Theaflavins suppresses RSV infection by modulating the MAVS-I-IFN pathway.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in infants and the elderly, and no effective therapeutics are currently available. Previous studies have indicated the antiviral potential of theaflavins, yet their anti-RSV activity and underlying mechanisms remain incompletely elucidated. In this study, using RSV as a model, we evaluated the antiviral efficacy of theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate in HEp-2 cells and A549 cells, and found that they inhibit post-entry viral replication. In an RSV-infected mouse model, theaflavins treatment significantly reduced pulmonary viral load and RSV F protein expression (detected by immunohistochemistry), confirming inhibition of RSV replication. Treatment concurrently alleviated systemic inflammation, reduced fever, and prevented weight loss. Furthermore, we demonstrated that theaflavin-3'-gallate and theaflavin-3,3'-digallate directly bind mitochondrial antiviral-signaling protein, inducing interferon production and stimulating the antiviral innate immune response. Collectively, these findings establish theaflavins as effective inhibitors of RSV infection and suggests their potential as candidate anti-RSV agents.