title: Identification of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as novel inhibitors of Chikungunya virus replication.
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.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, Madrid E-28006, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Gigante
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Canela
authors.forename: Leen
authors.initials: L
authors.lastname: Delang
authors.forename: Eva-María
authors.initials: EM
authors.lastname: Priego
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
authors.forename: Gilles
authors.initials: G
authors.lastname: Querat
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Pérez-Pérez
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D002522:Chlorocebus aethiops; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011744:Pyrimidinones; D014230:Triazoles