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

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...

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Autores principales: Scroggs, Stacey L. P., Andrade, Christy C., Chinnasamy, Ramesh, Azar, Sasha R., Schirtzinger, Erin E., Garcia, Erin I., Arterburn, Jeffrey B., Hanley, Kathryn A., Rossi, Shannan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551155/
https://www.ncbi.nlm.nih.gov/pubmed/32933138
http://dx.doi.org/10.3390/v12091022
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author Scroggs, Stacey L. P.
Andrade, Christy C.
Chinnasamy, Ramesh
Azar, Sasha R.
Schirtzinger, Erin E.
Garcia, Erin I.
Arterburn, Jeffrey B.
Hanley, Kathryn A.
Rossi, Shannan L.
author_facet Scroggs, Stacey L. P.
Andrade, Christy C.
Chinnasamy, Ramesh
Azar, Sasha R.
Schirtzinger, Erin E.
Garcia, Erin I.
Arterburn, Jeffrey B.
Hanley, Kathryn A.
Rossi, Shannan L.
author_sort Scroggs, Stacey L. P.
collection PubMed
description 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 × 10(5) 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 × 10(2) 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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spelling pubmed-75511552020-10-16 Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses Scroggs, Stacey L. P. Andrade, Christy C. Chinnasamy, Ramesh Azar, Sasha R. Schirtzinger, Erin E. Garcia, Erin I. Arterburn, Jeffrey B. Hanley, Kathryn A. Rossi, Shannan L. Viruses Article 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 × 10(5) 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 × 10(2) 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. MDPI 2020-09-13 /pmc/articles/PMC7551155/ /pubmed/32933138 http://dx.doi.org/10.3390/v12091022 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scroggs, Stacey L. P.
Andrade, Christy C.
Chinnasamy, Ramesh
Azar, Sasha R.
Schirtzinger, Erin E.
Garcia, Erin I.
Arterburn, Jeffrey B.
Hanley, Kathryn A.
Rossi, Shannan L.
Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title_full Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title_fullStr Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title_full_unstemmed Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title_short Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses
title_sort old drugs with new tricks: efficacy of fluoroquinolones to suppress replication of flaviviruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551155/
https://www.ncbi.nlm.nih.gov/pubmed/32933138
http://dx.doi.org/10.3390/v12091022
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