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In this study, we report a novel, green biosynthesis of SeNPs using\n                    <jats:italic>Limosilactobacillus fermentum<\/jats:italic>\n                    , followed by functionalization with chitosan to produce Se\/CS nanocomposites with enhanced antiviral performance against SARS-CoV-2.\n                    <jats:italic>L. fermentum<\/jats:italic>\n                    was used to biosynthesize SeNPs, providing a rapid, safe, and environmentally friendly approach. The production process was optimized by testing different parameters such as concentrations of Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    , temperature, ratios between cell-free bacterial metabolites and Na\n                    <jats:sub>2<\/jats:sub>\n                    SeO\n                    <jats:sub>3<\/jats:sub>\n                    , and pH. UV\u2013Vis spectroscopy, FT-IR, XRD, Zeta potential, and TEM studies confirmed the successful synthesis of Se\/CS NC, with a distinctive peak at 266\u00a0nm. FT-IR also showed that proteins were present as capping and stabilizing agents in Se\/CS NC. Se\/CS NC has a high zeta potential with a negative net surface charge of \u2212\u200921.84\u2009\u00b1\u20094.7 mV, giving Se\/CS NC great stability. Se\/CS NC had an average particle size of 38.19\u00a0nm and exhibited a crystalline morphology. Biological assays in SARS-CoV-2-infected Vero E6 cells revealed that SeNPs alone displayed dose-dependent cytotoxicity, reducing cell viability above 125\u00a0\u00b5g\/ml. In contrast, Se\/CS NC maintained over 96% cell viability at all tested concentrations and demonstrated potent antiviral activity, achieving over 95% inhibition of viral replication at concentrations\u2009\u2265\u2009250\u00a0\u00b5g\/ml. Studies identified virucidal action as the primary antiviral mechanism, with 47.4% inhibition at 500\u00a0\u00b5g\/ml. To the best of our knowledge, this study provides the first experimental evidence that green-synthesized Se\/CS NC produced by\n                    <jats:italic>L. fermentum<\/jats:italic>\n                    can effectively inhibit SARS-CoV-2, highlighting their potential as a safe, eco-friendly antiviral candidate for future COVID-19 therapies and pharmaceutical applications. This demonstrates a direct application of nanotechnology in combating COVID-19 by suppressing viral replication and maintaining host cell viability.\n                  <\/jats:p>","DOI":"10.1186\/s11671-025-04420-6","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:16:58Z","timestamp":1768799818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antiviral activity of green synthesized selenium nanoparticles alone and in combination with chitosan against SARS-CoV-2"],"prefix":"10.1186","volume":"21","author":[{"given":"Mohamed M.","family":"El-Zahed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Kandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud E.","family":"Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"4420_CR1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12985-022-01814-1","volume":"19","author":"S Montazersaheb","year":"2022","unstructured":"Montazersaheb S, Hosseiniyan Khatibi SM, Hejazi MS, Tarhriz V, Farjami A, Ghasemian Sorbeni F, et al. 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