Evidence map›Paper›PMID 34927585›Full record

ArticleeLife2021

Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.

Tümay Capraz, Nikolaus F Kienzl, Elisabeth Laurent, Jan W Perthold, Esther Föderl-Höbenreich, Clemens Grünwald-Gruber, Daniel Maresch, Vanessa Monteil, Janine Niederhöfer, Gerald Wirnsberger and 6 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
  6. The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
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  14. Frontiers in bioengineering and biotechnology · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Engineering ACE2 decoy receptors to combat viral escapability.Trends in pharmacological sciences · 2022
    Review
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

16 authors at 5 institutions in 3 countries.

Tümay Capraz *Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0002-2547-067X
Nikolaus F Kienzl *Institute of Plant Biotechnology and Cell Biology, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0001-8057-3930
Elisabeth Laurent *Institute of Molecular Biotechnology, Department of Biotechnology and Core Facility Biomolecular & Cellular Analysis, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0002-5234-5524
Jan W PertholdInstitute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0002-8575-0278
Esther Föderl-HöbenreichDiagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.ORCID 0000-0003-2066-1036
Clemens Grünwald-GruberInstitute of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.ORCID 0000-0002-6097-8348
Daniel MareschInstitute of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.
Vanessa MonteilKarolinska Institute, Department of Laboratory Medicine, Stockholm, Sweden.ORCID 0000-0002-2652-5695
Janine NiederhöferApeiron Biologics, Vienna, Austria.
Gerald WirnsbergerApeiron Biologics, Vienna, Austria.ORCID 0000-0001-7035-7038
Ali MirazimiKarolinska Institute, Department of Laboratory Medicine, Stockholm, Sweden.
Kurt ZatloukalDiagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.ORCID 0000-0001-5299-7218
Lukas MachInstitute of Plant Biotechnology and Cell Biology, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0001-9013-5408
Josef M PenningerIMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr, Vienna, Austria.ORCID 0000-0002-8194-3777
Chris OostenbrinkInstitute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.ORCID 0000-0002-4232-2556
Johannes StadlmannInstitute of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.ORCID 0000-0001-5693-6690
BOKU University · ATInstitute of Molecular Biotechnology · ATApeiron Biologics (Austria) · ATKarolinska Institutet · SEMedical University of Graz · AT

Funding

Austrian Science Fund W1224-B09Austrian Science Fund Z271-B19Austrian Science Fund FWF W 1224Austrian Science Fund FWF Z 271Canada Research Chairs F18-0133CIHR F20-02015CIHR F20-02343DOC fellowship of the Academy of Sciences 24987Innovative Medicines Initiative 2 Joint Undertaking 101005026Vienna Science and Technology Fund COV20-015
6 · The paper itself

Abstract

Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells. Glycosylation of both proteins is critical for this interaction. Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19. We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation. Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein. Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.

Indexed as

Molecular Dynamics SimulationAngiotensin-Converting Enzyme 2COVID-19GlycosylationHumansPolysaccharidesProtein BindingProtein EngineeringReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationACE2 protein, humanAngiotensin-Converting Enzyme 2PolysaccharidesReceptors, VirusSpike Glycoprotein, CoronavirusACE2angiotensin converting enzyme 2biochemistrychemical biologyglycosylationhumanmolecular biophysicsSARS-CoV-2structural biologyviruses

Identifiers

PMID34927585
PMCPMC8730730
OpenAlexW4225966229

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.