Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

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Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS

Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.

PubMed ID

26917592 [ View in PubMed

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Abstract

Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

DrugBank Data that Cites this Article

Drugs

Ansuvimab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ansuvimab	Envelope glycoprotein	Protein	Zaire ebolavirus (strain Mayinga-76)	Yes	Antagonist	Details