Truncated ring-A amaryllidaceae alkaloid modulates the host cell integrated stress response, exhibiting antiviral activity to HSV-1 and SARSCoV-2
Bibliographic record
Abstract
The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives enabled identification of the 7-hydroxyl derivative as a potent and selective antiviral agent targeting SARSCoV-2 and HSV-1. The concentration of this small molecule that inhibited HSV-1 infection by 50% (IC50), determined by using induced pluripotent stem cells (iPCS)-derived brain organ organoids generated from two iPCS lines, was estimated to be 0.504 µM and 0.209 µM. No significant reduction in organoid viability was observed at concentrations up to 50 mM. Genomic expression analyses revealed a significant effect on host-cell innate immunity, revealing activation of the integrated stress response via PERK kinase upregulation, phosphorylation of eukaryotic initiation factor 2α (eIF2α) and type I IFN, as factors potentiating multiple host-defense mechanisms against viral infection. Following infection of mouse eyes with HSV-1, treatment with the compound dramatically reduced HSV-1 shedding in vivo.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".