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

• Published in: Science advances Vol. 2; no. 4; p. 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: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.04.2016
• 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; guanine-rich consensus sequence; targeting G-quadruplex RNA
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.1501535

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.