Targeting Ebola virus replication through pharmaceutical intervention

Introduction. The consistent emergence/reemergence of filoviruses into a world that previously lacked an approved pharmaceutical intervention parallels an experience repeatedly played-out for most other emerging pathogenic zoonotic viruses. Investment to preemptively develop effective and low-cost prophylactic and therapeutic interventions against viruses that have high potential for emergence and societal impact should be a priority. Areas covered. Candidate drugs can be characterized into those that interfere with cellular processes required for Ebola virus (EBOV) replication (host-directed), and those that directly target virally encoded functions (direct-acting). We discuss strategies to identify pharmaceutical interventions for EBOV infections. PubMed/Web of Science databases were searched to establish a detailed catalog of these interventions. Expert opinion. Many drug candidates show promising in vitro inhibitory activity, but experience with EBOV shows the general lack of translation to in vivo efficacy for host-directed repurposed drugs. Better translation is seen for direct-acting antivirals, in particular monoclonal antibodies. The FDA-approved monoclonal antibody treatment, Inmazeb (TM) is a success story that could be improved in terms of impact on EBOV-associated disease and mortality, possibly by combination with other direct-acting agents targeting distinct aspects of the viral replication cycle. Costs need to be addressed given EBOV emergence primarily in under-resourced countries.