Deciphering the potential therapeutic targets and mechanisms of jaranol for the treatment of COVID-19 and lung adenocarcinoma

Abstract

Patients with lung adenocarcinoma (LUAD) are vulnerable to COVID-19. However, there is currently a lack of available treatments for LUAD patients infected with COVID-19. Jaranol is a naturally derived flavonoid that exhibits promising properties as an antiviral and antitumor agent. Therefore, this research intends to investigate the molecular targets and underlying mechanisms of jaranol for the treatment of COVID-19/LUAD. Through network pharmacology, 47 intersection target genes were identified for jaranol against COVID-19/LUAD, and an eight-gene risk score model with strong predictive accuracy for LUAD patients was constructed. Functional enrichment analysis demonstrated that the main mechanism of jaranol in combating COVID-19/LUAD involved the regulation of response to hormone, positive regulation of phosphorylation, and PI3K-Akt signaling pathway. Furthermore, the results of molecular docking analysis indicated that jaranol exhibited a significant affinity with eight hub targets (AKT1, SRC, EGFR, HSP90AA1, ESR1, PTGS2, PPARG, and MMP9) as well as three core COVID-19-related targets (ACE2, 3CLpro, and PLpro). The direct binding between jaranol and MMP9 was then validated in A549 lung cancer cells using cellular thermal shift assay (CETSA). These findings suggest that jaranol has a promising therapeutic effect against COVID-19/LUAD, providing a theoretical foundation and novel perspectives for future development as a potential pharmaceutical candidate.

Keywords

• Jaranol
• COVID-19
• Lung adenocarcinoma
• Network pharmacology