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A new class of natural anthelmintics targeting lipid metabolism

Author

Listed:
  • Hala Zahreddine Fahs

    (New York University Abu Dhabi
    New York University)

  • Fathima S. Refai

    (New York University Abu Dhabi)

  • Suma Gopinadhan

    (New York University Abu Dhabi)

  • Yasmine Moussa

    (New York University Abu Dhabi)

  • Hin Hark Gan

    (New York University)

  • Yamanappa Hunashal

    (New York University Abu Dhabi)

  • Gennaro Battaglia

    (New York University Abu Dhabi
    Università di Napoli “Federico II”)

  • Patricia G. Cipriani

    (New York University Abu Dhabi
    New York University)

  • Claire Ciancia

    (University of Glasgow)

  • Nabil Rahiman

    (New York University Abu Dhabi)

  • Stephan Kremb

    (New York University Abu Dhabi)

  • Xin Xie

    (New York University Abu Dhabi)

  • Yanthe E. Pearson

    (New York University Abu Dhabi)

  • Glenn L. Butterfoss

    (New York University Abu Dhabi)

  • Rick M. Maizels

    (University of Glasgow)

  • Gennaro Esposito

    (New York University Abu Dhabi
    Istituto Nazionale Biostrutture e Biosistemi)

  • Antony P. Page

    (University of Glasgow)

  • Kristin C. Gunsalus

    (New York University Abu Dhabi
    New York University)

  • Fabio Piano

    (New York University Abu Dhabi
    New York University)

Abstract

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.

Suggested Citation

  • Hala Zahreddine Fahs & Fathima S. Refai & Suma Gopinadhan & Yasmine Moussa & Hin Hark Gan & Yamanappa Hunashal & Gennaro Battaglia & Patricia G. Cipriani & Claire Ciancia & Nabil Rahiman & Stephan Kre, 2025. "A new class of natural anthelmintics targeting lipid metabolism," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54965-w
    DOI: 10.1038/s41467-024-54965-w
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    References listed on IDEAS

    as
    1. Tamar Hashimshony & Martin Feder & Michal Levin & Brian K. Hall & Itai Yanai, 2015. "Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer," Nature, Nature, vol. 519(7542), pages 219-222, March.
    2. Andrew R. Burns & Genna M. Luciani & Gabriel Musso & Rachel Bagg & May Yeo & Yuqian Zhang & Luckshika Rajendran & John Glavin & Robert Hunter & Elizabeth Redman & Susan Stasiuk & Michael Schertzberg &, 2015. "Caenorhabditis elegans is a useful model for anthelmintic discovery," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    3. Jia Wei & Liang Tong, 2015. "Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer," Nature, Nature, vol. 526(7575), pages 723-727, October.
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