Anti-RSV drug screening and inhibition of RSV infection by lapatinib through the IL-17 pathway

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children worldwide. Safe and effective treatments for RSV remain limited. In this investigation, we screened more than 100 anti-influenza compounds from a small-molecule library using an A549 cell model. Among these drugs, lapatinib emerged as a promising candidate and demonstrated potent anti-RSV activity along with low cytotoxicity. Lapatinib not only significantly suppressed RSV replication in vitro but also markedly reduced viral proliferation and mitigated inflammatory lung injury in a BALB/c female mouse model. Mechanistic studies revealed that lapatinib inhibited RSV replication through the downregulation of interleukin-17 (IL-17). This effect was antagonized upon IL-17 overexpression, confirming the pivotal role of this cytokine. We further proposed that lapatinib exerted its antiviral effect by targeting ErbB1 and ErbB2 receptors, thereby disrupting IL-17–mediated viral propagation. These findings provide both novel mechanistic insights and a compelling therapeutic direction for the treatment of RSV infection。.