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Record W4283803757 · doi:10.15252/emmm.202115230

Clinical grade ACE2 as a universal agent to block SARS‐CoV‐2 variants

2022· article· en· W4283803757 on OpenAlexafffund
Vanessa Monteil, Brett Eaton, Elena Postnikova, Michael Murphy, Benedict Braunsfeld, Ian Crozier, Franz Kricek, Janine Niederhöfer, Alice Schwarzböck, Helene Breid, Stéphanie Devignot, Jonas Klingström, Charlotte Thålin, Max J. Kellner, Wanda Christ, Sebastian Havervall, Stefan Mereiter, Sylvia Knapp, Anna Sanchez Jimenez, Agnes Bugajska‐Schretter, Alexander Dohnal, Christine Ruf, Romana Gugenberger, Astrid Hagelkrüys, Núria Montserrat, I. Kozieradzki, Omar Hasan Ali, Johannes Stadlmann, Michael R. Holbrook, Connie S. Schmaljohn, Chris Oostenbrink, Robert H. Shoemaker, Alì Mirazimi, Gerald Wirnsberger, Josef Penninger

Bibliographic record

VenueEMBO Molecular Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of British Columbia
FundersNational Institute of Allergy and Infectious DiseasesNational Science FoundationCanadian Institutes of Health ResearchInnovative Medicines InitiativeAustrian Science FundEuropean CommissionÖsterreichischen Akademie der WissenschaftenNational Cancer InstituteEuropean Federation of Pharmaceutical Industries and AssociationsU.S. Department of Health and Human ServicesNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungCenter for Strategic Scientific Initiatives, National Cancer Institute
KeywordsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Recombinant DNAPotencyCoronavirus disease 2019 (COVID-19)VirologyAntibodyNeutralizing antibody2019-20 coronavirus outbreakChemistryMicrobiologyBiologyMolecular biologyImmunologyVirusMedicineGeneBiochemistryIn vitro

Abstract

fetched live from OpenAlex

The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.859
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.065
GPT teacher head0.409
Teacher spread0.344 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations52
Published2022
Admission routes2
Has abstractyes

Explore more

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