A new class of natural anthelmintics targeting lipid metabolism

• Published in: Nature communications Vol. 16; no. 1; pp. 305 - 15
• Main Authors: Fahs, Hala Zahreddine, Refai, Fathima S., Gopinadhan, Suma, Moussa, Yasmine, Gan, Hin Hark, Hunashal, Yamanappa, Battaglia, Gennaro, Cipriani, Patricia G., Ciancia, Claire, Rahiman, Nabil, Kremb, Stephan, Xie, Xin, Pearson, Yanthe E., Butterfoss, Glenn L., Maizels, Rick M., Esposito, Gennaro, Page, Antony P., Gunsalus, Kristin C., Piano, Fabio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 101/47; 101/58; 101/6; 13; 13/89; 49; 49/47; 631/154/555; 64; 64/11; 692/699/255/1715; Acetates; Acetic acid; Acetyl-CoA Carboxylase - antagonists & inhibitors; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Alcohols; Animals; Anthelmintic agents; Anthelmintics - pharmacology; Anthelmintics - therapeutic use; Antiparasitic agents; Biochemical tests; Biosynthesis; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - metabolism; Developmental stages; Drug delivery; Drug metabolism; Drug resistance; Effectiveness; Egg shells; Embryos; Female; Global health; Health risks; Human populations; Humanities and Social Sciences; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Livestock; Mammalian cells; Metabolism; Mice; multidisciplinary; Multidrug resistance; Nematoda - drug effects; Paralysis; Penetration resistance; Public health; Reactive oxygen species; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54965-w

Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species: Brugia pahangi , Teladorsagia circumcincta and Heligmosomoides polygyrus , as well as a multidrug resistant strain (UGA) of Haemonchus contortus . AFA shows significant efficacy in H. polygyrus infected mice. In C. elegans , AFA exposure affects all developmental stages, causing paralysis, impaired mitochondrial respiration, increased reactive oxygen species production and mitochondrial damage. In embryos, AFAs penetrate the eggshell and induce rapid developmental arrest. Genetic and biochemical tests reveal that AFAs inhibit POD-2, encoding an acetyl CoA carboxylase, the rate-limiting enzyme in lipid biosynthesis. These results uncover a new anthelmintic class affecting lipid metabolism. Avocado fatty alcohols/acetates (AFAs) are effective against parasitic nematodes, including drug resistant strains, and show safety in mammalian cells. AFAs target lipid metabolism, offering the potential for new anthelmintic treatment pathways.