Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro
- Thames, Joy E.
- Waters, Charles D.
- Valle, Coralie
- Bassetto, Marcella
- Aouadi, Wahiba
- Martin, Baptiste
- Selisko, Barbara
- Falat, Arissa
- Coutard, Bruno
- Brancale, Andrea
- Canard, Bruno
- Decroly, Etienne
- Seley-Radtke, Katherine L.
DOIAbstract
Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues (“fleximers”) of the FDA-approved nucleoside Acyclovir that exhibit activity against various RNA viruses, demonstrating their broad-spectrum potential. The current study reports activity against DENV and YFV, particularly for compound 1. Studies to elucidate the mechanism of action suggest the flex-analogue triphosphates, especially 1-TP, inhibit DENV and ZIKV methyltransferases. The results of these studies are reported herein
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