title: A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target.
abstract: 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.
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Shao-Ru
authors.identifier: 0000-0002-9609-849X
authors.initials: SR
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, School of Medicine, Wuhan University, Wuhan 430071, Hubei, China.
authors.forename: Yuan-Qin
authors.identifier: 0000-0002-1528-3969
authors.initials: YQ
authors.lastname: Min
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Jia-Qi
authors.identifier: 0000-0002-4015-3437
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Chao-Xing
authors.initials: CX
authors.lastname: Liu
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Bo-Shi
authors.identifier: 0000-0002-5695-0991
authors.initials: BS
authors.lastname: Fu
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Fan
authors.identifier: 0000-0001-7036-7674
authors.initials: F
authors.lastname: Wu
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Ling-Yu
authors.identifier: 0000-0001-8491-4683
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, China.
authors.forename: Zhi-Xian
authors.identifier: 0000-0002-0154-2317
authors.initials: ZX
authors.lastname: Qiao
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Song
authors.affiliation: Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, Hubei, China.
authors.forename: Guo-Hua
authors.identifier: 0000-0001-5087-6818
authors.initials: GH
authors.lastname: Xu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Gai
authors.initials: G
authors.lastname: Huang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Nan-Fang
authors.initials: NF
authors.lastname: Peng
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Wu-Xiang
authors.initials: WX
authors.lastname: Mao
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Shuang
authors.identifier: 0000-0002-2265-0480
authors.initials: S
authors.lastname: Peng
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Yu-Qi
authors.identifier: 0000-0002-5635-3409
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Tian
authors.identifier: 0000-0002-0340-230X
authors.initials: T
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, School of Medicine, Wuhan University, Wuhan 430071, Hubei, China.
authors.forename: Xiao-Lian
authors.identifier: 0000-0002-8283-9381
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan 430072, Hubei, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
mesh_terms: D017124:Conserved Sequence; D054856:G-Quadruplexes; D015316:Genetic Therapy; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology; D014758:Viral Core Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics
chemical_list: D012367:RNA, Viral; D054852:Small Molecule Libraries; D014758:Viral Core Proteins
keywords: guanine-rich consensus sequence; targeting G-quadruplex RNA