Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Metformin*/pharmacology ; Metformin*/therapeutic use ; Glucose*/metabolism ; TOR Serine-Threonine Kinases*/metabolism ; COVID-19*/metabolism ; COVID-19*/virology ; Lung Neoplasms*/drug therapy ; Lung Neoplasms*/metabolism ; Cell Proliferation*/drug effects ; PTEN Phosphohydrolase*/metabolism ; Adenocarcinoma of Lung*/drug therapy ; Adenocarcinoma of Lung*/metabolism ; Adenocarcinoma of Lung*/pathology ; Signal Transduction*/drug effects ; COVID-19 Drug Treatment*; Humans ; A549 Cells ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Energy Metabolism/drug effects

Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD ⁺ /NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.
(© 2024. The Author(s).)

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20220596 Hebei Health hScientific Research Foundation Project

Keywords: Bioinformatics; COVID-19; Glucose metabolism; LUAD; Metformin

9100L32L2N (Metformin)
IY9XDZ35W2 (Glucose)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 3.1.3.67 (PTEN Phosphohydrolase)
EC 2.7.1.1 (MTOR protein, human)
EC 3.1.3.67 (PTEN protein, human)

Date Created: 20240529 Date Completed: 20240529 Latest Revision: 20240601

20240601

PMC11137110

10.1038/s41598-024-63081-0

38811809