Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses

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.

Analysis of the potential relationship between COVID-19 and Behcet’s disease using transcriptome data

“…It has been shown that CCNA2 can be a key target for the treatment of lung adenocarcinoma, and abnormal expression of CCNA2 plays a critical role in the development of lung adenocarcinoma. [ 37 ] In addition, it has been shown that CCNA2 has a protective effect on innate immune responses and helps to reduce pathogen-induced inflammation and apoptosis, while CCNA2 is also critical for the regulation of immune-related gene expression. [ 38 ] CCNB1, a member of the G2/mitotic-specific cyclin B1 family, controls the transition from G2 to M phase, is expressed in G2 phase and degraded in M phase.…”

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

“…DPP4 inhibitors are commonly used to treat type 2 diabetes. Interestingly, many studies have shown that some DPP4 inhibitors (such as: selegiline and emetine) may have a therapeutic effect on neocoronary, but clinical trials are still needed to confirm their effects ( Mikhael et al, 2022 ; Zhang et al, 2022 ). In addition, many data show that diabetes is also a factor in causing severe symptoms of COVID-19 ( Zhou F. et al, 2020 ; Godeau et al, 2021 ).…”

Correction: Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses

“…Following publication of the original article [ 1 ], the authors identified a production error. Figure 8 was not correctly processed by the publisher.…”