Original Article

Antiviral activity of biogenic silver nanoparticles against HSV-1: integrating computational modeling and experimental validation

Abstract

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.

1. Sinclair TR, van den Hengel SK, Raza BG, Rutjes SA, de Roda Husman AM, Peijnenburg WJGM, et al. Surface chemistry-dependent antiviral activity of silver nanoparticles. Nanotechnology 2021; 32. doi: 10.1088/1361-6528/ac03d6.
2. Morens DM, Folkers GK, Fauci AS. The challenge of emerging and re-emerging infectious diseases. Nature 2004; 430: 242-249.
3. Luceri A, Francese R, Lembo D, Ferraris M, Balagna C. Silver Nanoparticles: Review of Antiviral Properties, Mechanism of Action and Applications. Microorganisms 2023; 11: 629.
4. Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, et al. A review: Mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol 2021; 35: 20587384211002621.
5. Zhu S, Viejo-Borbolla A. Pathogenesis and virulence of herpes simplex virus. Virulence 2021; 12: 2670-2702.
6. Sharmin S, Rahaman MM, Sarkar C, Atolani O, Islam MT, Adeyemi OS. Nanoparticles as antimicrobial and antiviral agents: A literature-based perspective study. Heliyon 2021; 7(3): e06456.
7. Liaqat N, Jahan N, Khalil-Ur-Rahman, Anwar T, Qureshi H. Green synthesized silver nanoparticles: Optimization, characterization, antimicrobial activity, and cytotoxicity study by hemolysis assay. Front Chem 2022; 10: 952006.
8. Aletayeb P, Ghadam P, Mohammadi P. Green synthesis of AgCl/Ag(3)PO(4) nanoparticle using cyanobacteria and assessment of its antibacterial, colorimetric detection of heavy metals and antioxidant properties. IET Nanobiotechnol 2020; 14: 707-713.
9. Zhao J, Wang X, Hoang SA, Bolan NS, Kirkham MB, Liu J, et al. Silver nanoparticles in aquatic sediments: Occurrence, chemical transformations, toxicity, and analytical methods. J Hazard Mater 2021; 418: 126368.
10. Abbasi Z, Feizi S, Taghipour E, Ghadam P. Green synthesis of silver nanoparticles using aqueous extract of dried Juglans regia green husk and examination of its biological properties. Green Process Synth 2017; 6: 477-485.
11. Feizi S, Taghipour E, Ghadam P, Mohammadi P. Antifungal, antibacterial, antibiofilm and colorimetric sensing of toxic metals activities of eco friendly, economical synthesized Ag/AgCl nanoparticles using Malva Sylvestris leaf extracts. Microb Pathog 2018; 125: 33-42.
12. Ayadi Hassan S, Gorji V, Ghadam P. The efficient magnetic separation of the four biogenic nanoparticles from aqueous media by the unmodified iron oxide nanoparticles. Int J Environ Sci Technol 2021; 18: 3883-3894.
13. Ahmadi M, Elikaei A, Ghadam P. Antiviral activity of biosynthesized copper nanoparticle by Juglans regia green husk aqueous extract and Iron nanoparticle: molecular docking and in-vitro studies. Iran J Microbiol 2023; 15: 138-148.
14. Bitencourt-Ferreira G, de Azevedo WF Jr. Molegro Virtual Docker for Docking. Methods Mol Biol 2019; 2053: 149-167.
15. Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking. J Med Chem 2006; 49: 3315-3321.
16. Dubey K, Dubey R. Computation screening of narcissoside a glycosyloxyflavone for potential novel coronavirus 2019 (COVID-19) inhibitor. Biomed J 2020; 43: 363-367.
17. Qiu B, Shao Q, Shi J, Yang C, Chu H. Application of biochar for the adsorption of organic pollutants from wastewater: Modification strategies, mechanisms and challenges. Sep Purif Technol 2022; 300: 121925.
18. Lei C, Yang J, Hu J, Sun X. On the calculation of TCID50 for quantitation of virus infectivity. Virol Sin 2021; 36: 141-144.
19. Ramalingam V, Rajaram R, Premkumar C, Santhanam P, Dhinesh P, Vinothkumar S, et al. Biosynthesis of silver nanoparticles from deep sea bacterium Pseudomonas aeruginosa JQ989348 for antimicrobial, antibiofilm, and cytotoxic activity. J Basic Microbiol 2014; 54: 928-936.
20. Mwilu SK, Siska E, Baig RBN, Varma RS, Heithmar E, Rogers KR. Separation and measurement of silver nanoparticles and silver ions using magnetic particles. Sci Total Environ 2014; 472: 316-323.
21. Lunardi CN, Gomes AJ, Rocha FS, De Tommaso J, Patience GS. Experimental methods in chemical engineering: Zeta potential. Can J Chem Eng 2021; 99: 627-639.
22. He Q, Lu J, Liu N, Lu W, Li Y, Shang C, et al. Antiviral Properties of Silver Nanoparticles against SARS-CoV-2: Effects of Surface Coating and Particle Size. Nanomaterials (Basel) 2022; 12: 990.
23. Liang T, Hou JR, Qu M, Xi JX, Raj I. Application of nanomaterial for enhanced oil recovery. Pet Sci 2022; 19: 882-899.
24. Park SJ, Seo MK (2011). Intermolecular Force. In: Interface Science and Composites. Elsevier, pp. 1-57.
25. Al-kawmani AA, Alanazi KM, Farah MA, Ali MA, Hailan WA, Al-Hemaid FM. Apoptosis-inducing potential of biosynthesized silver nanoparticles in breast cancer cells. J King Saud Univ Sci 2020; 32: 2480-2488.
26. Dove AS, Dzurny DI, Dees WR, Qin N, Nunez Rodriguez CC, Alt LA, et al. Silver nanoparticles enhance the efficacy of aminoglycosides against antibiotic-resistant bacteria. Front Microbiol 2023; 13: 1064095.
27. Laine RF, Albecka A, Linde S Van De, Rees EJ, Crump CM, Kaminski CF. Structural analysis of herpes simplex virus by optical super-resolution imaging. Nat Commun 2015; 6: 5980.
28. Ratan ZA, Mashrur FR, Chhoan AP, Shahriar SM, Haidere MF, Runa NJ, et al. Silver Nanoparticles as Potential Antiviral Agents. Pharmaceutics 2021; 13: 2034.
29. Salleh A, Naomi R, Utami ND, Mohammad AW, Mahmoudi E, Mustafa N, et al. The potential of silver nanoparticles for antiviral and antibacterial applications: a mechanism of action. Nanomaterials (Basel) 2020; 10: 1566.
30. Gaikwad S, Ingle A, Gade A, Rai M, Falanga A, Incoronato N, et al. Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3. Int J Nanomed 2013; 8: 4303-4314.
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IssueVol 18 No 4 (2026) QRcode
SectionOriginal Article(s)
Keywords
Antiviral agents Herpes simplex virus type 1 Metal nanoparticles Molecular docking Plant extracts

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How to Cite
1.
Soltani M, Elikaei A, Ghadam P, Ayadi Hassan S. Antiviral activity of biogenic silver nanoparticles against HSV-1: integrating computational modeling and experimental validation. Iran J Microbiol. 2026;18(4):584‑594.