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Record W4403896457 · doi:10.1021/acsptsci.4c00424

Amaryllidaceae Alkaloids Screen Unveils Potent Anticoronaviral Compounds and Associated Structural Determinants

2024· article· en· W4403896457 on OpenAlex
Natacha Mérindol, Luan Letieri Belem Martins, Ghada Elfayres, Alexandre Custeau, Lionel Berthoux, Antonio Evidente, Isabel Desgagné‐Penix

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
FieldChemistry
TopicChemical synthesis and alkaloids
Canadian institutionsUniversité du Québec à Trois-Rivières
FundersCanada Research Chairs
KeywordsAmaryllidaceaeAmaryllidaceae AlkaloidsLycorineChemistryTraditional medicineAlkaloidStereochemistryBiologyBotanyMedicine

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Betacoronaviruses encompass a spectrum of respiratory diseases, from common cold caused by the human coronavirus (HCoV)-OC43 to life-threatening severe acute respiratory syndrome (SARS)-CoV-2. Addressing the constant need for novel antiviral compounds, we turned to the exploration of 40 plant-specialized metabolites produced by the medicinal plant family Amaryllidaceae, known to produce lycorine, a strong antiviral alkaloid. The present screen included 35 alkaloids with representatives of 8 ring-type structures. Pancracine, crinamine, hemanthamine, and hemanthidine exhibited potency comparable to lycorine in blocking HCoV–OC43 replication, while amarbellisine demonstrated superior efficacy (SI = 60, EC 50 = 0.2 μM). Their anticoronaviral activity was confirmed using a SARS-CoV-2 replicon system. Time-of-drug-addition experiments established that a postentry step consistent with ribonucleic acid (RNA) replication or translation was targeted. Most antiviral Amaryllidaceae alkaloids selectively induced the expression of transcripts associated with the integrated stress response. Structure–activity relationship analyses elucidated key functional groups contributing to antiviral properties in the crinine- and lycorine-type. This study reveals that Amaryllidaceae produce a diverse repertoire of promising antiviral compounds in addition to lycorine, offering insights for developing new antiviral agents.

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)0.000
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 score0.134
Threshold uncertainty score0.946

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 studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.016
GPT teacher head0.303
Teacher spread0.287 · 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