Hepatitis C virus non-structural protein NS4B (NS4B)

Hepatitis C virus non-structural protein NS4B is a 27 kDa hydrophobic integral membrane protein that plays a central role in the viral replication cycle. Its primary function is the induction of the "membranous web," a specialized intracellular structure derived from the endoplasmic reticulum that serves as a protected scaffold for the viral replication complex. Beyond its structural role, NS4B possesses intrinsic enzymatic activities, including NTPase (GTPase and ATPase) functions and RNA-binding capabilities, both of which are essential for efficient viral genome synthesis. NS4B also interacts with host cell pathways, such as the unfolded protein response (UPR) and ER stress signaling, to create an environment conducive to viral persistence. Although most currently approved direct-acting antivirals (DAAs) target the NS3 protease or NS5A/NS5B proteins, NS4B remains a significant therapeutic target due to its essential role in organizing the replication machinery. Experimental inhibitors like clemizole have demonstrated the potential to disrupt NS4B-RNA interactions, offering a distinct mechanism for inhibiting viral replication and overcoming resistance to other DAA classes.

Other names

NS4BNon-structural protein 4Bp27HCV NS4B

Inhibition of viral RNA binding to NS4B, disruption of the membranous web replication platform, and inhibition of NTPase-mediated viral replication.