{
  "abstract": "Can target breadth and mutation resilience be evaluated as distinct, complementary properties when prioritizing antimalarial chemotypes from African natural-product-inspired chemical space? We addressed this question by linking chemical-space expansion to target-specific docking and a per-target resistance-resilience score (RRS), while keeping computational evidence separate from biological activity. A hybrid library of 65 856 molecules, generated from 396 African natural products and 454 synthetic antimalarial compounds, yielded 19 913 computationally prioritized synthesizable leads. A 17-member polypharmacology-oriented cohort was evaluated by AutoDock Vina against PfDHFR, PfCRT, PfClpP, and PfATP4 using target-specific structural anchors. All 68 candidate–target pairs passed the geometric pose-quality criterion, with scores ranging from −7.91 kcal/mol to −4.63 kcal/mol. Per-target RRS was calculated from separate PfDHFR (N51I, C59R, S108N, I164L) and PfCRT (K76T, K76A) mutant panels, excluding non-binding wild-type targets from the denominator. The cohort comprised six A*, five B, five C, and one D RRS profiles, spanning 68.2 to 111.7. Cross-metric associations were weak or non-significant after multiplicity correction: PNS–RRS ρ = −0.559, ACSI–RRS ρ = −0.132, and RRS–wild-type score ρ = −0.433. The resulting target profiles define testable hypotheses about chemotype breadth and mutation resilience; they do not establish potency, target engagement, or resistance circumvention.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physics, Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon",
    "Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue Nord, Sherbrooke, QC, Canada, J1H 5N4",
    "Faculty of Science, University of Yaoundé, P.O. Box 812, Yaoundé, Cameroon"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Myke Vital Sao Temgoua"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Pierre Tchapet Njafa"
    },
    {
      "affs": [
        1
      ],
      "name": "Penabei Samafou"
    },
    {
      "affs": [
        2
      ],
      "name": "Wilfred Fon Mbacham"
    },
    {
      "affs": [
        0
      ],
      "name": "Serge Guy Nana Engo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1a0ensybjra9d.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15006437/v2",
  "fulltext_url": null,
  "id": "1a0ensybjra9d",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15006437/v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7211924459",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15006437/v2",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/1a0ensybjra9d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15006437",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15006437/v2"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Target breadth and mutation resilience in African-natural-product-inspired antimalarial chemotypes: a computational analysis",
  "title_text": "Target breadth and mutation resilience in African-natural-product-inspired antimalarial chemotypes: a computational analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/1a0ensybjra9d",
  "venue": "ChemRxiv",
  "versions": []
}