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 ORCID: https://orcid.org/0000-0002-2491-5868, Aouadi, Wahiba, Martin, Baptiste, Selisko, Barbara, Falat, Arissa, Coutard, Bruno, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Canard, Bruno, Decroly, Etienne and Seley-Radtke, Katherine L. 2020. Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro. Bioorganic and Medicinal Chemistry 28 (22) , 115713. 10.1016/j.bmc.2020.115713

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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 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy
Publisher:	Elsevier
ISSN:	0968-0896
Date of First Compliant Deposit:	8 September 2020
Date of Acceptance:	12 August 2020
Last Modified:	12 Nov 2024 21:15
URI:	https://orca.cardiff.ac.uk/id/eprint/134727

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