title: Fluoroquinolones inhibit HCV by targeting its helicase.
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.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Khan
authors.forename: Sammer
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Sadiq
authors.initials: S
authors.lastname: Rehmani
authors.forename: Shahana U
authors.initials: SU
authors.lastname: Kazmi
authors.forename: Syed H
authors.initials: SH
authors.lastname: Ali
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D024841:Fluoroquinolones / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D024841:Fluoroquinolones; D020365:RNA Helicases; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases