Title: Identification of [1,2,3]Triazolo[4,5-d]pyrimidin-7(6H)-ones as Novel Inhibitors of Chikungunya Virus Replication
Authors: Gigante, Alba ×
Canela, María-Dolores
Delang, Leen
Priego, Eva-María
Camarasa, María-José
Querat, Gilles
Neyts, Johan
Leyssen, Pieter
Pérez-Pérez, María-Jesús #
Issue Date: May-2014
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:57 issue:10 pages:4000-8
Article number: 10.1021/jm401844c
Abstract: Chikungunya virus (CHIKV) is a re-emerging Alphavirus that is transmitted to humans by Aedes mosquitoes. Currently, there are still no drugs or vaccines available for the treatment or prevention of this disease. Although traditionally restricted to Africa and Asia, the adaptation of the virus to Aedes albopictus, a mosquito species with an almost worldwide distribution, has contributed to the geographical spread of this virus in the past decade. Here, we report on a new family of compounds named [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones that inhibit CHIKV replication in the low micromolar range with no toxicity to the host (Vero) cells. The most potent compound in this series has an EC50 value below 1 μM with no cytotoxicity detected up to 668 μM, therefore affording a selectivity index greater than 600. Interestingly, the compounds have little or no antiviral activity on the replication of other members of the Togaviridae family. The exploration and study of this class of selective inhibitors of CHIKV replication will contribute to deeper insights into the CHIKV life cycle and may be a first step toward the development of a clinical drug candidate.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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