2. Academic Validation
  3. In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase

In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase

  • Eur J Med Chem. 2017 Jan 5:125:1115-1131. doi: 10.1016/j.ejmech.2016.10.043.
Marcella Bassetto 1,  Pieter Leyssen 2,  Johan Neyts 2,  Mark M Yerukhimovich 3,  David N Frick 3,  Matthew Courtney-Smith 4,  Andrea Brancale 4
Affiliations

Affiliations

  • 1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK. Electronic address: bassettom@cardiff.ac.uk.
  • 2 Rega Institute for Medical Research, University of Leuven, Belgium.
  • 3 Department of Chemistry & Biochemistry, University of Wisconsin- Milwaukee, Milwaukee, WI 53211, United States.
  • 4 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff CF103NB, UK.
PMID: 27810598 DOI: 10.1016/j.ejmech.2016.10.043
Abstract

A structure-based virtual screening of commercial compounds was carried out on the HCV NS3 helicase structure, with the aim to identify novel inhibitors of HCV replication. Among a selection of 13 commercial structures, one compound was found to inhibit the subgenomic HCV replicon in the low micromolar range. Different series of new piperazine-based analogues were designed and synthesised, and among them, several novel structures exhibited Antiviral activity in the HCV replicon assay. Some of the new compounds were also found to inhibit HCV NS3 helicase function in vitro, and one directly bound NS3 with a dissociation constant of 570 ± 270 nM.

Keywords

Anti-HCV activity; HCV NS3-helicase; NS3 helicase inhibitors; Piperazine derivatives; Structure-based virtual screening.

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