2. Academic Validation
  3. UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication

UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication

  • Bioorg Med Chem Lett. 2014 Jan 15;24(2):609-12. doi: 10.1016/j.bmcl.2013.12.012.
Dawn N Ward 1,  Daniel C Talley 1,  Mrinalini Tavag 1,  Samrawit Menji 1,  Paul Schaughency 1,  Andrea Baier 2,  Paul J Smith 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
  • 2 Department of Molecular Biology, John Paul II Catholic University of Lublin, Poland.
  • 3 Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States. Electronic address: [email protected].
PMID: 24360997 DOI: 10.1016/j.bmcl.2013.12.012
Abstract

The Bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50 μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor-enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein.

Keywords

Helicase; Hepatitis C; Inhibitor; NS3.

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