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, 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:	Pharmacy
Publisher:	Elsevier
ISSN:	0968-0896
Date of First Compliant Deposit:	8 September 2020
Date of Acceptance:	12 August 2020
Last Modified:	06 Jan 2024 08:28
URI:	https://orca.cardiff.ac.uk/id/eprint/134727

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