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Hepatitis C virus nonstructural protein 5A (NS5A) is a critical, multifunctional zinc-binding phosphoprotein lacking enzymatic activity, required for HCV genome replication, virion assembly, and modulation of host cell pathways. NS5A comprises three domains and is membrane-associated via an N-terminal amphipathic α-helix. NS5A interacts with both viral and host factors, regulates interferon responses, and its structural flexibility is essential for multiple infection stages. NS5A is a validated direct-acting antiviral target, with several highly potent NS5A inhibitors forming the backbone of modern HCV curative regimens.
Inhibitors bind domain I of NS5A, blocking RNA replication and virion assembly\nPrevent formation of replication complexes and membrane remodeling in infected hepatocytes\nMay alter phosphorylation status and subcellular localization of NS5A\nLead to rapid decline in HCV RNA levels by interfering with multiple stages of the viral life cycle
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