PT  - JOURNAL ARTICLE
AU  - Cho, Nam-Joon
AU  - Dvory-Sobol, Hadas
AU  - Lee, Choongho
AU  - Cho, Sang-Joon
AU  - Bryson, Paul
AU  - Masek, Marilyn
AU  - Elazar, Menashe
AU  - Frank, Curtis W.
AU  - Glenn, Jeffrey S.
TI  - Identification of a Class of HCV Inhibitors Directed Against the Nonstructural Protein NS4B
AID  - 10.1126/scitranslmed.3000331
DP  - 2010 Jan 20
TA  - Science Translational Medicine
PG  - 15ra6--15ra6
VI  - 2
IP  - 15
4099  - http://stm.sciencemag.org/content/2/15/15ra6.short
4100  - http://stm.sciencemag.org/content/2/15/15ra6.full
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