AUTHOR=Wu Wen-yu , Jiao Xin , Song Wen-xin , Wu Peng , Xiao Pei-qi , Huang Xiu-fang , Wang Kai , Zhan Shao-feng 

TITLE=Network pharmacology and bioinformatics analysis identifies potential therapeutic targets of Naringenin against COVID-19/LUSC

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1187882

DOI=10.3389/fendo.2023.1187882

ISSN=1664-2392

ABSTRACT=Coronavirus disease 2019(COVID‐19)  is a highly contagious respiratory disease that has posed a serious threat to people’s daily lives and caused an unprecedented challenge to public health and people's health worldwide. Lung squamous cell carcinoma(LUSC) is a common type of lung malignancy with a highly aggressive nature and poor prognosis. Patients with LUSC could be at risk for COVID-19. We conducted this study to examine the potential for naringenin to develop into an ideal medicine and investigate the underlying action mechanisms of naringenin in COVID-19 and LUSC due to the anti-viral, anti-tumor, and anti-inflammatory activities of naringenin. We discovered numerous COVID-19/LUSC target genes and examined their prognostic value in LUSC patients utilizing a variety of bioinformatics and network pharmacology methods. Furthermore, a risk score model with strong predictive performance was developed based on these target genes to assess the prognosis of LUSC patients with COVID-19. We intersected the therapeutic target genes of naringenin with the LUSC, COVID-19-related targets, and identified 354 common targets, which could be used as potential target genes for naringenin to treat COVID-19/LUSC. The treatment of COVID-19/LUSC with naringenin may involve oxidative stress, anti-inflammatory, antiviral, antiviral, apoptosis, immunological, and multiple pathways containing PI3K-Akt, HIF-1, and VEGF, according to the results of the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of these 354 common targets. By constructing a protein-protein interaction(PPI) network, we ascertained AKT1, TP53, SRC, MAPK1, MAPK3, and HSP90AA1 as possible hub targets of naringenin for the treatment of COVID-19/LUSC. Last but not least, molecular docking investigations showed that naringenin has strong binding activity in COVID-19/LUSC. Overall, we revealed for the first time the pharmacological targets and potential molecular processes of naringenin for the treatment of COVID-19/LUSC. However, these results need to be confirmed by additional research and validation in real LUSC patients with COVID-19.