{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hastie KM"],"funding":["United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)","European Research Council","NIAID NIH HHS","Medical Research Council","NCI NIH HHS","NIH HHS","NIGMS NIH HHS"],"pagination":["1293"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11791206"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP<sub>1,2</sub>) are the standard of care for Ebola virus disease (EVD). Anti-GP<sub>1,2</sub> mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP<sub>1,2</sub> epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk-MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP<sub>1,2</sub> that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 "],"journal":["Nature communications"],"pubmed_title":["Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP&lt;sub&gt;(1,2)&lt;/sub&gt; in a position elevated from the virion membrane."],"pmcid":["PMC11791206"],"funding_grant_id":["P41 GM103393","HHSN261201500003I","648432","U19 AI142790","W31P4Q-14-1-0010","75N91019D00024","HHSN261201500003C","HHSN272200700016I","S10 OD012289","HHSN272201400058C","MC_UP_1201/16","HHSN272201800013C"],"pubmed_authors":["Chennareddy C","Kawaoka Y","Salie ZL","Briggs JAG","Kuhn JH","Hastie KM","Grinyo A","Ahmed R","Worwa G","Xiong X","Norris MJ","Ke Z","Halfmann PJ","DeWald LE","Yu X","Hariharan C","Heinrich M","Schendel SL","Crozier I","McArdle S","Davidson E","Davis CW","Holbrook MR","Branco LM","Doranz B","Saphire EO"],"additional_accession":[]},"is_claimable":false,"name":"Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP&lt;sub&gt;(1,2)&lt;/sub&gt; in a position elevated from the virion membrane.","description":"Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP<sub>1,2</sub>) are the standard of care for Ebola virus disease (EVD). Anti-GP<sub>1,2</sub> mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP<sub>1,2</sub> epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk-MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP<sub>1,2</sub> that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-06-02T02:01:05.724Z","creation":"2025-04-06T00:24:07.218Z"},"accession":"S-EPMC11791206","cross_references":{"pubmed":["39900911"],"doi":["10.1038/s41467-025-56452-2"]}}