Kinetic modeling and LC-MS/MS-based evaluation of naringenin in elicited Commiphora wightii (Arnott.) Bhandari callus with computational targeting against Zika virus

• First report on naringenin production from Commiphora wightii cell cultures. • Biomass and naringenin modeled via Boltzmann, DoseResp, and GaussAmp equations. • Elicitation effects on growth rate and naringenin production rate were analyzed. • Elicited cultures showed higher TPC, TFC, and antioxidant effects. • Naringenin validated as broad-spectrum Zika candidate via MD simulation. Naringenin, a bioactive flavanone with diverse therapeutic potential, can be sustainably produced through plant cell cultures, offering an alternative to the wild harvesting of endangered species. This study employed Commiphora wightii , a critically endangered medicinal plant native to western India, to develop in vitro callus cultures for enhanced naringenin production. Leaf-derived calluses were established on B5 medium with 1.5 mg/L 2,4-D, and naringenin was identified and quantified by LC-MS/MS, with biomass and metabolite kinetics modelled mathematically. Elicitation using l -phenylalanine and silver nitrate significantly improved yields, with 200 mg/L-phenylalanine producing 3.8 ± 0.31 mg/g—about 190-fold higher than control (0.02 ± 0.002 mg/g)—and the highest specific production rate (qₚ) observed at 100–200 mg/L-phenylalanine and 3 % silver nitrate. Biochemical assays revealed maximum total phenolic content (TPC) (224.54 ± 3.91 µg GAE/g DW) and total flavonoid content (TFC) (535.33 µg RE/g DW) under 50 mg/L-phenylalanine, alongside strong antioxidant activity (lowest IC₅₀ of 1.46 ng/mL at day 21 and 1.14 ng/mL at day 28). Multivariate analyses (heatmap, PLS-DA) confirmed elicitation effects on metabolite profiles. Molecular docking and dynamics simulations demonstrated stable, high-affinity binding of naringenin to Zika virus proteins—Envelope (5JHM), NS3 helicase (5JRZ), and NS5 polymerase (6LD5)—with RMSD values <10 Å and consistent amino acid interactions, suggesting broad-spectrum antiviral potential. These results establish C. wightii callus cultures as a conservation-oriented, high-yield platform for naringenin biosynthesis with promising antiviral applications.