Nonstructural protein 5A, Hepatitis C virus (NS5A)

Nonstructural protein 5A (NS5A) is a zinc-binding, membrane-associated, proline-rich phosphoprotein encoded by the Hepatitis C virus (HCV). It plays a crucial role in the replication of viral RNA by forming part of the HCV replication complex and coordinating the assembly of new viral particles. NS5A is notable for lacking intrinsic enzymatic activity; its multifaceted functions are mediated through interactions with a variety of viral and host-cell proteins. It has three domains, of which domain I is structured while II and III are intrinsically disordered, facilitating conformational flexibility and interaction versatility. NS5A also binds viral RNA, modulates host immune responses (especially interferon sensitivity), regulates gene expression, and controls HCV assembly and egress. Because of its essential role in the viral life cycle and its impact on host-pathogen interactions, NS5A is a major target for direct-acting antiviral drugs used to treat HCV infection. Drug resistance may arise via point mutations in NS5A (RASs), which poses a challenge for antiviral therapy.

Other names

NS5AHepatitis C virus nonstructural protein 5AHCV NS5A

Inhibition of viral RNA replication (NS5A inhibitors block viral replication by binding to NS5A and interfering with its function in the replication complex); Prevention of viral assembly and release (interference with assembly steps)