A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target

G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatiti...

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Bibliographic Details
Published in:Science advances 2016-04, Vol.2 (4), p.e1501535-e1501535
Main Authors: Wang, Shao-Ru, Min, Yuan-Qin, Wang, Jia-Qi, Liu, Chao-Xing, Fu, Bo-Shi, Wu, Fan, Wu, Ling-Yu, Qiao, Zhi-Xian, Song, Yan-Yan, Xu, Guo-Hua, Wu, Zhi-Guo, Huang, Gai, Peng, Nan-Fang, Huang, Rong, Mao, Wu-Xiang, Peng, Shuang, Chen, Yu-Qi, Zhu, Ying, Tian, Tian, Zhang, Xiao-Lian, Zhou, Xiang
Format: Article
Language:English
Subjects:
Chemical Biology
Conserved Sequence
G-Quadruplexes
Genetic Therapy
Genome, Viral
Hepacivirus - drug effects
Hepatitis C - drug therapy
Hepatitis C - virology
Humans
Nucleic Acid Conformation
RNA, Viral - drug effects
SciAdv r-articles
Small Molecule Libraries - pharmacology
Viral Core Proteins - antagonists & inhibitors
Viral Core Proteins - chemistry
Viral Core Proteins - genetics
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Summary:G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti-hepatitis C drug development.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.1501535