title: Exploring the importance of zinc binding and steric/hydrophobic factors in novel HCV replication inhibitors.
abstract: Several novel compounds have been identified that inhibit the replication of hepatitis C virus in a replicon assay with EC50 values as low as 0.6 μM. Lead compounds were modified to investigate the possible role that zinc binding may play in inhibitor efficacy. In addition, the structure-activity relationship was explored to increase inhibitor efficacy and possibly identify favorable interactions within the currently unknown inhibitor binding pocket. The rationale for inhibitor design and biological results are presented herein.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Talley
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Delang
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States. Electronic address: pjsmith@umbc.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Smith
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D009284:Naphthols; D011804:Quinolines; D017361:Viral Nonstructural Proteins; D015032:Zinc
keywords: Hepatitis C virus; Inhibitor; Zinc binding