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Record W4413179939 · doi:10.1101/2025.08.08.668114

Structure-Activity Relationship Studies Towards Analogues of Pleconaril as Novel Enterovirus-D68 Capsid-Targeting Antivirals

2025· preprint· en· W4413179939 on OpenAlexaff
David L. Cousins, Ed Griffen, Jessica Stacey, Alpha A. Lee, Anton Hlavin, Yuliia Holota, Roman Khmil, Mykyta Kordubailo, Oleksii Kostinov, Dmytro Lesyk, Ivan G. Logvinenko, Mariia Lototska, В. В. Лысенко, A. Pashchenko, Mariia Pavlichenko, A. Rodnichenko, Anton Tkachenko, Brett L. Hurst, Justin G. Julander, Hong Wang, Rebecca L. Pearl, Jared Benjamin, Randy Diaz-Tapia, Randy A. Albrecht, Kris M. White

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicViral Infections and Immunology Research
Canadian institutionsDiscovery Centre
FundersNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthIcahn School of Medicine at Mount Sinai
KeywordsCapsidPoliovirusADMEEnterovirusPoliomyelitisVirologyBroad spectrumDarunavirChemistryDrugMedicineHuman immunodeficiency virus (HIV)VirusPharmacologyCombinatorial chemistryViral load

Abstract

fetched live from OpenAlex

Non-polio enteroviruses (NPEV) such as enterovirus D68 (EV-D68) that are highly infectious and associated with polio-like neurological complications have caused outbreaks, globally, in recent years. While some clinical and preclinical compounds have shown efficacy against NPEV in-vitro, liabilities that caused historical compounds such as pleconaril to fall short of FDA approval still remain. We present herein SAR and SPR studies of analogues of clinical compounds such as pleconaril and vapendavir against EV-D68 as a representative NPEV. Numerous structurally differentiated analogues with EV-D68 antiviral activity and useful ADME properties were discovered, which could serve as starting points for future EV drug discovery campaigns. Screening against a panel of enteroviruses revealed moderately broad-spectrum anti-EV activity of compound 26.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.059
GPT teacher head0.333
Teacher spread0.274 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2025
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicViral Infections and Immunology ResearchFrench-language works237,207