Silver Nanoparticles (AgNPs) as Potential Antiviral Agents: Synthesis, Biophysical Properties, Safety, Challenges and Future Directions─Update Review
Abstract
:1. Introduction
2. Synthesis
2.1. Physical Methods
2.2. Chemical Methods
2.3. Green Synthesis
3. Biophysical Properties
3.1. Shape and Crystallinity
3.2. Melting Temperature
3.3. Optical Properties
3.4. Electrical Properties
4. An Update on Antiviral AgNPs
5. Safety of AgNPs
Limitations of AgNPs
6. Challenges and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Plant Used | Characterization Methods | Size (nm) | Properties | Method | Application and Significance | Reference |
---|---|---|---|---|---|---|
Lallemantia royleana | TEM | 34.47 ± 1.6 | Spherical shape, antioxidant, antimicrobial, anti-inflammatory, cytotoxic | Green synthesis using leaf extract | Biocatalytic degradation of methylene blue and biopharmaceutical applications, with potential environmental and medical benefits from green synthesis using leaf extract. | [51] |
Kalanchoe fedtschenkoi | UV-Vis, FTIR, SEM, Zeta Potential | 39.9, 111, 42 | Antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa), antioxidant | Green synthesis using plant extracts | Strong antibacterial and antioxidant properties, with biomedical and nanotechnology applications, achieved through green synthesis using plant extracts. | [52] |
Rubus discolor | UV-Vis (λmax 456.01 nm), TEM, XRD, EDX, Zeta Potential (−44.2 mV) | 37 | Crystalline structure, high stability, antibacterial (MDR Escherichia coli, Pseudomonas aeruginosa), cytotoxic (A431, MCF7, HepG2) | Green synthesis using leaf extract, Response Surface Methodology | Effective in medical applications and antimicrobial coatings, with phenolics, tannins, and flavonoids contributing to bioactivity, synthesized through green methods and Response Surface Methodology. | [53] |
Green tea | XRD, FESEM, DLS | 50 | Quasi-spherical shape, antibacterial (Staphylococcus aureus, E. coli) | Green synthesis from recycled silver (radiographic films) | Sustainable nanoparticle production and antimicrobial coatings, utilizing recycled silver from radiographic films for eco-friendly synthesis. | [54] |
Malachra alceifolia | UV-Vis, XRD, SEM | 10–55 (avg. 28) | FCC crystalline structure, antibacterial Pseudomonas aeruginosa, Staphylococcus aureus, antioxidant (DPPH scavenging, IC50: 0.87 mg/mL) | Green synthesis using leaf extract | Biomedical, antimicrobial, and antioxidant applications, with strong activity attributed to green synthesis using leaf extract. | [55] |
Curcuma amada | Not specified | Not specified | Various potential applications | Surfactant-free, eco-friendly synthesis using rhizome essential oil | Eco-friendly synthesis using rhizome essential oil, focusing on biomedical and nanotechnology applications with a sustainable approach. | [56] |
Paullinia cupana Kunth (Guarana) | UV-Vis, DLS, Zeta Potential, MET, NTA, EDX | 39.33–126.2 | Spherical morphology, high colloidal stability, antibacterial, antioxidant, cytotoxic against cancer cells, effective against Leishmania | Green synthesis using aqueous leaf extract | Sustainable AgNP synthesis with diverse applications in biomedical, environmental, and industrial fields. Seasonal extract variation enhances properties. | [57] |
Sr.No | Method of Synthesis of AgNPs | Type of Virus/Pathogen | Characterization of AgNPs | Shape of AgNPs | Size of AgNPs | Viral/Bacterial/Disease Model | Assays/Evaluation Parameters | Mechanism of Action (MOA) | Doses | References |
---|---|---|---|---|---|---|---|---|---|---|
1 | Sputtering deposition on polylactide (PLA) films | Herpes simplex virus type 1, Influenza A virus | WAXS, TEM, TGA, DSC | Not specified | 5.9 nm | In vitro: MDCK, BHK, Hep-2 cells | Antimicrobial, antiviral, and cytotoxicity assays | Weak virucidal effect, not cytotoxic | Not specified | [88] |
2 | Oleylamine-capped AgNPs deposited on nonwoven textile | SARS-CoV-2 | FTIR, DLS, TEM, ICP-OES | Spherical | 8 ± 2 nm | In vitro: Virus inactivation on textile surface | Virus inactivation assay (99.6% in 2 min) | Direct virucidal activity | Microgram amounts | [89] |
3 | Direct pulmonary administration of AgNPs | Influenza virus, Murine pneumonia virus | Not specified | Not specified | Not specified | In vivo: Mice model | Viral load reduction, cytokine analysis, immune response evaluation | Enhances NK cell migration and IFN-γ production | Not specified | [90] |
4 | Green tea extract-mediated synthesis | Foot-and-mouth disease virus (FMDV) | TEM, FTIR, DLS | Spherical | 15.1–16.9 nm (TEM), 28.86 nm (DLS) | In vitro: BHK-21 cells | TCID50, cytopathic effect inhibition assay, IC50, SI | Suppresses viral replication in early stages | IC50: 2.05–2.45 µg/mL | [91] |
5 | In situ functionalization of clinoptilolite with AgNPs using tannic acid | Bacterial pathogens (Gram-positive and Gram-negative) | FTIR, TEM, Compositional analysis | Spherical | 2–4 nm | Not virus-specific (Bacterial model) | Zone of inhibition test | Antibacterial activity via surface adsorption | Not applicable | [92] |
6 | Green synthesis using Trichoderma reesei fungus | SARS-CoV-2 | UV-Vis, TEM, SEM, DLS, Zeta Potential | Spherical | 7–50 nm (TEM), 86.74 nm (DLS major) | In vitro: Vero E6, Calu-3 cells; In vivo: Syrian hamsters | Cytotoxicity (MTT), RT-qPCR, Immunohistochemistry, Inflammasome Activation | Binds spike protein, reduces replication, modulates immune response | Not specified | [93] |
7 | Green and chemical synthesis using Citrus limon extract | Bovine mastitis pathogens (Staphylococcus aureus, E. coli) | UV-Vis, Electron Microscopy, Zeta Sizing, FTIR, GC-MS | Not specified | 10–20 nm | In vitro: Antimicrobial testing | MIC50 (46.10 and 49.93 µg/mL for green AgNPs), MIC50 (77.39 and 86.50 µg/mL for chemical AgNPs) | Disrupts bacterial cell viability | Not specified | [94] |
8 | Green synthesis using Telfairia occidentalis leaves and stems | Not virus-specific (Anti-inflammatory, Anti-diabetic, Antioxidant applications) | UV-Vis, FTIR, SEM | Spherical | 10–80 nm (SEM), 43.66 nm mean | In vitro: Antioxidant, anti-diabetic, and anti-inflammatory assays | α-glucosidase inhibition, protein denaturation inhibition, radical scavenging assays | Phytochemicals stabilize and reduce AgNPs, inhibit enzymes, and neutralize free radicals | Not specified | [95] |
9 | Green synthesis using Cuscuta epithymum extract | Not virus-specific (Antioxidant, Antibacterial, Antitumor properties) | UV-Vis, FESEM, TEM, XRD, FTIR | Spherical | 15–60 nm | In vitro: Antioxidant, antibacterial, and cytotoxicity assays (MCF-7 cells) | DPPH assay (IC50 = 45.55 mg/L), Disk Diffusion for antibacterial activity, MTT cytotoxicity assay (IC50 = 42.53 mg/L, 36.78 mg/L, 26.86 mg/L at 12, 24, 48 h) | Reduction of Ag+ ions to AgNPs, oxidative stress modulation, antibacterial and antitumor activity | Not specified | [96] |
10 | Deep eutectic solvent (DES) method using betaine, glucose, and ethylene glycol | Influenza A/H1N1, Human Coronavirus (HCoV-OC43), Vesicular Stomatitis Virus (VSV) | STEM, XPS, DLS, UV-VIS | Not specified | 50–100 | Human Influenza A/H1N1, HCoV-OC43 (Betacoronavirus 1), VSV (Rhabdoviridae) | ROS generation assays, API assays, MIC/MBC determination, Cell decomposition rate assays | ROS generation leading to enzyme inactivation and inhibition of metabolic processes | Virus titer reduction of 93.7−99.96% | [97] |
11 | Fungal-mediated synthesis using Cephalosporium aphidicola (eco-friendly approach) | Not specified | UV-Vis, FT-IR, EDX, FE-SEM, DLS | Spherical | 59.52 | Not specified | Antibacterial and biofilm degradation assays, DPPH radical scavenging, Alpha-amylase inhibition, Urease inhibition | Antimicrobial, biofilm degradation, enzyme inhibition, antioxidant activity | 1 mg/mL (72.81% DPPH scavenging, 86.06% alpha-amylase inhibition, 80.84% urease inhibition) | [98] |
12 | Green synthesis using Trema orientalis (L.) leaf extract | Not specified | UV-Vis, FTIR, XRD, TEM, AFM | Spherical, Crystalline | 14.04–34.38 (avg. 26.81) | Not specified | Antibacterial assay (Agar well diffusion), MIC | Flavonoids mediate Ag+ reduction and stabilization, leading to antibacterial activity | MIC50 = 55.31 μg/mL; Zone of inhibition: 9, 10, 13, 14 mm at 25, 50, 75, and 100 µg/mL | [48] |
13 | Green synthesis using Garcinia mangostana (GM) peel extract and citric acid for active packaging | Not specified | UV-Vis, Elemental analysis, Silver mapping | Spherical | 2.36–294.73 | Not specified | Virus inactivation assay, Antibacterial (E. coli, Staphylococcus aureus), Water resistance, Tensile strength analysis | Surface roughness increased hydrophobicity, synergistic effect of AgNPs, citric acid, and GM extract | AgNPs-150 coated paper showed complete virus inactivation within 1 min | [99] |
14 | Silver nanoparticles (AgNPs) (20 mg/mL) coated with natural resins from Noble Elements LLC | Influenza A (H1N1), strain A/FM/1/47 | Size: 10 ± 1.5 nm, Stable dispersion, Natural resin coating | Likely spherical (inferred from uniform dispersion) | 10 ± 1.5 | MDCK cells, H1N1 virus (1 × 107 TCID50/mL) | MTT and Neutral Red (CC50 = 80 μg/mL), Virucidal activity, Pre- and Post-exposure assays, Infective titer assay | Prevents viral attachment, disrupts envelope, inhibits replication. Selective Index: Pre-exposure = 88, Post-exposure = 667 (higher than oseltamivir) | 0.0002 to 100 μg/mL tested. Effective concentrations: Pre-exposure = 4.5 μg/mL, Post-exposure = 0.6 μg/mL | [100] |
15 | Green synthesis using Nigella arvensis aqueous extract | HSV-1, HAV, Adenovirus | UV-Vis, XRD, TEM | Spherical | 2–9 (avg. 2.5) | In vitro cell culture | Antiviral efficacy assay, MIC/MBC determination, Color change (yellow to brown) | Inhibits viral replication by 53.6% (HSV-1), 86% (HAV), 17.3% (Adenovirus) | MNTC: 10.56 µg/mL; MIC: 5.7–10.2 μg/mL; MBC: 22.3–36.8 μg/mL | [101] |
16 | Chitosan nanoparticles (CS-NPs) and chitosan silver nanocomposites (CS-Ag NC) | Alfalfa mosaic virus (AMV) in pepper plants | Electron microscopy | Spherical | Uniform | AMV-infected pepper plants | ELISA, Symptomatology, RT-PCR, Agronomic metrics (plant height, fresh and dry pod weight, number of pods) | Induces phenol, proline, and capsaicin production; inhibits AMV replication | 400 ppm CS-NPs (90% inhibition), 200 ppm CS-Ag NC (91% inhibition) | [102] |
17 | Polyvinylpyrrolidone (PVP)-stabilized AgNPs | Spring viraemia of carp virus (SVCV), European catfish virus (ECV), Ictalurid herpesvirus 2 (IcHV-2) | TEM, DLS | Spherical, Electron-dense | 10.2 ± 1.6 (TEM), 22.4 ± 5.3 (DLS) | Fish viruses in EPC cells | Virus pretreatment, Cell pretreatment, Cell post-treatment, Delayed post-treatment (24 h after infection) | Inhibits viral replication, disrupts viral envelope, prevents host cell binding | 25 ng/mL (safe concentration), Reduction in viral load: 70–330× (ECV), 10–54× (SVCV), 5–17× (IcHV-2) | [103] |
18 | Green synthesis using Punica granatum biowaste peel extract | Tobacco mosaic virus (TMV) | SEM, TEM, UV-Vis, XRD, DLS, EDX, FTIR, Zeta potential | Spherical, Condensed | 61–97 (SEM), 33.37 ± 12.7 (TEM) | TMV-infected tomato plants | Greenhouse study (TB, TA, TD treatments), PR gene expression, Oxidative stress markers, Antioxidant enzyme assays | Reduces viral accumulation, delays viral replication, enhances PR gene expression, restores flavonoid biosynthesis | TD strategy (dual treatment) most effective | [104] |
19 | Biological synthesis using fungi | Herpes Simplex Virus and Human Parainfluenza Virus Type 3 | TEM, UV-Vis, zeta potential | Spherical | 46 nm and 40 nm | VERO cells | MTT assay, cotreatment assay, cell pretreatment assay, cell post-treatment assay, Virus pretreatment assay | Inhibits viral replication | ID50-10 mg/mL, | [105] |
21 | Green synthesis using Ulva lactuca extract; AgNO3 (4 mM) + algal extract (5:5) at 60 °C under light for 84 h | Adenovirus Type 2 | UV-Vis, TEM, XRD, SEM | Spherical and distinct AgNPs | 4.08–27.57 nm (avg. 10.29 nm) | In vitro: Vero cell line (African green monkey kidney cells) | MTT (cytotoxicity), Plaque Reduction, TCID50 (viral infectivity) | Weak antiviral activity via possible inhibition of viral entry or replication. Lower activity than Amantadine | 2–3000 µg/mL tested. CC50 = 20.34 µg/mL, 9.83% inhibition at 2 µg/mL | [106] |
22 | Hydroxylamine-reduced Ag colloidal nanoparticles (AgNO3 + NH2OHHCl, 350 rpm, 45 min) | Not applicable (focus on antiviral drug detection) | UV-Vis, DLS (size and distribution) | Spherical | 56.42 nm (average) | Not applicable (focus on Tenofovir (TFV) detection) | SERS, PLS Regression, CHAOS Theory-based Spectral Ranking | AgNPs serve as a SERS substrate, enhancing Raman signals for ultra-sensitive TFV detection, aiding in HIV drug adherence monitoring | TFV detection down to 25 ng/mL, using double-deposition for enhanced sensitivity | [107] |
23 | Green synthesis using Taraxacum officinale (dandelion) root extract; AgNO3 (0.315 g in 100 mL) reduced under alkaline conditions (pH 10) with NaOH, followed by microwave heating | SARS-CoV-2 | XRD, FTIR, FESEM | Spherical | 15–60 nm (FESEM), 11–22 nm (XRD crystallite size) | In vitro: WI-38 human lung fibroblast cells infected with SARS-CoV-2 | XTT assay (cell viability), Plaque Reduction, Microscopic analysis for viral inhibition | Blocks viral entry, disrupts viral proteins, inhibits replication; Alcoholic extract showed stronger antiviral activity due to smaller particle size | 50, 25, and 10 mg/L tested. IC50: 32.50 mg/L (alcoholic), 29.03 mg/L (aqueous) | [108] |
24 | Green synthesis using Alocasia odora rhizome (RE) and stem extract (SE); AgNPs synthesized from aqueous extracts | Dengue virus type 2 (DENV-2) | UV-Vis, SEM, EDX, FTIR | Spherical | RNP: 60.83–64.66 nm, SNP: 54.64–149.06 nm | In vitro: Huh-7 cell line infected with DENV-2 | MTT assay (cytotoxicity), Plaque Reduction, Microscopic analysis for cytopathic effects (CPE) | SNP and RNP significantly reduce viral infectivity titer; SNP shows stronger cytopathic effects against DENV-2 | 12.5 µg/mL: SNP reduces virus-infected cells by 73% ± 2.64, RNP by 70% ± 5 | [109] |
25 | Green synthesis using Solanum mammosum (Sm) leaf extract; AgNPs and AuNPs synthesized using NaBH4 as a reducing agent | PhiX174 (non-enveloped) and Phi6 (enveloped) bacteriophages (surrogate models for SARS-CoV-2) | UV-Vis, TEM, FTIR, HPLC-DAD | Spherical | AuNPs-Sm: 5.34 ± 2.25 nm, AgNPs-Sm: 15.92 ± 8.03 nm | In vitro: Phi6 with Pseudomonas syringae host, PhiX174 with Escherichia coli host | Antiviral assay (viral inactivation), Cytotoxicity assays (A549, HFF cell lines) | AgNPs-Sm and AuNPs-Sm inactivate Phi6, likely by interacting with viral envelope proteins; AgNPs are more effective than AuNPs | AgNPs-Sm: 99.94% viral inactivation at 0.01 mg/mL, AuNPs-Sm: 99.30% at 1 mg/mL | [110] |
S. No | Method of Preparation | Shape and Size | In Vitro/In Vivo | Toxicity and Effects | References |
---|---|---|---|---|---|
1 | Co-precipitation using silver nitrate and trisodium citrate | Spherical, ~25 nm, <40 nm thick | In vitro: Tested on HepG2 and lung cells (IC50 measured) In vivo: Infected mice treated orally; organ biomarkers (ALT, AST, urea, creatinine) assessed | Mild liver and kidney toxicity; reversible with multivitamins. Strong antiparasitic effect and reduced oxidative stress when combined with supplements. | [150] |
2 | Commercial AgNP colloid (Nanocid®) TiO2: Powder suspended and sonicated | Spherical, AgNPs: Avg 7.29 nm TiO2: ~32.3 nm | In vivo only: Common carp exposed to AgNPs, TiO2NPs, or their mixture. Histology, bioaccumulation, enzyme activity, and growth performance assessed | Co-exposure increased toxicity. Caused gill tissue damage, reduced antioxidant enzymes, increased silver bioaccumulation in liver/intestine, and reduced weight gain. | [173] |
3 | Green synthesis using microgreen extract (BCME) + AgNO3 under heat and stirring | Spherical, avg. 34.68 nm Crystalline structure confirmed | In vitro only: Cytotoxicity tested on Vero cells using MTT assay | Low cytotoxicity on Vero cells. Safe for biological use and exhibited strong antimicrobial activity. | [171] |
4 | Green synthesis using “Katti Peptide” + gum arabic protein | Core: 20 ± 5 nm (TEM); Hydrodynamic: 70–80 nm | In vitro: Daphnia similis, zebrafish embryos In vivo: Sprague Dawley rats | EC50 (Daphnia): 4.4 μg/L LC50 (Zebrafish): 177 μg/L No adverse effects in rats up to 10 mg/kg | [165] |
5 | Green synthesis (method not detailed) | Not specified | Plant-based (In vivo) | AgNPs improved growth under Pb stress Reduced oxidative damage; enhanced chlorophyll, antioxidants | [174] |
6 | Aqueous leaf extract of Moringa peregrina | Spherical; 18–27 nm (HR-TEM) | In vitro: MCF-7 and Caco-2 cell lines | IC50: 26.93 μg/mL (MCF-7) IC50: 41.59 μg/mL (Caco-2) Good antioxidant and anticancer activity | [149] |
7 | Green synthesis using methanolic bark extract of Azadirachta indica | Spherical; ~45 nm (SEM) | In vivo: Swiss albino rats | Sub-acute (28 days) and chronic (180 days): No major toxicity up to 10 mg/kg Liver damage at 30 mg/kg | [169] |
8 | Methods not detailed in the document | Spherical; ~2 nm | In vitro (fungal cultures) | Effective against resistant strains Induced ROS, DON production Cellular damage observed | [160] |
9 | Pre-synthesized spherical AgNPs | Spherical, 18–30 nm | In vivo: Female NMRI mice | 4 mg/kg dose led to increased IL-6, IL-1β, reduced pinopods Nanoparticle accumulation in endometrium | [175] |
10 | Commercial AgNPs with coatings (lipoic acid, citrate, BPEI), Ag2S | Spherical; 45–51 nm (TEM) | In vitro: BeWo b30 cell layer + Mouse embryonic stem cell test | Pristine AgNPs slightly cross placenta; embryotoxicity observed only at cytotoxic levels; Ag2S least toxic | [166] |
11 | Chemical reduction (NaBH4 and AgNO3) | Spherical; 55 ± 7 nm | In vitro: HUVECs, bacteria In vivo: C. elegans | Toxic to all systems in a dose-dependent manner; IC50 (HUVECs): 38 μg/mL; reduced motility and reproduction in C. elegans | [151] |
12 | Green synthesis using entomopathogenic fungi | Not specified | In vitro (MTT, Comet assays, pest control bioassays) | Toxic to pests; good antimicrobial activity; low cytotoxicity; potential for eco-friendly biopesticide | [157] |
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Sati, A.; Ranade, T.N.; Mali, S.N.; Yasin, H.K.A.; Samdani, N.; Satpute, N.N.; Yadav, S.; Pratap, A.P. Silver Nanoparticles (AgNPs) as Potential Antiviral Agents: Synthesis, Biophysical Properties, Safety, Challenges and Future Directions─Update Review. Molecules 2025, 30, 2004. https://doi.org/10.3390/molecules30092004
Sati A, Ranade TN, Mali SN, Yasin HKA, Samdani N, Satpute NN, Yadav S, Pratap AP. Silver Nanoparticles (AgNPs) as Potential Antiviral Agents: Synthesis, Biophysical Properties, Safety, Challenges and Future Directions─Update Review. Molecules. 2025; 30(9):2004. https://doi.org/10.3390/molecules30092004
Chicago/Turabian StyleSati, Abhinav, Tanvi N. Ranade, Suraj N. Mali, Haya Khader Ahmad Yasin, Nehal Samdani, Nikil Navnath Satpute, Susmita Yadav, and Amit P. Pratap. 2025. "Silver Nanoparticles (AgNPs) as Potential Antiviral Agents: Synthesis, Biophysical Properties, Safety, Challenges and Future Directions─Update Review" Molecules 30, no. 9: 2004. https://doi.org/10.3390/molecules30092004
APA StyleSati, A., Ranade, T. N., Mali, S. N., Yasin, H. K. A., Samdani, N., Satpute, N. N., Yadav, S., & Pratap, A. P. (2025). Silver Nanoparticles (AgNPs) as Potential Antiviral Agents: Synthesis, Biophysical Properties, Safety, Challenges and Future Directions─Update Review. Molecules, 30(9), 2004. https://doi.org/10.3390/molecules30092004