ArticleNature communications2018
Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 3 of them syntheses that pooled it.
What it found
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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
163 citing papers in PubMed, 3 syntheses or guidelines pooled it, 300 citations in OpenAlex.
- Ubiquitin-proteasome system inFrontiers in medicine · 2024Pooled it
- Efficacy and safety of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia: a systematic review and meta-analysis.Malaria journal · 2021Pooled it
- Metabolites from Marine Sponges and Their Potential to Treat Malarial Protozoan Parasites Infection: A Systematic Review.Marine drugs · 2021Pooled it
- Pharmacokinetics and Pharmacodynamics of Antimalarial Agents: Optimizing Combination Therapies to Overcome Resistance Mechanisms.Journal of clinical pharmacology · 2026Review
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site.Cell reports · 2026Article
- Characterisation of the thermal and non-thermal stress conditions that activate the Plasmodium falciparum AP2-HS-dependent heat-shock response.PLoS pathogens · 2026Article
- Artemisinin derivative SM934 targets α-enolase to inhibit PEP-mediated TAK1 stabilization and inflammation.Science China. Life sciences · 2026Article
- A role for the poly-asparagine repeat in the Plasmodium histone acetyltransferase, PfGCN5.Nature communications · 2026Article
- Potent reaction hijacking inhibitors ofbioRxiv : the preprint server for biology · 2026Article
- Why are iron chelators not as effective as artemisinin in killing malaria parasites?Parasites & vectors · 2026Article
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- Polypharmacology in malaria treatment: single drugs, multiple mechanisms, greater impact.Trends in parasitology · 2026Review
- Article
- Integrative genomics ofbioRxiv : the preprint server for biology · 2026Article
- Heme as activator and target for artemisinin: Towards multiple pharmacological bioactivity.Biochemistry and biophysics reports · 2026Review
- Profiling 26S Proteasome Activity ofInternational journal of molecular sciences · 2026Article
- Characterization of the Regulatory AAA-ATPase Subunit Rpt3 inInternational journal of molecular sciences · 2025Article
- Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy.International journal of pharmaceutics: X · 2025Article
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Artemisinin and its derivatives (collectively referred to as ARTs) rapidly reduce the parasite burden in Plasmodium falciparum infections, and antimalarial control is highly dependent on ART combination therapies (ACTs). Decreased sensitivity to ARTs is emerging, making it critically important to understand the mechanism of action of ARTs. Here we demonstrate that dihydroartemisinin (DHA), the clinically relevant ART, kills parasites via a two-pronged mechanism, causing protein damage, and compromising parasite proteasome function. The consequent accumulation of proteasome substrates, i.e., unfolded/damaged and polyubiquitinated proteins, activates the ER stress response and underpins DHA-mediated killing. Specific inhibitors of the proteasome cause a similar build-up of polyubiquitinated proteins, leading to parasite killing. Blocking protein synthesis with a translation inhibitor or inhibiting the ubiquitin-activating enzyme, E1, reduces the level of damaged, polyubiquitinated proteins, alleviates the stress response, and dramatically antagonizes DHA activity.
Identifiers
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.