The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein

Choongho Lee, Han Ma, Julie Qi Hang, Vincent Leveque, Ella H. Sklan, Menashe Elazar, Klaus Klumpp, Jeffrey S. Glenn

Research output: Contribution to journalArticlepeer-review

Abstract

The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalVirology
Volume414
Issue number1
DOIs
StatePublished - 25 May 2011

Keywords

  • Anti-HCV compounds
  • BMS-790052
  • Hepatitis c virus
  • NS5A inhibitor
  • NS5A protein
  • Replication complex

Fingerprint

Dive into the research topics of 'The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein'. Together they form a unique fingerprint.

Cite this