Lysosomotropic agents as HCV entry inhibitors

Usman A. Ashfaq, Tariq Javed, Sidra Rehman, Zafar Nawaz, Sheikh Riazuddin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH4Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH 4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.

Original languageEnglish
Article number163
JournalVirology Journal
Volume8
DOIs
StatePublished - Apr 18 2011

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Chloroquine
Endocytosis
Antiviral Agents
Liver
Genotype
Ammonium Chloride
Endosomes
Lysosomes
Luciferases
Toxicology
Proteins
Cell Proliferation
Cell Membrane
Viruses

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Ashfaq, U. A., Javed, T., Rehman, S., Nawaz, Z., & Riazuddin, S. (2011). Lysosomotropic agents as HCV entry inhibitors. Virology Journal, 8, [163]. https://doi.org/10.1186/1743-422X-8-163

Lysosomotropic agents as HCV entry inhibitors. / Ashfaq, Usman A.; Javed, Tariq; Rehman, Sidra; Nawaz, Zafar; Riazuddin, Sheikh.

In: Virology Journal, Vol. 8, 163, 18.04.2011.

Research output: Contribution to journalArticle

Ashfaq, Usman A. ; Javed, Tariq ; Rehman, Sidra ; Nawaz, Zafar ; Riazuddin, Sheikh. / Lysosomotropic agents as HCV entry inhibitors. In: Virology Journal. 2011 ; Vol. 8.
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