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Article

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

1
Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA
2
Biology of Vector-Borne Viruses Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
3
Department of Biology, Gonzaga University, Spokane, WA 99258, USA
4
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA
5
Institute for Translational Sciences, The University of University of Texas Medical Branch, Galveston, TX 77555, USA
6
Arthropod-borne Animal Diseases Research Unit, United States Department of Agriculture, Agricultural Research Service, Manhattan, KS 66506, USA
7
Science News, Washington, DC 20036, USA
8
Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Received: 24 August 2020 / Revised: 10 September 2020 / Accepted: 11 September 2020 / Published: 13 September 2020
(This article belongs to the Special Issue Drug-Repositioning Opportunities for Antiviral Therapy)
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. View Full-Text
Keywords: Zika virus; dengue virus; flavivirus; antiviral; fluoroquinolone; ciprofloxacin; enoxacin; difloxacin; A129 mouse; testis Zika virus; dengue virus; flavivirus; antiviral; fluoroquinolone; ciprofloxacin; enoxacin; difloxacin; A129 mouse; testis
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MDPI and ACS Style

Scroggs, S.L.P.; Andrade, C.C.; Chinnasamy, R.; Azar, S.R.; Schirtzinger, E.E.; Garcia, E.I.; Arterburn, J.B.; Hanley, K.A.; Rossi, S.L. Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses. Viruses 2020, 12, 1022. https://0-doi-org.brum.beds.ac.uk/10.3390/v12091022

AMA Style

Scroggs SLP, Andrade CC, Chinnasamy R, Azar SR, Schirtzinger EE, Garcia EI, Arterburn JB, Hanley KA, Rossi SL. Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses. Viruses. 2020; 12(9):1022. https://0-doi-org.brum.beds.ac.uk/10.3390/v12091022

Chicago/Turabian Style

Scroggs, Stacey L.P., Christy C. Andrade, Ramesh Chinnasamy, Sasha R. Azar, Erin E. Schirtzinger, Erin I. Garcia, Jeffrey B. Arterburn, Kathryn A. Hanley, and Shannan L. Rossi 2020. "Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses" Viruses 12, no. 9: 1022. https://0-doi-org.brum.beds.ac.uk/10.3390/v12091022

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