Interference of hepatitis C virus replication in cell culture by antisense peptide nucleic acids targeting the X-RNA.

摘要: The RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is the essential catalytic enzyme for viral genome replication. It initiates minus-strand synthesis from a highly conserved 98-nt sequence, called X-RNA, at 3'-end plus-strand genome. In this study, we evaluated antiviral effects peptide nucleic acids (PNAs) targeting X-RNA. Our in vitro RdRp assay results showed that PNAs three major stem-loop (SL) domains X-RNA can inhibit initiation. Delivery X-RNA-targeted by fusing to cell-penetrating peptides (CPPs) into HCV-replicating cells effectively suppressed HCV Electrophoretic mobility shift assays revealed PNA SL3 region 5'-end dissociated Furthermore, delivery SL3-targeted HCV-infected resulted suppression replication without activation interferon β expression. Collectively, our indicate be targeted CPP-fused block RNA-protein and/or RNA-RNA interactions and identify as an binding site crucial addition, ability initiation using antisense suggests their promising therapeutic potential against infection.