Horizon Discovery Inc., 245 First Street, Cambridge, MA 02142, USA.
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
Sci Transl Med. 2015 Jun 3;7(290):290ra89. doi: 10.1126/scitranslmed.aaa5597.
Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.
目前，尚无批准的疗法可用于治疗或预防埃博拉病毒引起的感染，最近的事件表明迫切需要快速发现新的治疗方法。重新利用已批准用于新兴感染的药物仍然是潜在抗病毒疗法的重要资源。我们使用体外感染测定法测试了约 2600 种已批准的药物和分子探针，该测定法使用的是物种 Zaire ebolavirus。发现了 80 种美国食品和药物管理局批准的药物具有选择性抗病毒活性，这些药物涵盖了多种作用机制类别，包括选择性雌激素受体调节剂、抗组胺药、钙通道阻滞剂和抗抑郁药。使用体内埃博拉病毒感染模型进行的结果证实了几种药物（如 bepridil 和 sertraline）的保护能力。病毒进入测定表明，这些抗病毒药物中的大多数都能阻断病毒进入的晚期阶段。由于它们已获得批准，这些药物有可能迅速推向临床，并作为埃博拉病毒感染的治疗对策使用。
