{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:50:46Z","timestamp":1791874246268,"version":"4.3.4"},"reference-count":98,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibrinogen (FIB), a key component of the coagulation cascade, is traditionally recognized for its role in hemostasis and tissue repair. However, due to its high plasma abundance and susceptibility to proteolytic cleavage during inflammation, it may also represent a previously unrecognized source of bioactive peptides. This study presents, for the first time, a comprehensive analysis of the antimicrobial, anti-inflammatory, and antiviral properties of six cationic antimicrobial peptides (AMPs) deriving from the C-terminal extremities of the three subunits of human fibrinogen (FIB\u03b1, FIB\u03b2, and FIB\u03b3), identified using a scoring function developed by our group. Antibacterial assays against Gram-positive and Gram-negative pathogens revealed different antimicrobial activity profile depending on their parent protein. Selected peptides displayed additive or synergistic effects when combined with conventional antibiotics or the thrombin-derived peptide (P)GKY20, highlighting their potential for combination therapies. Hemolytic assay confirmed the biocompatibility of fibrinogen-derived cryptic peptides with erythrocytes. Furthermore, the peptides significantly reduced LPS-induced nitric oxide release in murine macrophages Raw 264.7 cells, indicating anti-inflammatory activity. Notably, antiviral activity was observed against enveloped viruses (HCoV-229E and HSV-1) under various treatment conditions, while no activity was detected against the non-enveloped virus CVB3. Overall, these findings reveal human fibrinogen as a source of multifunctional cryptic peptides with broad-spectrum antimicrobial, antiviral, and immunomodulatory activities, supporting their potential as part of the innate immune system.<\/jats:p>","DOI":"10.3390\/ijms26188914","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T07:33:02Z","timestamp":1758007982000},"page":"8914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Antimicrobial and Antiviral Properties of Cryptic Peptides from Human Fibrinogen"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-300X","authenticated-orcid":false,"given":"Andrea","family":"Bosso","sequence":"first","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-8217","authenticated-orcid":false,"given":"Antonio","family":"Masino","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy"},{"name":"Department of Translational Medical Science, University of Naples Federico II, 80131 Naples, Italy"},{"name":"ImmunoNutritionLab at CEINGE Advanced Biotechnologies, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-4801","authenticated-orcid":false,"given":"Ilaria","family":"Di Nardo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7991-8700","authenticated-orcid":false,"given":"Carla","family":"Zannella","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-0237","authenticated-orcid":false,"given":"Rosa","family":"Gaglione","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0450-0616","authenticated-orcid":false,"given":"Ida","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7083-2908","authenticated-orcid":false,"given":"Rosanna","family":"Culurciello","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-7962","authenticated-orcid":false,"given":"Anna","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-9138","authenticated-orcid":false,"given":"Marcelo D. 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