Failed Repurposing of Lysosomotropic Drugs for COVID-19 Treatment or Prevention
Bibliographic record
Abstract
The hope for the rapid discovery of an effective drug therapy for COVID-19 has led to several efforts to repurpose drugs approved for other indications. Lysosomotropic drugs, organic amines such as chloroquine, hydroxychloroquine, amiodarone and many others, were found to interfere with the viral life cycle in vitro but have failed in clinical trials. The properties of lysosomotropic drugs and the vacuolar cytopathology induced by them are briefly reviewed, including the critical role of lipophilicity, the central role of vacuolar (V)-ATPase for their concentration in acidic organelles, the altered function of these organelles including impaired endocytosis and secretion, macroautophagic accumulation and secondary phospholipidosis. The apparent preferential uptake of lysosomotropic drugs by phagocytic leukocytes (macrophages, neutrophils) and the high concentrations needed for a sustained disruption of vacuolar trafficking may have contributed to the failure of lysosomotropic drug repurposing for COVID-19.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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".