{
  "abstract": "Malaria caused by Plasmodium falciparum remains a major health threat, killing over 600,000 people annually. The spread of resistance to all major antimalarials, including artemisinins, highlights the urgent need for new drugs with distinct mechanisms of action. Here, we show that the G-quadruplex ligand RHPS4, an acridine derivative, displays strong antiplasmodial activity against both drug-sensitive and drug-resistant P. falciparum strains and clinical isolates. RHPS4 primarily targets the trophozoite stage and induces major mitochondrial alterations, including reduction of mitochondrial DNA (mtDNA) and transcriptional dysfunctions. Bioinformatic analyses identified at least eight putative G4-forming sequences within the parasite’s mtDNA. Biophysical studies confirmed G4 folding of at least one sequence and its interaction with RHPS4. These findings indicate that RHPS4 impacts P. falciparum mitochondrial DNA replication and transcription, leading to parasite death, and establish G4 ligands as novel antimalarial agents.",
  "abstract_shown": true,
  "affiliations": [
    "IPBS, CNRS, Université de Toulouse, Toulouse, France",
    "Université de Toulouse, CNRS, Inserm, LCC, ERL 1289 MAAP, Toulouse, France",
    "Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, Palaiseau, France",
    "CNRS UMR9187, INSERM U1196, Institut Curie, PSL Research University, Orsay, France",
    "Université Paris-Saclay, CEA, CNRS - Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mariam Salim"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lucie Paloque",
      "orcid": "0000-0003-0359-3959"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Flore Nardella",
      "orcid": "0000-0002-3811-1633"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thibaud Reyser"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Michel Nguyen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jean-Michel Augereau"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yu Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Sébastien Britton",
      "orcid": "0000-0002-7008-5316"
    },
    {
      "affs": [
        2
      ],
      "name": "Jean-Louis Mergny"
    },
    {
      "affs": [
        4
      ],
      "name": "Virginie Gervais"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Françoise Benoit-Vical",
      "orcid": "0000-0002-9468-4823"
    },
    {
      "affs": [
        0
      ],
      "name": "Dennis Gomez",
      "orcid": "0000-0001-9942-1451"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1xc3pp2h3rzjv.bib",
  "cited_by": 0,
  "doi": "10.1128/aac.00144-26",
  "fulltext_url": "https://journals.asm.org/doi/10.1128/aac.00144-26",
  "id": "1xc3pp2h3rzjv",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://hal.science/hal-05802361v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "heading",
      "Experimental Therapeutics"
    ],
    [
      "lcc",
      "QR1-502"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
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  "openalex": "W7215065335",
  "pdf_url": null,
  "pmcid": "PMC13731234",
  "pmid": "42820840",
  "published": "2026-10-01",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/1xc3pp2h3rzjv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "hal-05802361",
      "source": "hal",
      "url": "https://hal.science/hal-05802361v1"
    },
    {
      "first_seen": "2026-11-04T14:20:44Z",
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      "url": "https://doi.org/10.1128/aac.00144-26"
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    {
      "first_seen": "2026-11-08T12:21:28Z",
      "native_id": "PMC13731234",
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    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "G-quadruplex-binding ligand RHPS4 reduces Plasmodium falciparum mitochondrial DNA level providing a novel antimalarial strategy",
  "title_text": "G-quadruplex-binding ligand RHPS4 reduces Plasmodium falciparum mitochondrial DNA level providing a novel antimalarial strategy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:28Z",
  "url": "https://research.draconitic.com/paper/1xc3pp2h3rzjv",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}