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© Institut Pasteur
Corne d'Ammon (ou hippocampe) de renard atteint de rage sauvage. Coloration avec un conjugué fluorescent sur la nucléocapside du virus.
Publication : Bioorganic & medicinal chemistry

Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro.

Team: Lyssavirus epidemiology and neuropathology
Member: Wahiba Aouadi
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Bioorganic & medicinal chemistry - 31 Aug 2020

Thames JE, Waters CD, Valle C, Bassetto M, Aouadi W, Martin B, Selisko B, Falat A, Coutard B, Brancale A, Canard B, Decroly E, Seley-Radtke KL,

Link to Pubmed [PMID] – 33128910

Link to DOI – S0968-0896(20)30543-510.1016/j.bmc.2020.115713

Bioorg Med Chem 2020 Aug; 28(22): 115713

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 Yellow Fever Virus (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, and a secondary, albeit weak, effect on the DENV RNA-dependent RNA polymerase was observed at high concentrations. The results of these studies are reported herein.