Use of Fluoroquinolones in Patients with Chronic Hepatitis C Virus-Induced Liver Failure

Kojima, Hiroshige; Kaita, Kelly; Hawkins, Kim; Uhanova, Julia; Gy, Minuk

doi:10.1128/aac.46.10.3280-3282.2002

Cited by 11 publications

(9 citation statements)

References 15 publications

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“…However in the last several years, a multitude of previously unsuspected effects of fluoroquinolones on eukaryotic cell functions have been revealed, including enhancement of RNAi [22][23][24], inhibition of cellular helicases [25,26], attenuation of cytokines and pro-inflammatory reactive oxygen species [27][28][29], and modification of apoptosis [30] and autophagy [31]. Furthermore, fluoroquinolones have been shown to suppress hepatitis C virus (HCV, family Flaviviridae) replication in vitro, possibly by inhibiting the viral helicase [32], but this suppression has not translated into an effective treatment for patients with liver failure due to chronic HCV infection [33]. Additionally, fluoroquinolones suppress rhinovirus infection by reducing expression of the viral receptor on cells [34].…”

Section: Introductionmentioning

confidence: 99%

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Scroggs

Andrade

Ramesh

et al. 2020

Viruses

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Repurposing FDA-approved compounds could provide the fastest route to alleviate the burden of disease caused by flaviviruses. In this study, three fluoroquinolones, enoxacin, difloxacin and ciprofloxacin, curtailed replication of flaviviruses Zika (ZIKV), dengue (DENV), Langat (LGTV) and Modoc (MODV) in HEK-293 cells at low micromolar concentrations. Time-of-addition assays suggested that enoxacin suppressed ZIKV replication at an intermediate step in the virus life cycle, whereas ciprofloxacin and difloxacin had a wider window of efficacy. A129 mice infected with 1 × 105 plaque-forming units (pfu) ZIKV FSS13025 (n = 20) or phosphate buffered saline (PBS) (n = 11) on day 0 and treated with enoxacin at 10 mg/kg or 15 mg/kg or diluent orally twice daily on days 1–5 did not differ in weight change or virus titer in serum or brain. However, mice treated with enoxacin showed a significant, five-fold decrease in ZIKV titer in testes relative to controls. Mice infected with 1 × 102 pfu ZIKV (n = 13) or PBS (n = 13) on day 0 and treated with 15 mg/kg oral enoxacin or diluent twice daily pre-treatment and days 1–5 post-treatment also did not differ in weight and viral load in the serum, brain, and liver, but mice treated with enoxacin showed a significant, 2.5-fold decrease in ZIKV titer in testes relative to controls. ZIKV can be sexually transmitted, so reduction of titer in the testes by enoxacin should be further investigated.

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Section: Introductionmentioning

confidence: 99%

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Scroggs

Andrade

Ramesh

et al. 2020

Viruses

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“…for 30 days. Serum HCV RNA levels remained largely unchanged in these patients [55]. The latter study indicates that the anti-HCVefficacy of quinolones may be limited in patients with advanced liver cirrhosis.…”

Section: Antiviral Activities Of Fluoroquinolonesmentioning

confidence: 65%

“…Ciprofloxacin, ofloxacin, levofloxacin, and gatifloxacin were found to be clinically effective in the treatment of the singlestranded RNA HCV and the non-enveloped, encapsulated DNA polyomavirus BK [54][55][56][57][58][59][60]. Five and four patients with HCV-induced chronic hepatitis and compensated liver cirrhosis, respectively, were treated with 100 to 900 mg ofloxacin per day for one to eight weeks.…”

Section: Antiviral Activities Of Fluoroquinolonesmentioning

confidence: 99%

Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

Dalhoff¹

2014

Eur J Clin Microbiol Infect Dis

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This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings.

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“…Previous studies assessing the efficacy of ofloxacin and ciprofloxacin in patients with chronic hepatitis C have produced conflicting results. Two pilot studies initially suggested a potential benefit of combining ofloxacin with IFN-a [28,29]; however, later trials recruiting a larger number of patients failed to reproduce these results convincingly [30,31]. Fluoroquinolones that have tested as highly potent in our experiment have not been tested on patients yet.…”

Section: Discussionmentioning

confidence: 92%

Fluoroquinolones Inhibit HCV by Targeting its Helicase

et al. 2011

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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-beaconbased 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.

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Use of Fluoroquinolones in Patients with Chronic Hepatitis C Virus-Induced Liver Failure

Cited by 11 publications

References 15 publications

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses

Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

Fluoroquinolones Inhibit HCV by Targeting its Helicase

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