Author: 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.
Title: Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro Cord-id: q4qdn0mo Document date: 2020_8_31
ID: q4qdn0mo
Snippet: 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 (“fleximersâ€) 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 e
Document: 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 (“fleximersâ€) 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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