Chemical Targeting of a G-Quadruplex RNA in the Ebola Virus L Gene.
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.
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China.
Shao-Ru
SR
Wang
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Qiu-Yan
QY
Zhang
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China.
Jia-Qi
JQ
Wang
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Xing-Yi
XY
Ge
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China.
Yan-Yan
YY
Song
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China.
Ya-Fen
YF
Wang
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Xiao-Dan
XD
Li
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China.
Bo-Shi
BS
Fu
Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Guo-Hua
GH
Xu
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Bo
B
Shu
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China.
Peng
P
Gong
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province 430071, China. Electronic address: zhangbo@wh.iov.cn.
Bo
B
Zhang
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China. Electronic address: ttian@whu.edu.cn.
Tian
T
Tian
College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei Province 430072, China. Electronic address: xzhou@whu.edu.cn.
Xiang
X
Zhou
D029043:Ebolavirus / Q000187:drug effects* / Q000235:genetics*; D054856:G-Quadruplexes / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D011166:Porphyrins / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D011166:Porphyrins; D012367:RNA, Viral; C021096:tetra(4-N-methylpyridyl)porphine