Chemical and Structural Aspects of Ebola Virus Entry Inhibitors

The Ebolaviruses are members of the family Filoviridae (“filoviruses”) and cause severe hemhorragic fever with human case fatality rates as high as 90%. Infection requires attachment of the viral particle to cells and triggering of membrane fusion between the host and viral membranes, a process that occurs in the host endosome and is facilitated by the envelope glycoprotein (GP). One potential strategy for therapeutic intervention is the development of agents (antibodies, peptides, and small molecules) that can interfere with viral entry aspects such as attachment, uptake, priming, or membrane fusion. This paper highlights recent developments in the discovery and evaluation of therapeutic entry inhibitors and identifies opportunities moving forward.