{
  "abstract": "Malaria is a devastating disease that resulted in an estimated 610,000 deaths in 2024, the majority being children under the age of five. Here, we use KNX-115 to illustrate multistage antiparasitic activity upon targeting the cytoskeletal enzyme Plasmodium falciparum myosin A (PfMyoA). KNX-115 inhibits purified actin-activated ATPase with a potency in the low nanomolar range and >50-fold selectivity against cardiac, skeletal, and smooth muscle myosins. KNX-115 traps PfMyoA in a state that binds weakly to actin. A 2.35 Å resolution structure of KNX-115 bound to PfMyoA reveals critical interactions contributing to its mechanism of action. Importantly, in vitro evolution data reveal that KNX-115 engages PfMyoA as a sole cellular target. Inhibiting PfMyoA blocks the development of the blood and liver stages of laboratory strains of P. falciparum , with no liver cell toxicity, sporozoite cell traversal and motility, and sporozoite development in the mosquito. Inhibiting PfMyoA completely kills parasites after 96 h of treatment. Furthermore, KNX-115 is equally effective at inhibiting a panel of Plasmodium strains resistant to experimental and marketed antimalarials and shows inhibitory activity against P. falciparum circulating isolates from the Brazilian Amazon. Inhibiting PfMyoA with KNX-115 also blocks the blood stage of a laboratory strain of Plasmodium vivax . In line with the evolutionary identity of MyoA among various apicomplexan parasites, KNX-115 also inhibits Cryptosporidium and Eimeria MyoA in vitro and is an effective inhibitor of Cryptosporidium , Toxoplasma, and Eimeria cellular growth, with EC 50 s similar to those found for blood and liver stage Plasmodium .",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 42,
  "authors": [
    {
      "name": "Darshan Trivedi"
    },
    {
      "name": "Anastasia Karabina"
    },
    {
      "name": "Tiantian Jiang"
    },
    {
      "name": "Daisy Chen"
    },
    {
      "name": "Nimisha Mittal"
    },
    {
      "name": "Tonnie Huijs"
    },
    {
      "name": "Rianne van der Laak"
    },
    {
      "name": "Jin Jeon"
    },
    {
      "name": "Tomas Yeo"
    },
    {
      "name": "Dihia Moussaoui"
    },
    {
      "name": "James Robblee"
    },
    {
      "name": "Marianna Akey"
    },
    {
      "name": "Matthew Freese"
    },
    {
      "name": "Lorraine Fuller"
    },
    {
      "name": "Gustave Bergnes"
    },
    {
      "name": "Alice Racca"
    },
    {
      "name": "Heba Wander"
    },
    {
      "name": "Seongwon Jung"
    },
    {
      "name": "Stephanie Ouchida"
    },
    {
      "name": "Paul Ruijgrok"
    },
    {
      "name": "Dan Song"
    },
    {
      "name": "Annamma Spudich"
    },
    {
      "name": "Kathleen Ruppel"
    },
    {
      "name": "Suman Nag"
    },
    {
      "name": "Christoph Mueller-Dieckmann"
    },
    {
      "name": "Jeremy Burrows"
    },
    {
      "name": "Benoît Laleu"
    },
    {
      "name": "Rafael Victorio Carvalho Guido"
    },
    {
      "name": "Anna Caroline Campos Aguiar"
    },
    {
      "name": "Dhelio Batista Pereira"
    },
    {
      "name": "Sergio Wittlin"
    },
    {
      "name": "Partha Mukherjee"
    },
    {
      "name": "Arnish Chakraborty"
    },
    {
      "name": "Samuel Aggrey"
    },
    {
      "name": "Julien Robert-Paganin"
    },
    {
      "name": "Kathleen Trybus"
    },
    {
      "name": "L. David Sibley"
    },
    {
      "name": "Anne Houdusse"
    },
    {
      "name": "David Fidock"
    },
    {
      "name": "Koen Dechering"
    },
    {
      "name": "Elizabeth Winzeler"
    },
    {
      "name": "James Spudich"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8wc02qn26gf43.bib",
  "cited_by": 1,
  "doi": "10.1073/pnas.2608709123",
  "fulltext_url": null,
  "id": "8wc02qn26gf43",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://hal.science/hal-05765366v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "0.sdv"
    ],
    [
      "hal",
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    [
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    [
      "openalex",
      "2739|Malaria Research and Control"
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  "openalex": "W7170688720",
  "pdf_url": "https://hal.science/hal-05765366/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-24",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/8wc02qn26gf43.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "hal-05765366",
      "source": "hal",
      "url": "https://hal.science/hal-05765366v1"
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  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.bs",
      "subfield": "structural-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    }
  ],
  "title": "Antimalarial cytoskeletal targeting with broad apicomplexan activity",
  "title_text": "Antimalarial cytoskeletal targeting with broad apicomplexan activity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/8wc02qn26gf43",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}