Exploring the importance of zinc binding and steric/hydrophobic factors in novel HCV replication inhibitors

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 mu M. 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. (C) 2016 Elsevier Ltd. All rights reserved.