Summary



The Outsmart Ebola Together research team has conducted an enormous number of virtual docking experiments, and they are now ready to embark on a new stage of their research.



The Ebola virus killed many thousands of people in 2014 during the largest outbreak of the disease since it was first discovered in 1976. Significantly, research has shown that the virus's long incubation period and our highly connected modern world could allow the virus to spread to new geographies and across oceans. Currently, there are no approved treatments or vaccines for this deadly disease, and the search for an effective antiviral drug to treat the disease is a high priority.

Outsmart Ebola Together is now approaching completion of its first phase, having conducted hundreds of thousands of docking computations. In this phase, we have simulated the binding of potential small-molecule drugs against atomic structures of proteins of the filovirus family. We have in particular targeted the receptor binding site (RBS) of the Ebola virus glycoprotein (GP), which plays a key role in viral entry into human cells.

For Ebola to infect a human cell, the RBS must bind to a receptor in the cell membrane, thereby infiltrating the GP into one of the inner cellular compartments, known as the endosome. Once inside the endosome, the presence of enzymes and an acidic environment transform the molecular structure of GP, allowing it to fuse with the endosome wall and so gain entry to the cytoplasm.

Our study now expands to consider multiple stages in the dynamic molecular transformations of GP and other Ebola proteins. These transformations are essential to the viral life cycle, and therefore represent an ideal target for the design of effective antiviral drugs.

Thank you to all volunteers who have supported this project.