Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology

Abstract

Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer. Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients. Aim. The objective of this study was to assess the pharmacological mechanisms and targets of oxymatrine in relation to COVID-19 lung cancer. Methodology. Utilizing network pharmacology analysis, a selection of 2628 genes were identified as co-targets for both COVID-19 and lung cancer. Subsequently, a clinicopathological analysis was conducted by integrating RNA-Seq and clinical data obtained from the TCGA-LUAD lung cancer dataset, which was acquired from the official TCGA website. The identification of pharmacological targets for oxymatrine was accomplished through the utilization of various databases including Pharm mapper, SWISS Target prediction, and STITCH. These identified targets were further investigated for protein-protein interaction (PPI) using STRING, as well as for gene ontology (GO) and KEGG pathways. Results. The effects of oxymatrine on COVID-19-induced lung cancer were mediated by immune regulation, cytoprotection, antiviral, and anti-inflammatory activities, immune regulation, and control of related signalling pathways, including the formation of the neutrophil extracellular trap, phagosome, Toll-like receptor signalling pathway, apoptosis, proteoglycans in cancer, extracellular matrix disassembly, and proteolysis involved in cellular protein catabolism. Furthermore, important substances and genes like ALB, MMP3, MMP1, and TLR4 may affect how oxymatrine suppresses lung cancer/COVID-19 development. Conclusion. To treat COVID-19 or lung cancer paired with COVID-19, oxymatrine may improve the therapeutic efficacy of current clinical antiviral medicines and immunotherapy.