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Record W4404068475 · doi:10.1021/acsptsci.4c00512

Repurposing Drugs and Synergistic Combinations as Potential Therapies for Inhibiting SARS-CoV-2 and Coronavirus Replication

2024· article· en· W4404068475 on OpenAlex
Richard Boulon, Clément Mazeaud, Majid D. Farahani, Mathilde Broquière, Mustapha Iddir, Tania Charpentier, Anaïs Anton, Yann Ayotte, Simon Woo, Alain Lamarre, Laurent Chatel‐Chaix, Steven R. LaPlante

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

VenueACS Pharmacology & Translational Science · 2024
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsInstitut National de la Recherche Scientifique
FundersFonds de Recherche du Québec - SantéMitacsQuébec Consortium for Drug DiscoveryInstitut PasteurInstitut national de la recherche scientifiqueArmand-Frappier Foundation
KeywordsDrug repositioningRepurposingCoronavirusSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Computational biologyDrugApproved drugBetacoronavirusCoronavirus disease 2019 (COVID-19)PandemicFavipiravirBiologyDrug discoveryNelfinavir2019-20 coronavirus outbreakVirologyMedicinePharmacologyBioinformaticsVirusViral loadInfectious disease (medical specialty)Disease

Abstract

fetched live from OpenAlex

Drug repurposing can serve an important role in rapidly discovering medicament options for emerging microbial pandemics. In this study, a pragmatic approach is demonstrated for screening and testing drug combinations as potential broad-spectrum therapies against SARS-CoV-2 and other betacoronaviruses. Rapid cell-based phenotypic small molecule screens were executed using related common-cold-causing HCoV-OC43 betacoronavirus to identify replication inhibitors from a library of drugs approved by regulatory agencies for other indications. Given the best inhibitors, an expedient checkerboard strategy then served to identify synergistic drug combinations. These combinations were then validated using more challenging assays involving SARS-CoV-2 and variants. Promising drug combinations against multiple viral variants were discovered and involved Tilorone with Nelfinavir or Molnupiravir.

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: Empirical
Teacher disagreement score0.038
Threshold uncertainty score0.412

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
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 head0.058
GPT teacher head0.428
Teacher spread0.370 · 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