Tenacious Researchers Identify a Weakness in All Ebolaviruses

The Ebolavirus genus has at least five members, four of which are known to cause deadly disease in humans. An ideal therapy or a vaccine would protect against all ebolaviruses, but identifying a common weakness in all of them has remained elusive. West et al. [B. R. West, C. L. Moyer, L. B. King, M. L. Fusco, et al., mBio 9(5):e01674-18, 2018, https://doi.org/10.1128/mBio.01674-18] make the exciting discovery of an “Achilles’ heel,” a cryptic and conserved pocket, on the surface antigen glycoprotein (GP) that is nearly identical in all known ebolaviruses. Key to this discovery was their study of antibody ADI-15878, the only isolated human antibody that can block infectivity of all known ebolaviruses. Following tenacious efforts in X-ray crystallography, West et al. report the high-resolution crystal structures of the Ebola virus GP and the Bundibugyo virus GP, each bound to antibody ADI-15878. These structures reveal a highly conserved but partially obscured site on the virus GP, providing a foundation for design of vaccine antigens or antiviral therapies.