Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells

Abstract

Abstract Background: Respiratory syncytial virus (RSV), the leading cause of mortality and morbidity in children under the age of five, is still lacking in safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear.Methods and results: In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effect of andrographolide on RSV was analyzed via RSV N gene load and proinflammatory levels. The RNA transcriptome was sequenced and data were analyzed by R software. Lentivirus was transfected to knockdown the expression of HO-1. Results showed andrographolide suppressed RSV replication and attenuated subsequent inflammation. RNA sequencing indicated that the hub gene heme oxygenase-1 (HO-1) may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, results verified that andrographolide exert antiviral effects against RSV partially by inducing HO-1, but did not activate the antiviral interferon response. Conclusion: Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 in human airway epithelial cells, which may provide novel insights into potential therapeutic targets and drug repurposing in RSV infection.