Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro.
Basic Information
ID: ALA4699605
Journal: Bioorg Med Chem
Title: Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro.
Authors: 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
Abstract: 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.
CiteXplore: 33128910
DOI: 10.1016/j.bmc.2020.115713
Patent ID: ┄