Researchers have discovered guanine-rich RNA sequences known as G quadruplex structures in the core gene of the hepatitis C virus. These foldable amino acid structures have previously been associated with HIV, herpes simplex virus, and epstein-barr virus, and may be involved in viruses’ replication cycles – making them promising targets for therapy. However, the role of G quadruplex structures in controlling gene expression remains poorly understood. Hepatitis C virus infection is estimated to affect 2.8% of the population worldwide, and due to the ability of the virus to rapidly mutate and develop resistance to drugs, there is an urgent need for better treatments with lower costs.
It’s been proposed that developing compounds that target highly conserved regions or structural motifs in the hepatitis C virus genome could potentially protect against not only the current virus, but future mutated versions. Using bioinformatics techniques, Xiang Zhou et al. discovered a highly conserved sequence of guanine residues in the hepatitis C virus genome, along with evidence suggesting that the sequence folds into a G quadruplex structure. The authors also show that small molecules specifically designed to stabilize the G-quadruplex structure can reduce RNA replication and block protein translation of intracellular hepatitis C (an essential step for viral replication). The results imply that stabilizing G-quadruplex RNA in the genome of hepatitis C could be a new strategy for anti-viral drug development.
Article: A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target, S.-R. Wang; Y.-Q. Min; J.-Q. Wang; C.-X. Liu; B.-S. Fu; F. Wu; L.-Y. Wu; Y.-Y. Song; Z.-G. Wu; G. Huang; N.-F. Peng; R. Huang; W.-X. Mao; S. Peng; Y.-Q. Chen; Y. Zhu; T. Tian; X.-L. Zhang; X. Zhou, Z.-X. Qiao; G.-H. Xu; X. Zhou, Science Advances, doi: 10.1126/sciadv.1501535, published 1 April 2016.