Molecular Mechanism of Avicennia marina (Forssk.) Vierh. in Inhibiting Hepatitis C Virus Based on Network Pharmacology and Molecular Docking

Abstract

Hepatitis C virus (HCV) infection is a significant threat to human health, with a high prevalence in various countries around the world. To reduce its prevalence, natural resources have been reported to provide diverse structures and fewer side effects for developing anti-HCV treatments. Therefore, this study aims to assess the potential of Avicennia Marina (Forssk.) Vierh. (AM) to inhibit HCV infection using network pharmacology and molecular docking methods. The results identified the presence of 12 compounds and 11 core targets, including SRC, AKT1, tumor necrosis factor-α (TNF-α), HSP90AA1, EGFR, BCL2, JUN, PI3KCA, ESR1, CASP3, and HIF1A. In addition, 5 key targets, SRC, AKT1, TNF, HSP90AA1, and ESR1, met the criteria for Degree, Closeness, and Centrality. Molecular docking revealed that several compounds had lower binding energy than native ligands when bound to AKT1, TNF-α, and HSP90AA1. Avicennone D effectively inhibited AKT1 (binding energy of-7.074 kcal/mol) and TNF-α (binding energy of-5.282 kcal/mol), while Avicenol C and Avicennone F showed strong potentials against TNF-α (binding energy of each-6.151 kcal/mol and-5.622 kcal/mol, respectively) and HSP90AA1 (binding energy of each-10.369 kcal/mol and-9.525 kcal/mol, respectively). The inhibition results showed that Stenorpoquinone B had the potential to inhibit TNF-α (binding energy of-6.030 kcal/mol). A total of 10 compounds, including Avicenol A, Avicenol C, Avicequinone A, Avicequinone C, and Avicennone A-G, demonstrated comparable or superior binding energy to the native ligand for HSP90AA1. This study provided insights into molecular mechanisms through which AM could treat HCV infections by targeting key proteins.