ArticlePloS one2014
Chemical and genetic validation of the statin drug target to treat the helminth disease, schistosomiasis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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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
33 citing papers in PubMed, 68 citations in OpenAlex.
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- Plant-Derived Terpenes as Emerging Therapeutics Against Schistosomiasis.International journal of molecular sciences · 2026Review
- Computational and experimental exploration of statin and statin-like compounds as potential treatment of schistosomiasis.PLoS neglected tropical diseases · 2025Article
- Repurposing statins for the treatment of larval cestodiases:Parasitology · 2025Article
- Multifaceted analysis of equine cystic echinococcosis: genotyping, immunopathology, and screening of repurposed drugs against E. equinus protoscolices.BMC veterinary research · 2025Article
- Statins, Allies against Antibiotic Resistance?Current medicinal chemistry · 2025Review
- Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.Frontiers in immunology · 2021Review
- A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.Communications biology · 2020Article
- Large-scale RNAi screening uncovers therapeutic targets in the parasiteScience (New York, N.Y.) · 2020Article
- Molecular and metabolomic changes in the proximal colon of pigs infected with Trichuris suis.Scientific reports · 2020Article
- Cloning and functional complementation of ten Schistosoma mansoni phosphodiesterases expressed in the mammalian host stages.PLoS neglected tropical diseases · 2020Article
- Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs.Biomolecules · 2020Review
- Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery.Parasites & vectors · 2019Article
- The Proteasome as a Drug Target in the Metazoan Pathogen,ACS infectious diseases · 2019Article
- WIPO Re:Search: Catalyzing Public-Private Partnerships to Accelerate Tropical Disease Drug Discovery and Development.Tropical medicine and infectious disease · 2019Article
- WIPO Re:Search-A Platform for Product-Centered Cross-Sector Partnerships for the Elimination of Schistosomiasis.Tropical medicine and infectious disease · 2019Article
- Bioactivity of Farnesyltransferase Inhibitors AgainstFrontiers in cellular and infection microbiology · 2019Article
- High Throughput and Computational Repurposing for Neglected Diseases.Pharmaceutical research · 2018Review
- TPT sulfonate, a single, oral dose schistosomicidal prodrug: In vivo efficacy, disposition and metabolic profiling.International journal for parasitology. Drugs and drug resistance · 2018Article
- Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni.International journal for parasitology. Drugs and drug resistance · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The mevalonate pathway is essential in eukaryotes and responsible for a diversity of fundamental synthetic activities. 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is the rate-limiting enzyme in the pathway and is targeted by the ubiquitous statin drugs to treat hypercholesterolemia. Independent reports have indicated the cidal effects of statins against the flatworm parasite, S. mansoni, and the possibility that SmHMGR is a useful drug target to develop new statin-based anti-schistosome therapies. For six commercially available statins, we demonstrate concentration- and time-dependent killing of immature (somule) and adult S. mansoni in vitro at sub-micromolar and micromolar concentrations, respectively. Cidal activity trends with statin lipophilicity whereby simvastatin and pravastatin are the most and least active, respectively. Worm death is preventable by excess mevalonate, the product of HMGR. Statin activity against somules was quantified both manually and automatically using a new, machine learning-based automated algorithm with congruent results. In addition, to chemical targeting, RNA interference (RNAi) of HMGR also kills somules in vitro and, again, lethality is blocked by excess mevalonate. Further, RNAi of HMGR of somules in vitro subsequently limits parasite survival in a mouse model of infection by up to 80%. Parasite death, either via statins or specific RNAi of HMGR, is associated with activation of apoptotic caspase activity. Together, our genetic and chemical data confirm that S. mansoni HMGR is an essential gene and the relevant target of statin drugs. We discuss our findings in context of a potential drug development program and the desired product profile for a new schistosomiasis drug.
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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.