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Lysosomotropic agents as HCV entry inhibitors.

Usman A Ashfaq1, Tariq Javed, Sidra Rehman

  • 1Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.com

Virology Journal
|April 13, 2011
PubMed
Summary

Lysosomotropic agents like Chloroquine and Ammonium chloride inhibit Hepatitis C virus (HCV) entry by increasing lysosomal pH. These agents reduced HCV pseudoparticle infectivity, suggesting a potential treatment strategy for chronic HCV.

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Area of Science:

  • Virology
  • Cell Biology
  • Pharmacology

Background:

  • Hepatitis C virus (HCV) entry into host cells involves envelope proteins E1 and E2.
  • HCV entry occurs via direct plasma membrane fusion or receptor-mediated endocytosis, with fusion triggered by low endosomal pH.

Purpose of the Study:

  • To investigate the antiviral effects of lysosomotropic agents (Chloroquine and Ammonium chloride) on pH-dependent HCV endocytosis.
  • To evaluate the potential of these agents in inhibiting HCV infection by modulating intracellular pH.

Main Methods:

  • HCV pseudoparticles (HCVpp) of genotypes 1a and 3a were produced and used to infect liver cells.
  • Cytotoxicity of Chloroquine and NH4Cl was assessed using MTT assay.
  • Antiviral activity was determined by measuring luciferase activity in infected cells treated with varying concentrations of the agents.

Main Results:

  • Chloroquine and Ammonium chloride demonstrated over 50% reduction in HCVpp infectivity.
  • Effective concentrations were 50 μM for Chloroquine and 10 mM for Ammonium chloride.
  • No significant cytotoxicity was observed at these effective concentrations.

Conclusions:

  • Lysosomotropic agents can inhibit HCV entry by increasing lysosomal pH, thereby interfering with the fusion step.
  • Modulating lysosomal pH presents a promising therapeutic strategy for treating chronic Hepatitis C virus infections.