Evidence map›Paper›PMID 33852862›Full record

ArticleCell reports2021

Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies.

Charles D Murin, Pavlo Gilchuk, Philipp A Ilinykh, Kai Huang, Natalia Kuzmina, Xiaoli Shen, Jessica F Bruhn, Aubrey L Bryan, Edgar Davidson, Benjamin J Doranz and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 1 country.

Charles D MurinDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pavlo GilchukVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Philipp A IlinykhGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Kai HuangGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Natalia KuzminaGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Xiaoli ShenGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Jessica F BruhnLaboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.
Aubrey L BryanIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Edgar DavidsonIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Benjamin J DoranzIntegral Molecular, Inc., Philadelphia, PA 19104, USA.
Lauren E WilliamsonDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jeffrey CoppsDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tanwee AlkutkarDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Andrew I FlyakDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Alexander BukreyevGalveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
James E CroweVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: andrew@scripps.edu.
Scripps Research Institute · USVanderbilt University Medical Center · USIntegral Molecular (United States) · USThe University of Texas Medical Branch at Galveston · USGalveston College · USSalk Institute for Biological Studies · US

Funding

Research Project 3: siRNA Therapy and Small Molecule Combination Treatment for FilovirusesU19AI142785 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GEISBERT, THOMAS WILLIAM · 2019 to 2023
$35.5M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Mechanistic Virology CoreU19AI109762 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI LAI, JONATHAN R. · 2014 to 2018
$29.6M
NIAID NIH HHS U19 AI109762NIAID NIH HHS U19 AI142785NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization are not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures of diverse glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLDs) to the glycan cap, which we call the MLD anchor and cradle. Antibodies that bind to the MLD cradle share common features, including use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form β-hairpin structures to mimic the MLD anchor, disrupt MLD attachment, destabilize GP quaternary structure, and block cleavage events required for receptor binding. Our results provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.

Indexed as

Amino Acid SequenceAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody SpecificityBinding SitesCryoelectron MicroscopyEbolavirusEpitopesFemaleHEK293 CellsHeLa CellsHemorrhagic Fever, EbolaHumansJurkat CellsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesPolysaccharidesViral Envelope Proteinsantibodyantibody therapeuticsbroadly neutralizingEbola virusebolavirusesfilovirusesglycan capmAb

Identifiers

PMID33852862
PMCPMC8133395
OpenAlexW3156948351

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.