| Autor: |
Magda M. F. Ismail, Rehab R. El-Awady, Amal M. Farrag, Sara H. Mahmoud, Noura M. Abo Shama, Ahmed Mostafa, Mohamed A. Ali, Mohammed H. Rashed, Iman H. Ibrahim |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Genetic Engineering and Biotechnology, Vol 21, Iss 1, Pp 1-10 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2090-5920 |
| DOI: |
10.1186/s43141-023-00520-x |
| Popis: |
Abstract Background SARS-CoV-2 infection involves disturbing multiple molecular pathways related to immunity and cellular functions. PIM1 is a serine/threonine-protein kinase found to be involved in the pathogenesis of several viral infections. One PIM1 substrate, Myc, was reported to interact with TMPRSS2, which is crucial for SARS-CoV-2 cell entry. PIM1 inhibitors were reported to have antiviral activity through multiple mechanisms related to immunity and proliferation. This study aimed to evaluate the antiviral activity of 2-pyridone PIM1 inhibitor against SARS-CoV-2 and its potential role in hindering the progression of COVID-19. It also aimed to assess PIM1 inhibitor’s effect on the expression of several genes of Notch signaling and Wnt pathways. In vitro study was conducted on Vero-E6 cells infected by SARS-CoV-2 “NRC-03-nhCoV” virus. Protein–protein interaction of the study genes was assessed to evaluate their relation to cell proliferation and immunity. The effect of 2-pyridone PIM1 inhibitor treatment on viral load and mRNA expression of target genes was assessed at three time points. Results Treatment with 2-pyridone PIM1 inhibitor showed potential antiviral activity against SARS-CoV-2 (IC50 of 37.255 µg/ml), significantly lowering the viral load. Functional enrichments of the studied genes include negative regulation of growth rate, several biological processes involved in cell proliferation, and Interleukin-4 production, with interleukin-6 as a predicted functional partner. These results suggest an interplay between study genes with relation to cell proliferation and immunity. Following in vitro SARS-CoV-2 infection, Notch pathway genes, CTNNB1, SUMO1, and TDG, were found to be overexpressed compared to uninfected cells. Treatment with 2-pyridone PIM1 inhibitor significantly lowers the expression levels of study genes, restoring Notch1 and BCL9 to the control level while decreasing Notch2 and CTNNB1 below control levels. Conclusion 2-pyridone PIM1 inhibitor could hinder cellular entry of SARS-CoV-2 and modulate several pathways implicated in immunity, suggesting a potential benefit in the development of anti-SARS-CoV-2 therapeutic approach. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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