Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor
- 1National Centre for Biological Sciences (NCBS), Centre for Cellular and Molecular Platforms (C-CAMP), Bangalore - 560065
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.
Related
- Structural and Kinetic Basis for Selective Inhibition of Canine Myeloperoxidase by Staphylococcal Peroxidase Inhibitor (SPIN) Orthologs
- A CD4-CD8 T-cell circuit converts cardiac inflammation into tissue injury
- Staged maturation converts a probasal body template complex into a nucleation-competent basal plate
- Split-gas biogenic methane accounting: policy design, transparency, and international coordination.
- Assessment of Microbial Consortia for Biogenic Mineralization Potential of Lead (Pb) using Microbiologically Induced Calcite Precipitation and Nitrate Reduction
BibTeX
@misc{dhandapani2026biogenic,
title = {{Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor}},
author = {M. K. Dhandapani and R. R. Bharath and G. Palanisamy and G. D. Venkatasubbu and T. Bhatt},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754612},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor
AU - M. K. Dhandapani
AU - R. R. Bharath
AU - G. Palanisamy
AU - G. D. Venkatasubbu
AU - T. Bhatt
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754612
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754612v1
AB - 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.
ER -