Research Articlehepatitis C

Identification of a Class of HCV Inhibitors Directed Against the Nonstructural Protein NS4B

Science Translational Medicine  20 Jan 2010:
Vol. 2, Issue 15, pp. 15ra6
DOI: 10.1126/scitranslmed.3000331

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Editor's Summary

Hepatitis C is a surreptitious infection leading to inflammation of the liver, chronic liver disease, and ultimately causing cirrhosis. Nearly 150 million infected patients worldwide are in serious need of an alternative to viral suppressants in current use that have significant toxicities and are often ineffective. Cho and colleagues now take a closer look at the molecular virology of hepatitis C and identify a crucial new function for a largely uncharacterized protein, NS4B. They found that a particular region of this protein, which is critically involved in forming small vesicle aggregates that form the hypothesized platform to facilitate viral genome replication, can be manipulated to serve as a readout for high-throughput screens aimed at uncovering small-molecule pharmacological inhibitors of hepatitis C genome replication. Screening through a milieu of possibilities, they demonstrate the utility of two such compounds and tease apart the mechanism and biochemical activities by which these small inhibitors disrupt NS4B function and ultimately viral replication. Whether these new compounds can be used as monotherapies or in amalgamation with current strategies awaits further testing.


  • * These authors contributed equally to this work.

  • Citation: N.-J. Cho, H. Dvory-Sobol, C. Lee, S.-J. Cho, P. Bryson, M. Masek, M. Elazar, C. W. Frank, J. S. Glenn, Identification of a Class of HCV Inhibitors Directed Against the Nonstructural Protein NS4B. Sci. Transl. Med. 2, 15ra6 (2010).