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Record W3009970748 · doi:10.1002/minf.202000028

Rapid Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease by Deep Docking of 1.3 Billion Compounds

2020· article· en· W3009970748 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueMolecular Informatics · 2020
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsUniversity of British Columbia
FundersNational Institute on Deafness and Other Communication DisordersCanadian Institutes of Health Research
KeywordsDocking (animal)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Virtual screeningCoronavirus disease 2019 (COVID-19)Drug discoveryProteaseCoronavirusComputational biologyDrug development2019-20 coronavirus outbreakDrugComputer scienceVirologyInfectious disease (medical specialty)MedicineChemistryOutbreakBiologyBioinformaticsPharmacologyDiseaseBiochemistryEnzyme

Abstract

fetched live from OpenAlex

The recently emerged 2019 Novel Coronavirus (SARS-CoV-2) and associated COVID-19 disease cause serious or even fatal respiratory tract infection and yet no approved therapeutics or effective treatment is currently available to effectively combat the outbreak. This urgent situation is pressing the world to respond with the development of novel vaccine or a small molecule therapeutics for SARS-CoV-2. Along these efforts, the structure of SARS-CoV-2 main protease (Mpro) has been rapidly resolved and made publicly available to facilitate global efforts to develop novel drug candidates. Recently, our group has developed a novel deep learning platform - Deep Docking (DD) which provides fast prediction of docking scores of Glide (or any other docking program) and, hence, enables structure-based virtual screening of billions of purchasable molecules in a short time. In the current study we applied DD to all 1.3 billion compounds from ZINC15 library to identify top 1,000 potential ligands for SARS-CoV-2 Mpro protein. The compounds are made publicly available for further characterization and development by scientific community.

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.

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)0.000
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: none
Teacher disagreement score0.576
Threshold uncertainty score0.534

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
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 head0.018
GPT teacher head0.268
Teacher spread0.250 · 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