{
  "abstract": "Plant-derived flavonoids show measurable anti-dengue activity in cell culture, but their translational value is limited by a narrow therapeutic window: the concentrations that inhibit the virus approach or exceed those that are cytotoxic. Whether nanoparticle formulation can resolve this constraint, rather than simply add potency, remains untested for a chemically defined fraction. Here we show that biogenic silver nanoparticle (AgNP) formation using a flavonoid-enriched fraction of Carica papaya inverts an unusable selectivity profile into a viable one. The unformulated fraction was cytotoxic below the concentrations required for antiviral activity: its 50% cytotoxic concentration (CC50 = 134.9 ug/mL) lay below its 50% effective concentration against dengue virus serotype 2 (DENV-2; EC50 = 254.4 ug/mL), giving a Selectivity Index (SI) of 0.53. Using the same flavonoids as sole reducing and capping agents produced AgNPs (Z-average 128.4 nm; PDI 0.232; zeta potential -28.4 mV) that moved both parameters simultaneously. CC50 rose approximately 8.6-fold to 1,165.74 ug/mL while EC50 fell approximately 8.8-fold to 29.05 ug/mL, raising the SI to 40.12, an approximately 75-fold shift. Time-of-addition analysis localised the effect to the extracellular phase: inhibition was significant under pre-treatment and co-treatment but not after viral adsorption, identifying the AgNPs as entry inhibitors rather than replication inhibitors. Consistent with a serotype-independent physical mechanism, AgNP treatment at 30 ug/mL reduced viral RNA across all four serotypes, using inocula standardised against WHO-traceable NAAT reference reagents. These findings identify capping chemistry, rather than silver content alone, as a determinant of the therapeutic window in phytosynthesised nanoantivirals.",
  "abstract_shown": true,
  "affiliations": [
    "National Centre for Biological Sciences (NCBS), Centre for Cellular and Molecular Platforms (C-CAMP), Bangalore - 560065"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "M. K. Dhandapani"
    },
    {
      "name": "R. R. Bharath"
    },
    {
      "name": "G. Palanisamy"
    },
    {
      "name": "G. D. Venkatasubbu"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Bhatt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/chmkv1x6595r7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.26.754612",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1.full",
  "id": "chmkv1x6595r7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2707|Papaya Research and Applications"
    ]
  ],
  "openalex": "W7214983777",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/chmkv1x6595r7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:24Z",
      "native_id": "10.64898/2026.09.26.754612",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor",
  "title_text": "Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:24Z",
  "url": "https://research.draconitic.com/paper/chmkv1x6595r7",
  "venue": "bioRxiv",
  "versions": []
}