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Targeting Matrix Metalloproteinase-1, Matrix Metalloproteinase-7, and Serine Protease Inhibitor E1: Implications in preserving lung vascular endothelial integrity and immune modulation in COVID-19.
Int. J. Biol. Macromol. 306:141602 (2025)
BACKGROUND: SARS-CoV-2 disrupts lung vascular endothelial integrity, contributing to severe COVID-19 complications. However, the molecular mechanisms driving endothelial dysfunction remain underexplored, and targeted therapeutic strategies are lacking. OBJECTIVE: This study investigates Naringenin-7-O-glucoside (N7G) as a multi-target therapeutic candidate for modulating vascular integrity and immune response by inhibiting MMP1, MMP7, and SERPINE1-key regulators of extracellular matrix (ECM) remodeling and inflammation. METHODS & RESULTS: RNA-set analysis of COVID-19 lung tissues identified 17 upregulated N7G targets, including MMP1, MMP7, and SERPINE1, with the latter exhibiting the highest expression. PPI network analysis linked these targets to ECM degradation, IL-17, HIF-1, and AGE-RAGE signaling pathways, and endothelial dysfunction. Disease enrichment associated these genes with idiopathic pulmonary fibrosis and asthma. Molecular docking, 200 ns MD simulations (triplicate), and MMGBSA calculations confirmed N7G's stable binding affinity to MMP1, MMP7, and SERPINE1. Immune profiling revealed increased neutrophils and activated CD4+ T cells, alongside reduced mast cells, NK cells, and naïve B cells, indicating immune dysregulation. Correlation analysis linked MMP1, MMP7, and SERPINE1 to distinct immune cell populations, supporting N7G's immunomodulatory role. CONCLUSION: These findings suggest that N7G exhibits multi-target therapeutic potential by modulating vascular integrity, ECM remodeling, and immune dysregulation, positioning it as a promising candidate for mitigating COVID-19-associated endothelial dysfunction.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Covid19 ; Immune Modulation ; Lung Endothelial Cells; Plasminogen-activator Inhibitor-1; Induced Apoptosis; Ve-cadherin; Web Server; Naringin; Naringenin-7-o-glucoside; Doxorubicin; Expression; Prunin; Cells
ISSN (print) / ISBN
0141-8130
e-ISSN
1879-0003
Quellenangaben
Volume: 306,
Article Number: 141602
Publisher
Elsevier
Publishing Place
Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)
Grants
Government of India
DBT-JRF and SRF from Govt. of India
Banaras Hindu University, Government of India
DBT-JRF and SRF from Govt. of India
Banaras Hindu University, Government of India