ArticleNature communications2024
Targeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Sulfonium-Based Antimicrobial Block Copolymers: Influence of Hydrophobicity on Biological Activity and Antibiotic Synergy.Macromolecular rapid communications · 2026Article
- A pneumolysin mutant (ΔA146 ply) induces pyroptosis in triple-negative and HER2-positive breast cancer cells via the Caspase-1/GSDME pathway: a potential antibody-drug conjugate payload.Translational cancer research · 2026Article
- Orally available designed miniproteins inhibit enterotoxigenicbioRxiv : the preprint server for biology · 2026Article
- Evaluation of molecular interactions of vaping juice components with ACE2 receptor.Scientific reports · 2026Article
- Pneumolysin-responsive liposomal platform for selective treatment of Streptococcus pneumoniae.Drug delivery and translational research · 2025Article
- Streptococcus pneumoniae epidemiology, pathogenesis and control.Nature reviews. Microbiology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Pneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pneumoniae, the main cause for bacterial pneumonia. Liberation of PLY during infection leads to compromised immune system and cytolytic cell death. Here, we report discovery, development, and validation of targeted small molecule inhibitors of PLY (pore-blockers, PB). PB-1 is a virtual screening hit inhibiting PLY-mediated hemolysis. Structural optimization provides PB-2 with improved efficacy. Cryo-electron tomography reveals that PB-2 blocks PLY-binding to cholesterol-containing membranes and subsequent pore formation. Scaffold-hopping delivers PB-3 with superior chemical stability and solubility. PB-3, formed in a protein-templated reaction, binds to Cys428 adjacent to the cholesterol recognition domain of PLY with a K
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.