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Thus, search for safe and effective alternative treatments is urgently needed.\n                    <jats:italic>Peganum harmala<\/jats:italic>\n                    L. (\n                    <jats:italic>P. harmala<\/jats:italic>\n                    ) praised with antiviral potential may afford a decent option against HSV-1. This study creatively integrated network pharmacology and nanoscience to objectively disclose the efficacy mechanism of\n                    <jats:italic>P. harmala<\/jats:italic>\n                    bioactive compounds and augment the antiviral potential of\n                    <jats:italic>P. harmala<\/jats:italic>\n                    against HSV-1 via nanotechnology. Network pharmacology analysis revealed MAPK 1, SRC, EGFR and JAK1 as the top putative HSV-1 genes highly enriched in MAPK, PI3K-Akt, and JAK-STAT signalling pathways and primarily associated with the efficacy mechanism of\n                    <jats:italic>P. harmala<\/jats:italic>\n                    bioactive compounds against HSV-1. Complementarily, four\n                    <jats:italic>P. harmala<\/jats:italic>\n                    nano-formulations were established, monitored using different pharmaceutical scores, and assessed against HSV-1 using plaque reduction assay. Experimentally speaking,\n                    <jats:italic>P. harmala<\/jats:italic>\n                    -CS-ZnO NPs showed higher zeta (+\u200940.8) with particle-size (73.06\u00a0nm), higher entrapment (81.7%) with loading-capacity (6.8%), sustained release reaching 50.5% after 24\u00a0h and demonstrated the most promising observation against HSV-1, with viral inhibition of 54.1% which is double the effect of crude extract alone with acceptable cytotoxicity (CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009271.4\u00a0\u00b5g\/ml). This enhanced effect is possibly due to the synergistic antiviral properties of\n                    <jats:italic>P. harmala<\/jats:italic>\n                    bioactive compounds, chitosan, and zinc oxide nanoparticles. This complex between the ingredients chemically detected by FT-IR analysis also improved stability, cellular uptake, viral inhibition, and bioavailability. Our findings offer a solid basis for more extensive and rational clinical integration of\n                    <jats:italic>P. harmala<\/jats:italic>\n                    in the pharmaceutical industry to rectify human herpes viruses.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-24155-9","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:23:48Z","timestamp":1763465028000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparison of Peganum harmala L. leaves extract nanoformulations against herpes simplex virus type 1 guided by network pharmacology analysis"],"prefix":"10.1038","volume":"15","author":[{"given":"Basant A.","family":"Abou-Taleb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya M.","family":"Elbanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala M.","family":"Hammoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim A.","family":"Abdelwahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.","family":"Mohyeldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina S.","family":"Ghallab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"5","key":"24155_CR1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2471\/BLT.19.237149","volume":"98","author":"C James","year":"2020","unstructured":"James, C. et al. 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