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

نویسندگان

  • Shao-Ru Wang
  • Yuan-Qin Min
  • Jia-Qi Wang
  • Chao-Xing Liu
  • Bo-Shi Fu
  • Fan Wu
  • Ling-Yu Wu
  • Zhi-Xian Qiao
  • Yan-Yan Song
  • Guo-Hua Xu
  • Zhi-Guo Wu
  • Gai Huang
  • Nan-Fang Peng
  • Rong Huang
  • Wu-Xiang Mao
  • Shuang Peng
  • Yu-Qi Chen
  • Ying Zhu
  • Tian Tian
  • Xiao-Lian Zhang
  • Xiang Zhou
چکیده

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.

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عنوان ژورنال:
  • Science advances

دوره 2 4  شماره 

صفحات  -

تاریخ انتشار 2016