{
  "abstract": "Calcium signaling is essential for the survival of Plasmodium falciparum, yet few components of its Ca2+ regulatory machinery have been chemically validated as antimalarial drug targets. Here, we report the structure-guided identification of small molecule inhibitors targeting a parasite specific subset of calmodulin and calmodulin-like proteins that lack close human orthologs. Virtual screening followed by biophysical validation revealed that the drugs Econazole, Carvedilol, and Deschloro-Lapatinib selectively engage three parasite calmodulin paralogs (PfCam200, PfCam300, and PfCam400) and inhibit their Ca2+-binding activity. Direct binding was confirmed by bio-layer interferometry and calcium-binding assays, demonstrating micromolar affinities and functional inhibition. Chemical perturbation of parasite calmodulins disrupts food vacuole directed Ca2+ trafficking, induces redistribution of intracellular Ca2+, and results in stage specific arrest of parasite development. Confocal imaging localizes PfCam200, PfCam300, and PfCam400 in proximity to the digestive vacuole transporters PfCRT and PfMDR1, supporting a mechanistic link between calmodulin function and vacuolar Ca2+ homeostasis. Collectively, these findings establish parasite calmodulins as chemically tractable targets and demonstrate the utility of repurposed small molecules as probes to interrogate essential Ca2+-dependent pathways in malaria parasites.",
  "abstract_shown": true,
  "affiliations": [
    "Malaria Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India",
    "Department of Biochemistry and Microbiology, Faculty of Pharmacy, Homs University, Syria",
    "Translational Bioinformatic Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India",
    "Parasite Cell Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India",
    "Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alma Tammour"
    },
    {
      "affs": [
        0
      ],
      "name": "Sadaf Parveen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ashutosh Panda"
    },
    {
      "affs": [
        2
      ],
      "name": "Shahnawaz Ahmad"
    },
    {
      "affs": [
        3
      ],
      "name": "Madiha Abbas"
    },
    {
      "affs": [
        4
      ],
      "name": "Hari Madhav"
    },
    {
      "affs": [
        3
      ],
      "name": "Zainab Khan"
    },
    {
      "affs": [
        0
      ],
      "name": "Anisha Thalor"
    },
    {
      "affs": [
        3
      ],
      "name": "Pragyan Parimita Rath"
    },
    {
      "affs": [
        3
      ],
      "name": "Neha Prakash"
    },
    {
      "affs": [
        0
      ],
      "name": "Iqbal Taily Junaid"
    },
    {
      "affs": [
        0
      ],
      "name": "Osama Mukhtar"
    },
    {
      "affs": [
        2
      ],
      "name": "Dinesh Gupta"
    },
    {
      "affs": [
        3
      ],
      "name": "Asif Mohmmed"
    },
    {
      "affs": [
        0
      ],
      "name": "Pawan Malhotra"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/93m5yypbqep1n.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ijpddr.2026.100673",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13717103/",
  "id": "93m5yypbqep1n",
  "issns": [
    "2211-3207"
  ],
  "landing_url": "https://doi.org/10.1016/j.ijpddr.2026.100673",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7222845917",
  "pdf_url": null,
  "pmcid": "PMC13717103",
  "pmid": "42900969",
  "published": "2026-10-17",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/93m5yypbqep1n.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:21:29Z",
      "native_id": "PMC13717103",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ijpddr.2026.100673"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Repurposed small-molecule inhibitors of Plasmodium falciparum calmodulins disrupt calcium homeostasis",
  "title_text": "Repurposed small-molecule inhibitors of Plasmodium falciparum calmodulins disrupt calcium homeostasis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:29Z",
  "url": "https://research.draconitic.com/paper/93m5yypbqep1n",
  "venue": "International Journal for Parasitology: Drugs and Drug Resistance",
  "versions": []
}