Potent Antimalarial and Transmission‐Blocking Activities of Centanamycin, a Novel DNA‐Binding Agent
Bibliographic record
Abstract
Most treatments for malaria target the blood stage of infection in the human host, although few can also block transmission of the parasite to the mosquito. We show here that the compound centanamycin is very effective against blood-stage malarial infections in vitro and in vivo and has profound effects on sexual differentiation of the parasites in mosquitoes. After drug treatment, parasite development is arrested within the midguts of mosquitoes, failing to produce the infective forms that migrate to the salivary glands. The mechanism of parasite death is associated with modification of Plasmodium genomic DNA. We detected DNA damage in parasites isolated from mice 24 h after treatment with centanamycin, and, importantly, we also detected this DNA damage in parasites within mosquitoes that had fed on these mice 10 days earlier. This demonstrates that damage to parasite DNA during blood-stage infection persists from the vertebrate to the mosquito host and provides a novel biochemical strategy to block malaria transmission.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".