Post-exposure treatments for Ebola and Marburg virus infections

Key Points The filoviruses, Ebola virus and Marburg virus, cause lethal haemorrhagic fever in humans and non-human primates (NHPs), and there are currently no licensed vaccines or treatments available for human use. Death occurs in 90% or more of patients infected with Zaire ebolavirus (EBOV) if the viral load exceeds 6 log genome copies per millilitre in untreated patients, so antiviral interventions must be initiated early in the disease course. Among the post-exposure treatments and therapies developed to date against filoviruses, the monoclonal antibody-based approaches targeting filovirus glycoproteins appear to demonstrate the highest level of protective efficacy. Antisense approaches including small interfering RNAs and phosphorodiamidate morpholino oligomers have shown efficacy in NHP models of filovirus infection, and the modular nature of these technologies offers flexibility should mutations in a filovirus occur or a new filovirus be identified. Although preclinical data are sparse, the broad-spectrum antivirals favipiravir and GS-5734 have a number of advantages as interventions for filovirus infections, and their efficacy is not likely to be affected by mutations in a filovirus or the emergence of a previously unknown filovirus. The importance of advanced supportive care, including electrolyte balance, ventilation and dialysis, was likely pivotal in the success of treating EBOV-infected individuals in developed countries during the 2013–2016 EBOV epidemic. Efforts towards developing post-exposure therapies for infections with filoviruses, particularly Ebola and Marburg viruses, increased substantially during the Ebola virus outbreak of 2013–2016. Geisbert and colleagues review the progress made on this front and discuss the challenges and opportunities for developing post-exposure therapies in the future. The filoviruses — Ebola virus and Marburg virus — cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013–2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of