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Record W4283124474 · doi:10.1021/acschembio.2c00378

Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses

2022· article· en· W4283124474 on OpenAlexafffund
Xuan Yang, Rebekah J. Dickmander, Armin Bayati, Sharon Taft-Benz, Jeffery L. Smith, Carrow I. Wells, Emily A. Madden, Jason W. Brown, Erik M. Lenarcic, Boyd L. Yount, Edcon Chang, Alison D. Axtman, Ralph S. Baric, Mark T. Heise, Peter S. McPherson, Nathaniel J. Moorman, Timothy M. Willson

Bibliographic record

VenueACS Chemical Biology · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcGill UniversityStructural Genomics ConsortiumMontreal Neurological Institute and Hospital
FundersNational Institutes of HealthNatural Sciences and Engineering Research Council of CanadaFonds de recherche du QuébecParkinson Society CanadaNorth Carolina General AssemblyTakeda Pharmaceutical CompanyNorth Carolina Biotechnology CenterGraduate School, University of North Carolina at Chapel HillNational Institute of Diabetes and Digestive and Kidney DiseasesU.S. Department of Defense
KeywordsCoronavirusBiologyVirologyViral entryGene knockdownViral replicationEndocytosisKinaseCell biologyCell cultureCoronavirus disease 2019 (COVID-19)CellVirusGeneticsInfectious disease (medical specialty)

Abstract

fetched live from OpenAlex

Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human, bat, and murine β-coronaviruses. The potency of in-cell CSNK2A target engagement across the set of inhibitors correlated with antiviral activity and genetic knockdown confirmed the essential role of the CSNK2 holoenzyme in β-coronavirus replication. Spike protein endocytosis was blocked by CSNK2A inhibition, indicating that antiviral activity was due in part to a suppression of viral entry. CSNK2A inhibition may be a viable target for the development of anti-SARS-like β-coronavirus drugs.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.178
Threshold uncertainty score0.474

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.047
GPT teacher head0.349
Teacher spread0.303 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations27
Published2022
Admission routes2
Has abstractyes

Explore more

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