title: RNA aptamer-mediated interference of HCV replication by targeting the CRE-5BSL3.2 domain.
abstract: The RNA genome of hepatitis C virus (HCV) contains multiple conserved structural RNA domains that play key roles in essential viral processes. A conserved structural component within the 3' end of the region coding for viral RNA-dependent RNA polymerase (NS5B) has been characterized as a functional cis-acting replication element (CRE). This study reports the ability of two RNA aptamers, P-58 and P-78, to interfere with HCV replication by targeting the essential 5BSL3.2 domain within this CRE. Structure-probing assays showed the binding of the aptamers to the CRE results in a structural reorganization of the apical portion of the 5BSL3.2 stem-loop domain. This interfered with the binding of the NS5B protein to the CRE and induced a significant reduction in HCV replication (≈50%) in an autonomous subgenomic HCV replication system. These results highlight the potential of this CRE as a target for the development of anti-HCV therapies and underscore the potential of antiviral agents based on RNA aptamer molecules.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Marton
authors.forename: C
authors.initials: C
authors.lastname: Romero-López
authors.forename: A
authors.initials: A
authors.lastname: Berzal-Herranz
mesh_terms: D052157:Aptamers, Nucleotide / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D016384:Consensus Sequence; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D055029:Inverted Repeat Sequences; D008969:Molecular Sequence Data; D038621:Regulatory Sequences, Ribonucleic Acid; D052156:SELEX Aptamer Technique; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D052157:Aptamers, Nucleotide; D038621:Regulatory Sequences, Ribonucleic Acid; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase