Identification of a class of HCV inhibitors directed against the nonstructural protein NS4B

Nam Joon Cho; Hadas Dvory-Sobol; Choongho Lee; Sang Joon Cho; Paul Bryson; Marilyn Masek; Menashe Elazar; Curtis W. Frank; Jeffrey S. Glenn

doi:10.1126/scitranslmed.3000331

Identification of a class of HCV inhibitors directed against the nonstructural protein NS4B

Nam Joon Cho, Hadas Dvory-Sobol, Choongho Lee, Sang Joon Cho, Paul Bryson, Marilyn Masek, Menashe Elazar, Curtis W. Frank, Jeffrey S. Glenn

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	15ra6
Journal	Science Translational Medicine
Volume	2
Issue number	15
DOIs	https://doi.org/10.1126/scitranslmed.3000331
State	Published - 2010

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abstract = "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.",

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AU - Dvory-Sobol, Hadas

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AU - Bryson, Paul

AU - Masek, Marilyn

AU - Elazar, Menashe

AU - Frank, Curtis W.

AU - Glenn, Jeffrey S.

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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.

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Identification of a class of HCV inhibitors directed against the nonstructural protein NS4B

Abstract

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