Kilgore Paul E, Grabenstein John D, Salim Abdulbaset M, Rybak Michael
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan.
Pharmacotherapy. 2015 Jan;35(1):43-53. doi: 10.1002/phar.1545.
In March 2014, the largest Ebola outbreak in history exploded across West Africa. As of November 14, 2014, the World Health Organization has reported a total of 21,296 Ebola virus disease (EVD) cases, including 13,427 laboratory-confirmed EVD cases reported from the three most affected countries (Guinea, Liberia, and Sierra Leone). As the outbreak of EVD has spread, clinical disease severity and national EVD case-fatality rates have remained high (21.2-60.8%). Prior to 2013, several EVD outbreaks were controlled by using routine public health interventions; however, the widespread nature of the current EVD outbreak as well as cultural practices in the affected countries have challenged even the most active case identification efforts. In addition, although treatment centers provide supportive care, no effective therapeutic agents are available for EVD-endemic countries. The ongoing EVD outbreak has stimulated investigation of several different therapeutic strategies that target specific viral structures and mechanisms of Ebola viruses. Six to eight putative pharmacotherapies or immunologically based treatments have demonstrated promising results in animal studies. In addition, agents composed of small interfering RNAs targeting specific proteins of Ebola viruses, traditional hyperimmune globulin isolated from Ebola animal models, monoclonal antibodies, and morpholino oligomers (small molecules used to block viral gene expression). A number of EVD therapeutic agents are now entering accelerated human trials in EVD-endemic countries. The goal of therapeutic agent development includes postexposure prevention and EVD cure. As knowledge of Ebola virus virology and pathogenesis grows, it is likely that new therapeutic tools will be developed. Deployment of novel Ebola therapies will require unprecedented cooperation as well as investment to ensure that therapeutic tools become available to populations at greatest risk for EVD and its complications. In this article, we review several agents and strategies that are now under active development.
2014年3月，史上最大规模的埃博拉疫情在西非爆发。截至2014年11月14日，世界卫生组织报告埃博拉病毒病（EVD）病例总数达21296例，其中包括来自三个疫情最严重国家（几内亚、利比里亚和塞拉利昂）报告的13427例实验室确诊EVD病例。随着EVD疫情的蔓延，临床疾病严重程度和各国EVD病死率一直居高不下（21.2% - 60.8%）。在2013年之前，几起EVD疫情通过常规公共卫生干预措施得到了控制；然而，当前EVD疫情的广泛传播以及受影响国家的文化习俗，即使是最积极的病例识别工作也面临挑战。此外，尽管治疗中心提供支持性护理，但EVD流行国家尚无有效的治疗药物。持续的EVD疫情激发了针对埃博拉病毒特定病毒结构和机制的几种不同治疗策略的研究。六到八种假定的药物疗法或基于免疫的治疗方法在动物研究中已显示出有前景的结果。此外，还有针对埃博拉病毒特定蛋白的小分子干扰RNA制剂、从埃博拉动物模型中分离的传统高效价免疫球蛋白、单克隆抗体和吗啉代寡聚物（用于阻断病毒基因表达的小分子）。现在，许多EVD治疗药物正在EVD流行国家进入加速人体试验阶段。治疗药物开发的目标包括暴露后预防和治愈EVD。随着对埃博拉病毒病毒学和发病机制的了解不断增加，很可能会开发出新的治疗工具。部署新型埃博拉疗法将需要前所未有的合作以及投资，以确保治疗工具能够提供给面临EVD及其并发症风险最大的人群。在本文中，我们综述了几种目前正在积极研发的药物和策略。
