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.

中文翻译：

---

具有新技术的旧药：氟喹诺酮类药物抑制黄病毒复制的功效。

重新利用FDA批准的化合物可以提供减轻黄病毒引起的疾病负担的最快途径。在这项研究中，三种氟喹诺酮类药物（依诺沙星，地氟沙星和环丙沙星）在低微摩尔浓度下抑制了黄病毒Zika（ZIKV），登革热（DENV），Langat（LGTV）和Modoc（MODV）在HEK-293细胞中的复制。添加时间分析表明依诺沙星在病毒生命周期的中间阶段抑制了ZIKV复制，而环丙沙星和地氟沙星的疗效范围更广。A129小鼠感染了1×10 ^5个噬斑形成单位（pfu）ZIKV FSS13025（n = 20）或磷酸盐缓冲液（PBS）（n= 11）在第0天，并在第1至5天每天两次以10 mg / kg或15 mg / kg的依诺沙星或稀释剂口服治疗，在血清或大脑中体重变化或病毒滴度无差异。但是，用依诺沙星治疗的小鼠的睾丸ZIKV滴度相对于对照组显着降低了五倍。感染1×10 ² pfu ZIKV（n = 13）或PBS（n= 13）在第0天，治疗前和治疗后第1-5天每天两次用15 mg / kg口服依诺沙星或稀释剂治疗两次，血清，脑和肝脏的重量和病毒载量也没有差异，但是小鼠与依诺沙星治疗相比，睾丸中ZIKV滴度显着降低2.5倍。ZIKV可以通过性传播，因此应进一步研究依诺沙星降低睾丸滴度的方法。