Inhibition of hepatitis C virus by Avicennia marina (Forssk.) Vierh. leaves extract: Liquid chromatography-high-resolution mass spectrometry, network pharmacology, molecular simulation, and in vitro study

Abstract

Introduction: Avicennia marina (Forssk.) Vierh. is known for its antiviral property. However, therapeutic mechanisms of the plant against hepatitis C virus (HCV) are still unclear. Therefore, this study aimed to determine the potential of A. marina leaves extract to inhibit HCV infection. The study procedures were carried out using a network pharmacology approach based on liquid chromatography-high-resolution mass spectrometry (LC-HRMS) data. Methods: LC-HRMS was performed to identify the chemical composition of A. marina methanolic extract, while network pharmacology was carried out to determine protein targets and signaling pathways in HCV associated with A. marina. In addition, molecular docking and dynamic simulations were used to understand molecular interaction of each single compound with its single protein target, followed by in vitro testing to validate the computational results. Results: The results of LC-HRMS analysis identified the presence of 74 compounds in the extract, with 70 adhering to Lipinski’s Rule of Five. Network pharmacology analysis showed 88 potential therapeutic targets. Molecular docking performed on the top 3 protein targets (Interleukin-6/IL-6, signal transducer and activator of transcription 3/STAT3, and tumor necrosis factor-α/TNF-α) showed that 2 compounds, Comp28 and Comp63, had the potential to inhibit IL-6, while 3 compounds, Comp4, Comp7, and Comp48, were identified as potential inhibitors of TNF-α. In vitro test against HCV demonstrated an IC50 value of 12.664 ± 0.984 µg/mL. Conclusion: This study suggests that A. marina leaves extract can act on IL-6, STAT3, and TNF for inhibiting HCV.