Lithium Chloride Modulates Inflammatory and Apoptotic Responses in Lung Adenocarcinoma Cells Challenged with SARS-CoV-2 S1-His Protein Recombinant

Background : In 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began the COVID-19 pandemic, resulting in millions of deaths worldwide. Lung cancer patients infected with SARS-CoV-2 were found to be particularly vulnerable to severe and fatal outcomes. This study aimed to explore whether lithium chloride (LiCl), a drug commonly used to treat mental disorders, could serve as a potential inhibitor of inflammatory markers in lung adenocarcinoma cells exposed to the SARS-CoV-2 glycoprotein. Methods : The in vitro cytotoxic effects of lithium chloride were assessed using the Muse ^® Ki67 proliferation assay, cell death, cell cycle analysis. Nitric oxide measurement assay, oxidative stress assay, IL-6, NF-κB and human inflammation antibody array membrane were performed to evaluate the inflammation parameters after LiCl treatments. Results : The spike protein stimulated ROS and NO production, and treatment with low concentrations of LiCl reduced the percentage of oxidative stress. Cell death assay showed that the lithium chloride reduced the late apoptotic effects of the spike protein. Cell cycle analysis showed that spike protein increased the S phase population of A549 cells and treatment with LiCl increased the G2/M populations. LiCl and the spike protein individually increased IL-6 and NF-κB expression however, co-treatment with the spike protein reduced the expression levels. The spike protein had strong positive spots for 26 targets and co-treatment with LiCl reduced their intensity. Conclusion : These findings suggest that LiCl is a promising candidate for targeting the inflammatory pathway triggered by the SARS-CoV-2 spike protein. Additionally, LiCl promotes early apoptosis and induces G2/M phase cell cycle arrest in A549 cells exposed to the SARS-CoV-2 spike protein. This study presents a potential therapeutic approach for utilizing LiCl in the management of SARS-CoV-2 infection in lung cancer patients.