Short-Chain Aliphatic Polysulfonates Inhibit the Entry of <i>Plasmodium</i> into Red Blood Cells
Bibliographic record
Abstract
Several steps in the pathogenesis of a Plasmodium falciparum infection depend on interactions of parasite surface proteins with negatively charged sugars on the surface of host cells such as sialate residues or glycosaminoglycans. For these reasons, our previous studies examining agents that interfere with heparan sulfate-protein binding during amyloidogenesis suggested that short-chain aliphatic polysulfonates may prove useful as antimalarial agents. A series of related polysulfonates were synthesized and assessed both in tissue culture with the asexual stages of P. falciparum in human red blood cells and in vivo by use of Plasmodium berghei infections in mice. Poly(vinylsulfonate sodium salt) (molecular weight range, 1,500 to 3,000) proved effective in interfering with P. falciparum merozoite entry into human red blood cells and significantly delaying the increase in the level of P. berghei parasitemia in mice. The concept that anionic molecules that mimic large polysaccharide structures may have antimalarial properties has been suggested and examined previously. Our results suggest that related anionic agents [poly(vinylsulfonate sodium salt)-like molecules] orders of magnitude smaller than those previously considered may prove useful in abrogating merozoite entry into erythrocytes and may potentially block sporozoite entry into liver cells. Structure-activity studies conducted to enhance these properties may provide compounds with scope for significant further analysis and development.
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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".