posted on 2014-05-22, 00:00authored byAlba Gigante, María-Dolores Canela, Leen Delang, Eva-María Priego, María-José Camarasa, Gilles Querat, Johan Neyts, Pieter Leyssen, María-Jesús Pérez-Pérez
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.