Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro.
Bioorg Med Chem
; 28(22): 115713, 2020 11 15.
Article
em En
| MEDLINE
| ID: mdl-33128910
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Flavivirus
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Nucleosídeos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article