Superiority of Chrysophyllum oliviforme in the green synthesis of highly stable ZnO nanoparticles: metabolomic profiling, quadruple antiviral screening, and comparative MD simulations

This study presents a comprehensive comparative evaluation of the green synthesis of zinc oxide nanoparticles (ZnO NPs) using alcoholic leaf extracts from Chrysophyllum oliviforme and Chrysophyllum cainito, focusing on their phytochemical-mediated stabilization and broad-spectrum antiviral efficacy. Ultra-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (LC-ESI-TOF-MS) was employed for metabolomic fingerprinting, identifying a total of 86 bioactive metabolites. The profiling revealed that C. oliviforme possesses a significantly more robust chemical matrix, characterized by higher relative concentrations of potent antioxidant and antiviral markers, specifically chlorogenic acid (11.43%), quercetin (7.62%), and resveratrol (3.81%), compared to C. cainito. The biogenic ZnO NPs were synthesized via a sustainable bottom-up approach, where the identified polyphenolic constituents acted as both reducing and capping agents. Characterization using TEM and SEM imaging, XRD confirmed the formation of crystalline hexagonal structures. Notably, C. oliviforme-derived NPs demonstrated superior colloidal stability, evidenced by moderate absolute zeta potential, which correlates with the dense phenolic capping observed in the FTIR spectra. Biological screening against a panel of four diverse viruses, Herpes Simplex Virus type 2 (HSV-2), Human Immunodeficiency Virus type 1 (HIV-1), Avian Influenza (H5N1), and Human Adenovirus-40 (HAdV-40) revealed potent inhibitory activities. The C. oliviforme ZnO NPs exhibited the highest therapeutic potential, yielding selectivity indices (SI) of 5.17, 4.44, 8.02, and 4.09, respectively. The MD trajectories (RMSD, RMSF, and Rg) confirmed that these complexes remain stable and compact under physiological conditions. These findings underscore the superiority of C. oliviforme as a bio-template for synthesizing highly stable, multi-target antiviral nano-therapeutics.