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The discovery and development of novel treatment strategies for filoviruses

ABSTRACT Introduction Filoviruses are negative-stranded, enveloped RNA viruses that can cause hemorrhagic fever in humans and include Ebola and Marburg viruses. Lethality rates can reach 90% in isolated outbreaks. The 2013–2016 Ebola virus epidemic demonstrated the global threat of filoviruses and hastened development of vaccines and therapeutics. There are six known filoviruses that cause disease in humans, but still few therapeutics are available for treatment. Areas covered This review summarizes identification, testing, and development of therapeutics based on the peer-reviewed scientific literature beginning with the discovery of filoviruses in 1967. Small molecules, antibodies, cytokines, antisense, post-exposure vaccination, and host-targeted therapeutic approaches are discussed. An emphasis is placed on therapeutics that have shown promise in in vivo studies. Expert opinion Two monoclonal antibody regimens are approved for use in humans for one filovirus (Ebola virus), and preclinical nonhuman primate studies suggest that other monoclonal-based therapies are likely to be effective against other filoviruses. Significant progress has been made in small-molecule antivirals and host-targeted approaches. An important consideration is the necessity of pan-filovirus therapeutics via broadly effective small molecules, antibody cocktails, and cross-reactive antibodies. The use of filovirus therapeutics as prophylactic treatment or in chronically infected individuals should be considered.