Unveiling the Mechanisms of Liujunzi Decoction in COVID-19/Lung Cancer Comorbidity: A Network Pharmacology and Molecular Docking Study

OBJECTIVE: This study aimed to investigate the mechanism of action of Liujunzi decoction (LJZD) in the treatment of coronavirus disease 2019 (COVID-19) combined with lung cancer based on network pharmacology and molecular docking. METHODS: First, we screened target information related to LJZD, COVID-19, and lung cancer from public databases, such as TCMSP, GeneCards, Drugbank, OMIM, and TTD. Then, we used the Evenn platform, String online database, and Cytoscape 3.7.1 software to obtain the common drug-disease targets and construct a PPI network and a "herb-ingredient-target" network. Next, we selected core targets based on their degree values and performed GO and KEGG enrichment analysis using the Metascape database and bioinformatics platforms. We then conducted molecular docking analysis using software, like AutoDockTools and Vina, to compare the binding affinity between core targets and key ingredients of Liujunzi decoction and core targets with Nutlin-3a. Finally, we performed molecular dynamics simulations on AKT1 and quercetin using the GROMACS software. RESULTS: A total of 125 active ingredients of LJZD were screened, of which 107 could bind to 94 common targets and exert therapeutic effects. The common targets were mainly enriched in 1807 GO-enriched entries and 191 KEGG signaling pathways. Molecular docking confirmed a strong affinity between the core target and key components, as well as a binding mode of the key components of Liujunzi decoction similar to TP53 activator Nutlin-3a. The molecular dynamics simulation results indicated AKT1 to bind to quercetin in a stable and tight manner. DISCUSSION: This first systematic network pharmacology study of LJZD in COVID-19/lung cancer comorbidity reveals that its therapeutic potential likely arises from synergistic interactions among multiple active compounds (notably quercetin and β-sitosterol) and core targets (TP53, AKT1, VEGFA). This multi-target profile aligns with the TCM principle of "treating different diseases with the same treatment. The comparable binding affinity of LJZD components to the TP53 activator Nutlin-3a suggests a shared mechanistic basis. Enrichment of pathways central to both diseases-including HIF-1 (hypoxia/angiogenesis) and AGE-RAGE (inflammation/ fibrosis)-indicates that LJZD may simultaneously modulate shared pathological processes. These computational findings provide a pharmacological rationale for LJZD's clinical application and establish a foundation for future experimental validation. CONCLUSION: LJZD may achieve the goal of treating COVID-19/lung cancer patients by potentially acting on genes, such as TP53, AKT1, VEGFA, and regulating signaling pathways and biological cellular processes, including pathways of cancer, lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, cell senescence, chemical cancer-reactive oxygen species, and HIF-1 signaling pathway, through active ingredients, such as quercetin, β-sitosterol, and others.