Cynarin Targets Host CX3CR1 for Dual-Action Prophylaxis against RSV Infection and Pulmonary Pathology

Abstract Safe, small-molecule prophylactic agents against respiratory syncytial virus (RSV) are critically lacking. Here, we identify Cynarin, an artichoke-derived dietary polyphenol, as a micromolar affinity CX3CR1 antagonist. Mechanistically, Cynarin confers dual-action protection through two distinct routes: it acts as a “chemical shield” to competitively block viral entry at the epithelial interface by binding CX3CR1, and through a separate CX3CR1-independent mechanism, exhibits intrinsic, virus-independent anti-inflammatory properties by directly suppressing macrophage activation. This target-based interaction was rigorously validated via biochemical and functional assays. In an RSV-infected mouse model, prophylactic administration of Cynarin demonstrated superior efficacy over therapeutic treatment. It significantly reduced pulmonary viral load, ameliorated lung consolidation, and potently suppressed the RSV-induced cytokine storm. Collectively, our findings establish a novel host-directed strategy utilizing Cynarin to target CX3CR1, highlighting the translational potential of food-derived bioactives in offering a dual prophylactic safeguard against viral infection and associated pulmonary pathology.