ArticleAntimicrobial agents and chemotherapy2015
The Glucose Transporter PfHT1 Is an Antimalarial Target of the HIV Protease Inhibitor Lopinavir.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Trial
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- An overview of the Plasmodium falciparum hexose transporter and its therapeutic interventions.Proteins · 2022Review
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- Effect of HIV aspartyl protease inhibitors on experimental infection with a cystogenic Me49 strain ofPathogens and global health · 2022Article
- Transporter-Mediated Solutes Uptake as Drug Target inFrontiers in pharmacology · 2022Review
- Potent Synergistic Interactions between Lopinavir and Azole Antifungal Drugs against Emerging Multidrug-Resistant Candida auris.Antimicrobial agents and chemotherapy · 2020Article
- Malaria parasite plasmepsins: More than just plain old degradative pepsins.The Journal of biological chemistry · 2020Review
- Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery.Infection and drug resistance · 2020Review
- Article
- Buy one, get one free? Benefits of certain antiretrovirals against malaria.AIDS (London, England) · 2017Article
- Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases.Pharmacology research & perspectives · 2017Review
- SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy.Scientific reports · 2016Article
- A Novel Fluorescence Resonance Energy Transfer-Based Screen in High-Throughput Format To Identify Inhibitors of Malarial and Human Glucose Transporters.Antimicrobial agents and chemotherapy · 2016Article
- Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis.Science signaling · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Malaria and HIV infection are coendemic in a large portion of the world and remain a major cause of morbidity and mortality. Growing resistance of Plasmodium species to existing therapies has increased the need for new therapeutic approaches. The Plasmodium glucose transporter PfHT is known to be essential for parasite growth and survival. We have previously shown that HIV protease inhibitors (PIs) act as antagonists of mammalian glucose transporters. While the PI lopinavir is known to have antimalarial activity, the mechanism of action is unknown. We report here that lopinavir blocks glucose uptake into isolated malaria parasites at therapeutically relevant drug levels. Malaria parasites depend on a constant supply of glucose as their primary source of energy, and decreasing the available concentration of glucose leads to parasite death. We identified the malarial glucose transporter PfHT as a target for inhibition by lopinavir that leads to parasite death. This discovery provides a mechanistic basis for the antimalarial effect of lopinavir and provides a direct target for novel drug design with utility beyond the HIV-infected population.
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