Therapeutic Targets of Ebola Virus Entry
Ebola is a category A hemorrhagic fever virus for which there are currently no approved vaccines or anti-virals. Recent success supports the concept of using small molecules to block the first stages of infection by enveloped viruses: binding to host cells and fusion with cellular membranes.
The long-term objective of our work is to develop small molecules that block binding and/or fusion of Ebola virus with host cells. Our approach to identify binding inhibitors is based on our recent demonstration that the Ebola glycoprotein (GP) is primed for fusion activation by cleavage of the native GP1 (130kD) binding subunit (by endosomal cathepsins) to an ~19kD fragment that retains full binding competency. The specific aims for the current year are: (1) to produce and test whether a recombinant Ebola GP1 receptor binding domain (RBD; e.g., a recombinant form of 19kD GP1) specifically inhibits Ebola virus entry and (2) to develop an assay with which to screen for inhibitors of GP-mediated binding.
Judith M. White, Ph.D.
University of Virginia