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Inhibitors of the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5B
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The Future of HCV Therapy: NS4B as an Antiviral Target

Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR 3115A, 269 Campus Drive, Palo Alto, CA, USA
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, USA
Veterans Administration Medical Center, 3801 Miranda Avenue, Palo Alto, CA, USA
Author to whom correspondence should be addressed.
Viruses 2010, 2(11), 2481-2492;
Received: 19 August 2010 / Revised: 28 September 2010 / Accepted: 13 October 2010 / Published: 10 November 2010
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
PDF [166 KB, uploaded 12 May 2015]


Chronic hepatitis C virus (HCV) infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors) are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B) protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM) domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.
Keywords: HCV; hepatitis C virus; antiviral agents; NS4B; clinical trials; RNA binding; amphipathic helix; NTPase HCV; hepatitis C virus; antiviral agents; NS4B; clinical trials; RNA binding; amphipathic helix; NTPase
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Dvory-Sobol, H.; Pang, P.S.; Glenn, J.S. The Future of HCV Therapy: NS4B as an Antiviral Target. Viruses 2010, 2, 2481-2492.

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