ArticleProceedings of the National Academy of Sciences of the United States of America2010
Repositioning of an existing drug for the neglected tropical disease Onchocerciasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 104 citations in OpenAlex.
- Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease.Frontiers in parasitology · 2026Review
- DInternational journal of molecular sciences · 2024Article
- Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.Frontiers in pharmacology · 2024Review
- A novel efficient drug repurposing framework through drug-disease association data integration using convolutional neural networks.BMC bioinformatics · 2023Article
- Current status of usage of ivermectin in the management of COVID.Journal of advanced pharmaceutical technology & research · 2022Article
- Discovery of novel inhibitors targeting nematode chitinase CFrontiers in chemistry · 2022Article
- Structure-based virtual screening of highly potent inhibitors of the nematode chitinaseJournal of enzyme inhibition and medicinal chemistry · 2021Article
- SNF-NN: computational method to predict drug-disease interactions using similarity network fusion and neural networks.BMC bioinformatics · 2021Article
- A review of computational drug repositioning: strategies, approaches, opportunities, challenges, and directions.Journal of cheminformatics · 2020Review
- A comparative chemogenic analysis for predicting Drug-Target Pair via Machine Learning Approaches.Scientific reports · 2020Article
- Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 1. Amide Linked Analogs.ACS infectious diseases · 2020Article
- Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 2. Ketone Linked Analogs.ACS infectious diseases · 2020Article
- 1,1-Diaryl compounds as important bioactive module in pesticides.Molecular diversity · 2019Review
- Structural dissection reveals a general mechanistic principle for group II chitinase (ChtII) inhibition.The Journal of biological chemistry · 2019Article
- Development of a preliminary in vitro drug screening assay based on a newly established culturing system for pre-adult fifth-stage Onchocerca volvulus worms.PLoS neglected tropical diseases · 2019Article
- Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.Infectious diseases of poverty · 2018Article
- Alternative treatment strategies to accelerate the elimination of onchocerciasis.International health · 2018Article
- The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug.American journal of cancer research · 2018Review
- Mining Filarial Genomes for Diagnostic and Therapeutic Targets.Trends in parasitology · 2018Review
- Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus that affects more than 37 million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from O. volvulus was recently discovered, however, its exact role in the worm's metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, closantel was found also to completely inhibit molting of O. volvulus infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel closantel's effects, a retro-fragment-based study was used to define structural elements critical for closantel's chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against O. volvulus provides promise in the hunt for new therapies against river blindness.
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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.