RT Journal Article SR Electronic T1 Identification of a Class of HCV Inhibitors Directed Against the Nonstructural Protein NS4B JF Science Translational Medicine FD American Association for the Advancement of Science SP 15ra6 OP 15ra6 DO 10.1126/scitranslmed.3000331 VO 2 IS 15 A1 Cho, Nam-Joon A1 Dvory-Sobol, Hadas A1 Lee, Choongho A1 Cho, Sang-Joon A1 Bryson, Paul A1 Masek, Marilyn A1 Elazar, Menashe A1 Frank, Curtis W. A1 Glenn, Jeffrey S. YR 2010 UL http://stm.sciencemag.org/content/2/15/15ra6.abstract AB New classes of drugs are needed to combat hepatitis C virus (HCV), an important worldwide cause of liver disease. We describe an activity of a key domain, an amphipathic helix we termed 4BAH2, within a specific HCV nonstructural protein, NS4B. In addition to its proposed role in viral replication, we validate 4BAH2 as essential for HCV genome replication and identify first-generation small-molecule inhibitors of 4BAH2 that specifically prevent HCV replication within cells. Mechanistic studies reveal that the inhibitors target 4BAH2 function by preventing either 4BAH2 oligomerization or 4BAH2 membrane association. 4BAH2 inhibitors represent an additional class of compounds with potential to effectively treat HCV. Copyright © 2010, American Association for the Advancement of Science