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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/9/1022 |
| _version_ | 1827706275182411776 |
|---|---|
| author | Stacey L. P. Scroggs Christy C. Andrade Ramesh Chinnasamy Sasha R. Azar Erin E. Schirtzinger Erin I. Garcia Jeffrey B. Arterburn Kathryn A. Hanley Shannan L. Rossi |
| author_facet | Stacey L. P. Scroggs Christy C. Andrade Ramesh Chinnasamy Sasha R. Azar Erin E. Schirtzinger Erin I. Garcia Jeffrey B. Arterburn Kathryn A. Hanley Shannan L. Rossi |
| author_sort | Stacey L. P. Scroggs |
| collection | DOAJ |
| 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<sup>5</sup> plaque-forming units (pfu) ZIKV FSS13025 (<i>n</i> = 20) or phosphate buffered saline (PBS) (<i>n</i> = 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<sup>2</sup> pfu ZIKV (<i>n</i> = 13) or PBS (<i>n</i> = 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. |
| first_indexed | 2024-03-10T16:22:15Z |
| format | Article |
| id | doaj.art-1ab7b3d2e4044ce293442d9277281551 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T16:22:15Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1ab7b3d2e4044ce293442d92772815512023-11-20T13:34:25ZengMDPI AGViruses1999-49152020-09-01129102210.3390/v12091022Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of FlavivirusesStacey L. P. Scroggs0Christy C. Andrade1Ramesh Chinnasamy2Sasha R. Azar3Erin E. Schirtzinger4Erin I. Garcia5Jeffrey B. Arterburn6Kathryn A. Hanley7Shannan L. Rossi8Department of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USAInstitute for Translational Sciences, The University of University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USADepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USARepurposing 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<sup>5</sup> plaque-forming units (pfu) ZIKV FSS13025 (<i>n</i> = 20) or phosphate buffered saline (PBS) (<i>n</i> = 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<sup>2</sup> pfu ZIKV (<i>n</i> = 13) or PBS (<i>n</i> = 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.https://www.mdpi.com/1999-4915/12/9/1022Zika virusdengue virusflavivirusantiviralfluoroquinoloneciprofloxacin |
| spellingShingle | Stacey L. P. Scroggs Christy C. Andrade Ramesh Chinnasamy Sasha R. Azar Erin E. Schirtzinger Erin I. Garcia Jeffrey B. Arterburn Kathryn A. Hanley Shannan L. Rossi Old Drugs with New Tricks: Efficacy of Fluoroquinolones to Suppress Replication of Flaviviruses Viruses Zika virus dengue virus flavivirus antiviral fluoroquinolone ciprofloxacin |
| 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 | Zika virus dengue virus flavivirus antiviral fluoroquinolone ciprofloxacin |
| url | https://www.mdpi.com/1999-4915/12/9/1022 |
| work_keys_str_mv | AT staceylpscroggs olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT christycandrade olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT rameshchinnasamy olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT sasharazar olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT erineschirtzinger olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT erinigarcia olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT jeffreybarterburn olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT kathrynahanley olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses AT shannanlrossi olddrugswithnewtricksefficacyoffluoroquinolonestosuppressreplicationofflaviviruses |