Network pharmacology and molecular docking reveal antiviral mechanisms of silver nanoparticles synthesized by Oscillatoria sp. against HCV pathogenesis

초록

This study explored the green synthesis of silver nanoparticles (AgNPs) using eco-friendly aqueous and methanolic extracts from Oscillatoria sp. algae. Characterization techniques (Fourier transform infrared spectroscopy, Transmission electron microscopy, Dynamic light scattering technique, and Zeta potential) confirmed the successful synthesis and stability of the AgNPs. Untargeted metabolic profiling via LC-MS tentatively identified 22 potential metabolites (1-22) in the extracts, primarily glycolipids, macrolides, fatty acids, and cyclic polyketides. Notably, the methanolic extract and its derived AgNPs exhibited potent antiviral activity against the Hepatitis C Virus (HCV) in HuH7.5 cells. The AgNPs displayed a significantly lower IC50 (0.0705 mu g/mL) than the raw extract (20.325 mu g/mL). Meanwhile, formulations showed little effect on normal cell lines (HuH7, THLE2). Network pharmacology analysis revealed the therapeutic potential of Oscillatoria sp. against HCV by targeting key genes. Subsequent molecular docking simulations identified o-anisic acid methyl ester (2), oscillaginin B (11), and methyl-11-octadecenoate (14) as promising antiviral candidates. These compounds exhibited strong binding affinities (binding energy < -5.0 kcal/mol) with Albumin (ALB) and Cluster of Differentiation 4 (CD4), suggesting their potential role in modulating critical pathways for viral infection and liver function. The increased antiviral effect of the AgNPs compared to crude extracts can be attributed to their ability to enhance the delivery of metabolites and improve their bioavailability. Additionally, the strong interactions between the identified metabolites and ALB and CD4 indicate a modulation of host-virus interactions, as well as key pathways involved in HCV entry and liver function. This provides a mechanistic explanation for the observed therapeutic potential. Overall, this work highlights the potential of Oscillatoria sp. metabolites and their biogenic AgNPs for combating HCV and paves the way for discovering novel antiviral agents from natural sources.

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