Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 18 4 2026 08 04 Antiviral activity of biogenic silver nanoparticles against HSV-1: integrating computational modeling and experimental validation 5244 5244 EN Mahsa Soltani Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran Ameneh Elikaei Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran Parinaz Ghadam Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran Sona Ayadi Hassan Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran 2025 01 10 2026 06 13 Background and Objectives: This study aimed to investigate the effects of biogenic silver nanoparticles (AgNPs) on Herpes simplex virus type 1 (HSV-1), focusing on the influence of plant-derived capping agents and their metal cores on antiviral efficacy and mechanism of action. Materials and Methods: Biosynthesized AgNPs using aqueous extracts of Juglans regia (J. regia) and Malva sylvestris (M. sylvestris) were characterized, and their zeta potential was assessed. Molecular docking studies were performed to illuminate the interaction between AgNPs and viral particles. The antiviral activity was evaluated using viral titer quantification and a cytotoxicity assay, both performed on Vero cells. Results: AgNPs exhibited zeta potentials of -8.87 mV and -5.49 mV for J. regia and M. sylvestris, respectively, indicating their stability and potential for interaction with viral particles. Strong binding affinities between AgNPs and viral glycoprotein D (gD) were revealed by molecular docking, which obtained negative MolDock scores. The antiviral assays demonstrated a ten-thousand-fold reduction in viral titers. Conclusion: This research underscores the critical roles of capping agents and the metallic core in modulating the antiviral efficacy of plant-derived AgNPs against HSV‑1, establishing them as a promising platform for novel antiviral therapeutics. https://ijm.tums.ac.ir/index.php/ijm/article/view/5244 https://ijm.tums.ac.ir/index.php/ijm/article/download/5244/1918