title: Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model.
abstract: OBJECTIVE
  To evaluate the antiviral potency of a new anti-hepatitis C virus (HCV) antiviral agent targeting the cellular autophagy machinery.
  
  
  METHODS
  Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices (2.7 × 10(6) cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant (multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription - polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays.
  
  
  RESULTS
  The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dose-dependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect (compared to hydroxychloroquine EC50 = 1.17 μmol/L).
  
  
  CONCLUSIONS
  Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dose-dependent manner without cytotoxic effect.
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lagaye
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Brun
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Jesintha
authors.initials: J
authors.lastname: Gaston
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Ruzena
authors.initials: R
authors.lastname: Stranska
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Camus
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Dubray
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Rousseau
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Pierre-Philippe
authors.initials: PP
authors.lastname: Massault
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Jerôme
authors.initials: J
authors.lastname: Courcambeck
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Firas
authors.initials: F
authors.lastname: Bassisi
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.affiliation: Sylvie Lagaye, Jesintha Gaston, Stanislas Pol, Institut Pasteur, INSERM U1223, 75015 Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
keywords: Autophagy; Hepatitis C virus; Host antiviral therapy; Quinoline derivative; Tissue culture