Abstract
Background: Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms.
Methods: Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug’s therapeutic targets and potential mechanisms for anti-LUAD/COVID-19.
Results: We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Conclusions: This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.
Keywords: Bioinformatics analyses; COVID-19; Emetine; Lung adenocarcinoma; Molecular docking; Molecular dynamics.
【저자키워드】 COVID-19, molecular docking, molecular dynamics., lung adenocarcinoma, bioinformatics analyses, Emetine, 【초록키워드】 coronavirus disease, Transcriptome, SARS-CoV-2, Tumor, Coronavirus disease 2019, coronavirus, Prognosis, furin, IL6, drugs, molecular docking, network pharmacology, risk, drug, docking, molecular dynamics, protease, severe acute respiratory syndrome Coronavirus, MD simulation, DPP4, Replication, MPro, Screen, Patient, lung adenocarcinoma, target, network, molecular, binding, BTK, Analysis, Emetine, therapeutic target, CCL20, TRPA1, acute respiratory syndrome, acute respiratory syndrome coronavirus, potential mechanism, acute respiratory syndrome coronavirus 2, potential mechanisms, Intersection, connectivity, SERPING1, replication of SARS-CoV-2, PRF1, LDHA, effective, DDP4, ENhance, SDK1, SLC6A4, tumor immunity, ZIC5, performed, lack, inhibit, conducted, screened, exhibited, analysis, groups, differentially expressed, Map, Atla, Cox proportional hazard, MIF, 【제목키워드】 bioinformatics, lung, Molecular simulation, potential mechanism, analysis,