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The Hepatitis C virus genome RNA is a single-stranded, positive-sense RNA molecule of ~9,650 nucleotides that encodes the entire viral proteome and is essential for all stages of the virus lifecycle, including replication, translation, and immune escape[2][5][3][6]. The genome is highly structured, containing elaborate secondary and tertiary RNA motifs distributed throughout untranslated regions (UTRs) and coding domains; these regulate critical functions such as polyprotein synthesis via an internal ribosome entry site (IRES) at the 5′ UTR, replication control elements (CREs) in the coding region, and specialized domains in the 3′ UTR for genome stability and packaging[1][4][6]. The HCV genomic RNA also interacts directly with host factors such as microRNA-122, enhancing viral replication and contributing to hepatotropism[2][4]. While not a classical drug target like a receptor or enzyme, the genome itself and its RNA elements are emerging as therapeutic targets due to their central role in the viral lifecycle and the success of drugs that indirectly inhibit HCV replication by targeting polymerase or protein-processing enzymes encoded by the genome[5][3]. Complex RNA folding and high sequence variability pose significant challenges for direct RNA-targeted therapies and monitoring, but quantitative detection of HCV RNA in blood remains the gold standard for diagnosis and monitoring of infection and response to treatment[5][2][4].
Inhibition of RNA-dependent RNA polymerase (NS5B); Blockage of viral RNA replication; Interference with polyprotein processing; Inhibition of RNA structure recognition
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