Antiviral metabolites from <i>Passiflora edulis</i>: An in vitro, phytochemical, and computational studies

Yellow fever (YF) is a mosquito-borne virus with high mortality rates, affecting regions in South America and Africa. Despite the effectiveness of YF vaccines, increased global demand and reports of rare, severe side effects have spurred the search for safer therapeutic alternatives. Current treatments lack specific antiviral drugs approved for YF, underscoring the need for new, effective therapies. This study investigated the potential of Passiflora edulis f. edulis leaf and stem extracts as antiviral agents against the yellow fever virus (YFV). In vitro tests showed that the extracts significantly reduced YFV viral loads by twofold in Huh-7 cells and 1.5-fold in Vero-h-Slam cells at a concentration of 50 µg/mL, with a smaller reduction at 25 µg/mL and no cytotoxic effects on either cell line. Phytochemical analysis identified a new C-deoxyhexosyl flavone, luteolin-8-(1-C-β-boivinopyranosyl)-4'1-O-β-d-glucopyranoside, along with several known compounds. Protein-protein interaction (PPI) network analysis using the STRING database and Cytoscape software revealed key hub genes, including IFNA1, IL7R, CD19, IL2RA, and IFNG, crucial in antiviral defense. Molecular docking studies further evaluated how these compounds interact with the YFV NS2B-NS3 protease, essential for viral replication. Molecular dynamics (MD) simulations confirmed the stability of these interactions over a 120-nanosecond period, supporting the compounds' antiviral potential. This study demonstrates the promise of Passiflora edulis metabolites as a foundation for developing novel YFV therapies by combining computational and experimental insights.