via Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- Equipe FRM from the French Fondation pour la Recherche Medicale [DEQ20150331759]
- Institut Pasteur Defeat Dengue Program
- Erasmus+ Unipharma-Graduates Program
- Amgen Scholars Program at Institut Pasteur
- Het Weerstandfonds
- NIH [R01AI108197, U19 AI109680]
- Institut Pasteur Programme Transversal de Recherche [ZPTR484]
- Fondation Total [S-CM15010-05B]
- Roux Howard Cantarini postdoctoral fellowship
- Seventh Framework Programme [278433-PREDEMICS]
- Ministry of Defense, Direction Generale de l'Armement
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RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise in vitro and in vivo, these outbreaks underscore the need to accelerate drug discovery. The replication of several viruses has been described to rely on host polyamines, small and abundant positively charged molecules found in the cell. Here, we describe the antiviral effects of two molecules that alter polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhibitor of ornithine decarboxylase 1 (ODC1), and diethylnorspermine (DENSpm), an activator of spermidine/spermine N-1-acetyltransferase (SAT1). We show that reducing polyamine levels has a negative effect on diverse RNA viruses, including several viruses involved in recent outbreaks, in vitro and in vivo. These findings highlight the importance of the polyamine biosynthetic pathway to viral replication, as well as its potential as a target in the development of further antivirals or currently available molecules, such as DFMO.
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