Chemical Targeting of a G-Quadruplex RNA in the Ebola Virus L Gene.
Cell Chem Biol
; 23(9): 1113-1122, 2016 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-27617851
ABSTRACT
In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Porfirinas
/
RNA Viral
/
Ebolavirus
/
Quadruplex G
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China