Unraveling the relevance of SARS-Cov-2 infection and ferroptosis within the heart of COVID-19 patients

Alizadeh Saghati et al., Heliyon, doi:10.1016/j.heliyon.2024.e36567, Sep 2024
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In silico study showing that ferroptosis-related genes are significantly altered in COVID-19 patients' hearts and identifying potential therapeutic compounds including famotidine, pyrvinium, astemizole, and thioridazine.
Alizadeh Saghati et al., 30 Sep 2024, China, peer-reviewed, 5 authors. Contact: m_talkhabi@sbu.ac.ir.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Unraveling the relevance of SARS-Cov-2 infection and ferroptosis within the heart of COVID-19 patients
Amin Alizadeh Saghati, Zahra Sharifi, Mehdi Hatamikhah, Marieh Salimi, Mahmood Talkhabi
Heliyon, doi:10.1016/j.heliyon.2024.e36567
Background: The coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a huge mortality rate and imposed significant costs on the health system, causing severe damage to the cells of different organs such as the heart. However, the exact details and mechanisms behind this damage are not clarified. Therefore, we aimed to identify the cell and molecular mechanism behind the heart damage caused by SARS-Cov-2 infection. Methods: RNA-seq data for COVID-19 patients' hearts was analyzed to obtain differentially expressed genes (DEGs) and differentially expressed ferroptosis-related genes (DEFRGs). Then, DEFRGs were used for analyzing GO and KEGG enrichment, and perdition of metabolites and drugs. we also constructed a PPI network and identified hub genes and functional modules for the DEFRGs. Subsequently, the hub genes were validated using two independent RNA-seq datasets. Finally, the miRNA-gene interaction networks were predicted in addition to a miRNA-TF coregulatory network, and important miRNAs and transcription factors (TFs) were highlighted. Findings: We found ferroptosis transcriptomic alterations within the hearts of COVID-19 patients. The enrichment analyses suggested the involvement of DEFRGs in the citrate cycle pathway, ferroptosis, carbon metabolism, amino acid biosynthesis, and response to oxidative stress. IL6, CDH1, AR, EGR1, SIRT3, GPT2, VDR, PCK2, VDR, and MUC1 were identified as the ferroptosisrelated hub genes. The important miRNAs and TFs were miR-124-3P, miR-26b-5p, miR-183-5p, miR-34a-5p and miR-155-5p; EGR1, AR, IL6, HNF4A, SRC, EZH2, PPARA, and VDR. Conclusion: These results provide a useful context and a cellular snapshot of how ferroptosis affects cardiomyocytes (CMs) in COVID-19 patients' hearts. Besides, suppressing ferroptosis seems to be a beneficial therapeutic approach to mitigate heart damage in COVID-19.
(caption on next page) A. Alizadeh Saghati et al. Heliyon 10 (2024) e36567 CRediT authorship contribution statement Amin Alizadeh Saghati: Writingoriginal draft, Investigation, Formal analysis. Zahra Sharifi: Writingreview & editing, Writingoriginal draft, Formal analysis, Data curation. Mehdi Hatamikhah: Writingoriginal draft. Marieh Salimi: Writingoriginal draft, Methodology. Mahmood Talkhabi: Supervision. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e36567 . A. Alizadeh Saghati et al. Heliyon 10 (2024) e36567
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