Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
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.
Viruses. 2020 Sep 13;12(9):1022. doi: 10.3390/v12091022.
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 plaque-forming units (pfu) ZIKV FSS13025 ( = 20) or phosphate buffered saline (PBS) ( = 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 pfu ZIKV ( = 13) or PBS ( = 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.
重新利用已获美国食品药品监督管理局批准的化合物可能为缓解黄病毒引起的疾病负担提供最快的途径。在这项研究中，三种氟喹诺酮类药物依诺沙星、二氟沙星和环丙沙星，以低微摩尔浓度在 HEK-293 细胞中抑制了黄病毒寨卡病毒（ZIKV）、登革热病毒（DENV）、兰加特病毒（LGTV）和莫多克病毒（MODV）的复制。添加时间测定表明，依诺沙星在病毒生命周期的中间步骤中抑制 ZIKV 复制，而环丙沙星和二氟沙星的疗效范围更广。在第 0 天用 1×10 噬斑形成单位（pfu）ZIKV FSS13025（ = 20）或磷酸盐缓冲盐水（PBS）（ = 11）感染 A129 小鼠，然后在第 1-5 天每天口服 10mg/kg 或 15mg/kg 依诺沙星或稀释剂两次，体重变化或血清或脑中的病毒滴度无差异。然而，与对照组相比，用依诺沙星治疗的小鼠睾丸中的 ZIKV 滴度显著降低了五倍。在第 0 天用 1×10 pfu ZIKV（ = 13）或 PBS（ = 13）感染 A129 小鼠，然后在预处理和第 1-5 天每天两次口服 15mg/kg 依诺沙星或稀释剂，体重和血清、脑和肝中的病毒载量无差异，但用依诺沙星治疗的小鼠睾丸中的 ZIKV 滴度显著降低了 2.5 倍，与对照组相比。ZIKV 可以通过性传播，因此，依诺沙星降低睾丸中的病毒滴度应进一步研究。
