Abstract

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections and related deaths in infants, young children, and the elderly. The clinical management of RSV is challenging due to its high mutation rate and the limited efficacy and safety of existing antiviral drugs. Sophora alkaloids, natural compounds derived from Sophora flavescens , exhibit broad-spectrum antiviral and immunomodulatory activities. Mechanistically, RSV relies on ERK1/2 phosphorylation to facilitate viral replication and spread, while sophora alkaloids inhibit ERK1/2 phosphorylation via regulating MEK/ERK signaling pathway, thereby suppressing viral proliferation and the inflammatory response caused by RSV infection. In vivo studies demonstrated that sophora alkaloids significantly reduced the mortality of RSV-infected mice via intratracheal administration. To further enhance the pulmonary retention of drugs, liposomes were used to improve the therapeutic effects of sophora alkaloids. As the most effective sophora alkaloids against RSV infection, sophocarpine (SC) was encapsulated in liposomes to enhance its anti-RSV infection effect. In vivo studies demonstrate that SC-loaded liposomes outperformed the free SC in suppressing RSV replication and alleviating pulmonary inflammation in murine models of RSV infection. This study not only clarifies the mechanism by which sophora alkaloids counteract RSV-infection but also provides liposomal formulation of SC to improve the anti-RSV therapeutic effects.