Bosso Andrea, Masino Antonio, Di Nardo Ilaria, Zannella Carla, Gaglione Rosa, Palumbo Ida, Culurciello Rosanna, De Filippis Anna, Torres Marcelo D T, de la Fuente-Nunez Cesar, Galdiero Massimiliano, Arciello Angela, Di Maro Antimo, Pizzo Elio, Cafaro Valeria, Notomista Eugenio
Department of Biology, University of Naples Federico II, Via Vicinale Cupa Cintia, 26, 80126 Naples, Italy.
Department of Translational Medical Science, University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2025 Sep 12;26(18):8914. doi: 10.3390/ijms26188914.
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 (FIBα, FIBβ, and FIBγ), 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.
纤维蛋白原（FIB）是凝血级联反应的关键成分，传统上因其在止血和组织修复中的作用而被认可。然而，由于其在血浆中的丰度较高，且在炎症过程中易受蛋白水解切割，它可能也是一种以前未被认识的生物活性肽来源。本研究首次对源自人纤维蛋白原三个亚基（FIBα、FIBβ和FIBγ）C末端的六种阳离子抗菌肽（AMPs）的抗菌、抗炎和抗病毒特性进行了全面分析，这些抗菌肽是使用我们团队开发的评分函数鉴定出来的。针对革兰氏阳性和革兰氏阴性病原体的抗菌试验显示，根据其母体蛋白的不同，抗菌活性谱也不同。选定的肽与传统抗生素或凝血酶衍生肽（P）GKY20联合使用时表现出相加或协同作用，突出了它们在联合治疗中的潜力。溶血试验证实了纤维蛋白原衍生的隐蔽肽与红细胞的生物相容性。此外，这些肽显著降低了LPS诱导的小鼠巨噬细胞Raw 264.7细胞中一氧化氮的释放，表明具有抗炎活性。值得注意的是，在各种治疗条件下均观察到对包膜病毒（HCoV-229E和HSV-1）的抗病毒活性，而对非包膜病毒CVB3未检测到活性。总体而言，这些发现揭示了人纤维蛋白原是多功能隐蔽肽的来源，具有广谱抗菌、抗病毒和免疫调节活性，支持了它们作为先天免疫系统一部分的潜力。
