Fluoroquinolones inhibit HCV by targeting its helicase

Irfan A. Khan, Sammer Siddiqui, Sadiq Rehmani, Shahana U. Kazmi, Syed H. Ali

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: HCV has infected >170 million individuals worldwide. Effective therapy against HCV is still lacking and there is a need to develop potent drugs against the virus. In the present study, we have employed two culture models to test the activity of fluoroquinolone drugs against HCV: a subgenomic replicon that is able to replicate independently in the cell line Huh-8 and the Huh-7 cell culture model that employs cells transfected with synthetic HCV RNA to produce the infectious HCV particles. Fluoroquinolones have also been shown to have inhibitory activity against certain viruses, possibly by targeting the viral helicase. To tease out the mechanism of the antiviral activity of fluoroquinolones, their effect on HCV NS3 helicase protein was also tested. Methods: Huh-7 cells producing the HCV virion as well as Huh-8 cells were grown in the presence or absence of 12 different fluoroquinolones. Afterwards, Huh-7 and Huh-8 cells were lysed and viral RNA was extracted. The extracted RNA was reverse transcribed and quantified by real-time quantitative PCR. Fluoroquinolones were also tested on purified NS3 protein in a molecular-beacon-based in vitro helicase assay. Results: To varying degrees, all of the tested fluoroquinolones effectively inhibited HCV replication in both Huh-7 and Huh-8 culture models. The inhibition of HCV NS3 helicase activity was also observed with all 12 of the fluoroquinolones. Conclusions: Fluoroquinolones inhibit HCV replication possibly by targeting the HCV NS3 helicase. These drugs hold promise for the treatment of HCV infection.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalAntiviral Therapy
Volume17
Issue number3
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Fluoroquinolones
Pharmaceutical Preparations
RNA
Viruses
Replicon
Viral RNA
Virion
Antiviral Agents
Real-Time Polymerase Chain Reaction
Proteins
Cell Culture Techniques
Cell Line
Infection

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Khan, I. A., Siddiqui, S., Rehmani, S., Kazmi, S. U., & Ali, S. H. (2012). Fluoroquinolones inhibit HCV by targeting its helicase. Antiviral Therapy, 17(3), 467-476. https://doi.org/10.3851/IMP1937

Fluoroquinolones inhibit HCV by targeting its helicase. / Khan, Irfan A.; Siddiqui, Sammer; Rehmani, Sadiq; Kazmi, Shahana U.; Ali, Syed H.

In: Antiviral Therapy, Vol. 17, No. 3, 2012, p. 467-476.

Research output: Contribution to journalArticle

Khan, IA, Siddiqui, S, Rehmani, S, Kazmi, SU & Ali, SH 2012, 'Fluoroquinolones inhibit HCV by targeting its helicase', Antiviral Therapy, vol. 17, no. 3, pp. 467-476. https://doi.org/10.3851/IMP1937
Khan, Irfan A. ; Siddiqui, Sammer ; Rehmani, Sadiq ; Kazmi, Shahana U. ; Ali, Syed H. / Fluoroquinolones inhibit HCV by targeting its helicase. In: Antiviral Therapy. 2012 ; Vol. 17, No. 3. pp. 467-476.
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