ArticleNature communications2022
Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed.
- Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site.Cell reports · 2026Article
- PfApiAT2 is a proline transporter essential for the transmission of Plasmodium falciparum by the mosquito vector.Nature communications · 2026Article
- Structure-Guided Optimization of Novel Inhibitors ofJournal of medicinal chemistry · 2026Article
- Discovery of a triple-site inhibitor targeting bacterial methionyl-tRNA synthetase through combined drug repurposing screening and generative AI-assisted optimization.Nucleic acids research · 2026Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- PfApiAT2 is a proline transporter essential for the transmission ofResearch square · 2026Article
- PfApiAT2 is a proline transporter essential for the transmission ofbioRxiv : the preprint server for biology · 2026Article
- Shared Binding Site but Divergent Resistance Profiles Uncover Novel Resistance Mechanisms inbioRxiv : the preprint server for biology · 2025Article
- Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.Cell chemical biology · 2025Article
- A review of natural products as a source of next-generation drugs against apicomplexan parasites.npj antimicrobials and resistance · 2025Review
- Halofuginone Disrupted Collagen Deposition via mTOR-eIF2α-ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Systematic in vitro evolution inScience (New York, N.Y.) · 2024Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- Adaptation of a eukaryote-like ProRS to a prokaryote-like tRNAPro.Nucleic acids research · 2024Article
- Adaptive evolution: Eukaryotic enzyme's specificity shift to a bacterial substrate.Protein science : a publication of the Protein Society · 2024Article
- Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.Cell chemical biology · 2024Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Article
- Transcriptome profile of halofuginone resistant and sensitive strains ofFrontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
The development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one of the world's most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged as attractive targets for malaria chemotherapy. We describe the development of a single-step biochemical assay for Plasmodium and human prolyl-tRNA synthetases that overcomes critical limitations of existing technologies and enables quantitative inhibitor profiling with high sensitivity and flexibility. Supported by this assay platform and co-crystal structures of representative inhibitor-target complexes, we develop a set of high-affinity prolyl-tRNA synthetase inhibitors, including previously elusive aminoacyl-tRNA synthetase triple-site ligands that simultaneously engage all three substrate-binding pockets. Several compounds exhibit potent dual-stage activity against Plasmodium parasites and display good cellular host selectivity. Our data inform the inhibitor requirements to overcome existing resistance mechanisms and establish a path for rational development of prolyl-tRNA synthetase-targeted anti-malarial therapies.
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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.