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The **Hepatitis C virus RNA replication complex** refers to a multi-protein assembly formed on rearranged host-cell endoplasmic reticulum membranes, sometimes called “membranous webs,” which is essential for amplification of the HCV RNA genome. This complex contains key non-structural proteins synthesized from a polyprotein precursor, primarily **NS3/4A protease**, **NS5A phosphoprotein**, **NS4B scaffolding protein**, and the **NS5B RNA-dependent RNA polymerase**. The main function of the complex is to catalyze the synthesis of complementary negative-strand RNA, which serves as a template for the production of new viral positive-strand genomes. Formation, activity, and regulation of the replication complex depend on both viral protein–protein and protein–RNA interactions, as well as on the recruitment of specific host-cell factors. The complex is the principal target of direct-acting antivirals (DAAs) that inhibit one or more of the essential enzymatic activities (protease, polymerase, or NS5A interactions), and it plays a central role in maintaining persistent HCV infection, which can result in chronic liver disease and cancer[1][2][5][6][7].
Inhibition of RNA-dependent RNA polymerase (NS5B)\nInhibition of NS5A replication complex assembly/function\nInhibition of viral NS3/4A protease required for polyprotein processing and replication complex maturation[2][6][7].
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