2024-03-29T09:59:00Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1621192020-12-10T16:52:14Zcom_10261_81com_10261_5col_10261_334
DIGITAL.CSIC
author
Gigante, Alba
author
Gómez-SanJuan, Asier
author
Delang, Leen
author
Li, C.
author
Bueno, Oskía
author
Gamo, Ana María
author
Priego, Eva María
author
Camarasa Rius, María José
author
Jochmans, D.
author
Leyssen, Pieter
author
Decroly, E.
author
Coutard, Bruno
author
Querat, Guilles
author
Neyts, Johan
author
Peréz-Pérez, María-Jesús
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
European Commission
2018-03-13T10:54:12Z
2018-03-13T10:54:12Z
2017
Antiviral Research 144: 216-222 (2017)
http://hdl.handle.net/10261/162119
10.1016/j.antiviral.2017.06.003
http://dx.doi.org/10.13039/501100000780http://dx.doi.org/10.13039/501100010198
Chikungunya virus (CHIKV) is a re-emerging alphavirus transmitted to humans by Aedes mosquitoes. Since 2005, CHIKV has been spreading worldwide resulting in epidemics in Africa, the Indian Ocean islands, Asia and more recently in the Americas. CHIKV is thus considered as a global health concern. There is no specific vaccine or drug available for the treatment of this incapacitating viral infection. We previously identified 3-aryl-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as selective inhibitors of CHIKV replication and proposed the viral capping enzyme nsP1 as a target. This work describes the synthesis of novel series of related compounds carrying at the aryl moiety a methylketone and related oximes combined with an ethyl or an ethyl-mimic at 5-position of the triazolopyrimidinone. These compounds have shown antiviral activity against different CHIKV isolates in the very low μM range based on both virus yield reduction and virus-induced cell-killing inhibition assays. Moreover, these antivirals inhibit the in vitro guanylylation of alphavirus nsP1, as determined by Western blot using an anti-cap antibody. Thus, the data obtained seem to indicate that the anti-CHIKV activity might be related to the inhibition of this crucial step in the viral RNA capping machinery.
eng
closedAccess
Oximes
Chikungunya virus
Alphavirus
mRNA capping
Triazolopyrimidines
Antiviral activity of [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones against chikungunya virus targeting the viral capping nsP1
artículo
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
URL
https://digital.csic.es/bitstream/10261/162119/1/accesoRestringido.pdf
File
MD5
42637ae8545636bc41605c1740a9a84e
15753
application/pdf
accesoRestringido.pdf