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.

• Authors: Kun Zhang, Ke Wang, Chaoguo Zhang, Xiuli Teng, Dan Li, Mingwei Chen
• Journal: BMC cancer (BMC Cancer) Vol. 22 Issue 1 Pg. 687 (Jun 22 2022) ISSN: 1471-2407 [Electronic] England
• PMID: 35733175 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• DNA-Binding Proteins
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Transcription Factors
• ZIC5 protein, human
• Emetine

Topics

• Adenocarcinoma of Lung (complications, drug therapy)
• Computational Biology
• DNA-Binding Proteins (genetics)
• Emetine (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (complications, drug therapy)
• Molecular Docking Simulation
• SARS-CoV-2 (drug effects)
• Serotonin Plasma Membrane Transport Proteins (genetics, metabolism)
• Transcription Factors (genetics)
• COVID-19 Drug Treatment