Contemporary Anti-Ebola Drug Discovery Approaches and Platforms

The Ebola virus has a grave potential to destabilize civil society as we know it. The past few deadly Ebola outbreaks were unprecedented in size: The 2014-15 Ebola West Africa outbreak saw the virus spread from the epicenter through to Guinea, Sierra Leone, Nigeria, Congo, and Liberia. The 2014-15 Ebola West Africa outbreak was associated with almost 30,000 suspected or confirmed cases and over 11,000 documented deaths. The more recent 2018 outbreak in the Democratic Republic of Congo has so far resulted in 216 suspected or confirmed cases and 139 deaths. There is a general acceptance within the World Health Organization (WHO) and the Ebola outbreak response community that future outbreaks will become increasingly more frequent and more likely to involve intercontinental transmission. The magnitude of the recent outbreaks demonstrated in dramatic fashion the shortcomings of our mass casualty disease response capabilities and lack of therapeutic modalities for supporting Ebola outbreak prevention and control. Currently, there are no approved drugs although vaccines for human Ebola virus infection are in the trial phases and some potential treatments have been field tested most recently in the Congo Ebola outbreak. Treatment is limited to pain management and supportive care to counter dehydration and lack of oxygen. This underscores the critical need for effective antiviral drugs that specifically target this deadly disease. This review examines the current approaches for the discovery of anti-Ebola small molecule or biological therapeutics, their viral targets, mode of action, and contemporary platforms, which collectively form the backbone of the anti-Ebola drug discovery pipeline.