Non-structural protein 5A (NS5A)

Non-structural protein 5A (NS5A) is a multifunctional, zinc-binding, proline-rich hydrophilic phosphoprotein that plays a central role in the life cycle of the Hepatitis C virus (HCV), particularly in viral RNA replication and assembly. It interacts with other viral and host cellular proteins, exists predominantly as a dimer, and associates with intracellular membranes via an N-terminal amphipathic α-helix. NS5A comprises three domains, with domains II & III being largely natively unfolded, allowing conformational flexibility for diverse interactions. NS5A exists in two major phosphorylated forms, p56 and p58, with the phosphorylation status influencing RNA replication efficiency and protein interaction. It modulates multiple cellular signaling pathways, antagonizes innate immune responses, and is a validated target for direct acting antivirals (DAAs) used in treating chronic hepatitis C infection.

Inhibition of NS5A function, disrupting RNA replication and virion assembly