@article{24f4a09ab81d42339489c0c26ea2d52f,
title = "Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk",
abstract = "Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions.",
author = "King, {Liam B.} and West, {Brandyn R.} and Moyer, {Crystal L.} and Pavlo Gilchuk and Andrew Flyak and Ilinykh, {Philipp A.} and Robin Bombardi and Sean Hui and Kai Huang and Alexander Bukreyev and Crowe, {James E.} and Saphire, {Erica Ollmann}",
note = "Funding Information: We acknowledge support by NIH/NIAID U19 109762 (EOS), U19 AI109711 (to J.E.C. and A.B.), Defense Threat Reduction Agency grant HDTRA1-13-1-0034 (to J.E.C. and A. B.), and NIH/NIAID F30 AI136410 (L.B.K.). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC-02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. We thank Sharon Schendel for manuscript editing. This is manuscript # 29723 of The Scripps Research Institute. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-09732-7",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}