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

Abstract

BACKGROUND:

Respiratory syncytial virus (RSV) is the leading cause of mortality and morbidity in children under the age of five. Despite this, there is still a lack of 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 effects of andrographolide on RSV were analyzed via RSV N gene load and proinflammatory cytokine levels. The RNA transcriptome was sequenced, and data were analyzed by R software. Andrographolide-related target genes were extracted via network pharmacology using online databases. Lentiviral transfection was applied to knockdown the heme oxygenase-1 gene (Hmox1, HO-1). Results showed that andrographolide suppressed RSV replication and attenuated subsequent inflammation. Network pharmacology and RNA sequencing analysis indicated that the hub gene HO-1 may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, andrographolide exerted 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 expression in human airway epithelial cells, providing novel insights into potential therapeutic targets and drug repurposing in RSV infection.

• Authors: Siyi Che, Na Zhou, Ying Liu, Jun Xie, Enmei Liu
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 50 Issue 5 Pg. 4261-4272 (May 2023) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 36918433 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• andrographolide
• Antiviral Agents
• Heme Oxygenase-1
• Interferons
• Diterpenes

Topics

• Child
• Humans
• Antiviral Agents (pharmacology)
• Epithelial Cells (metabolism)
• Heme Oxygenase-1 (drug effects, genetics)
• Interferons (drug effects, metabolism)
• Respiratory Syncytial Virus Infections (drug therapy, metabolism)
• Respiratory Syncytial Virus, Human (genetics, pathogenicity)
• Diterpenes (pharmacology, therapeutic use)