Structural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop
PublisherNature Publishing Group
MetadataShow full item record
AbstractThe severity of the 2014–2016 ebolavirus outbreak in West Africa expedited clinical development of therapeutics and vaccines though the countermeasures on hand were largely monospecific and lacked efficacy against other ebolavirus species that previously emerged. Recent studies indicate that ebolavirus glycoprotein (GP) fusion loops are targets for cross-protective antibodies. Here we report the 3.72 Å resolution crystal structure of one such cross-protective antibody, CA45, bound to the ectodomain of Ebola virus (EBOV) GP. The CA45 epitope spans multiple faces of the fusion loop stem, across both GP1 and GP2 subunits, with ~68% of residues identical across > 99.5% of known ebolavirus isolates. Extensive antibody interactions within a pan-ebolavirus small-molecule inhibitor binding cavity on GP define this cavity as a novel site of immune vulnerability. The structure elucidates broad ebolavirus neutralization through a highly conserved epitope on GP and further enables rational design and development of broadly protective vaccines and therapeutics. Copyright 2018, The Author(s).
SponsorsThis work was supported by an Intramural Research Award from the University of Maryland and by MPower funds from the State of Maryland, the Advanced Photon Source, Argonne National Laboratory, the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract Number W-31-109-Eng-38 and NIAID/NIH grant R01AI126587.
Keywordglycoprotein fusion loop
Hemorrhagic Fever, Ebola--prevention & control
Viral Fusion Proteins
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85054081877&doi=10.1038%2fs41467-018-06113-4&partnerID=40&md5=7d63ab65dd52d6b6e8acd47feeaccfae; http://hdl.handle.net/10713/9401
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