Researchers have discovered that two commonly prescribed antihypertensive medications, losartan and enalapril maleate, can have markedly different effects on SARS-CoV-2 infection in Vero cells, a model system for studying the virus. While losartan significantly reduced the levels of SARS-CoV-2 RNA, enalapril maleate did not show a significant impact. This finding suggests that these drugs may interfere with the cellular processes hijacked by the virus, potentially offering new avenues for COVID-19 treatment. The study also reveals distinct profiles in the expression of genes involved in cell cycle regulation, inflammation, and autophagy, highlighting the complex interplay between these antihypertensive medications and the SARS-CoV-2 infection.
Unraveling the Mysteries of COVID-19 and Hypertension
The COVID-19 pandemic caused by the SARS-CoV-2 virus has posed significant challenges to global healthcare systems, particularly for individuals with pre-existing conditions like hypertension. Understanding the relationship between COVID-19 and hypertension has become a crucial area of research, as these patients often experience more severe complications.
SARS-CoV-2 utilizes the system’>renin-angiotensin system (RAS), which plays a vital role in regulating blood pressure, inflammation, and other physiological processes. This connection between SARS-CoV-2 and the RAS has raised concerns about the potential impact of commonly prescribed antihypertensive medications, such as angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEis), on COVID-19 patients.
Investigating the Differential Effects of Losartan and Enalapril Maleate
In a recent study published in the journal Scientific Reports, researchers set out to explore the impact of the ARB losartan and the ACEi enalapril maleate on SARS-CoV-2-infected Vero cells, a widely used model system for studying the virus.
The researchers first evaluated the cytotoxicity of these medications on Vero cells, and the results showed that both losartan and enalapril maleate were non-toxic to the cells, even at the highest concentrations tested.
Next, the team assessed the antiviral activity of these drugs by measuring the levels of SARS-CoV-2 RNA in infected cells. Interestingly, they found that losartan at the highest concentration (1000 μM) significantly reduced the levels of the viral nucleocapsid RNA to nearly undetectable levels, while enalapril maleate did not demonstrate a significant effect.
Uncovering the Molecular Mechanisms
To better understand the underlying mechanisms, the researchers examined the expression of several genes involved in cellular processes, such as inflammation, cell cycle regulation, and autophagy.
The analysis revealed that SARS-CoV-2 infection led to an upregulation of the IL-6 and IL-18 genes, which encode pro-inflammatory cytokines. While both losartan and enalapril maleate treatments increased IL-6 expression in infected cells, the team observed a distinct profile for each drug. Notably, infected cells treated with losartan did not show a significant difference in IL-6 levels compared to infected-untreated cells, suggesting that losartan may have a dampening effect on this inflammatory response.
Regarding cell cycle regulation, the researchers found that SARS-CoV-2 infection increased the expression of the p53 and p21 genes, which play crucial roles in cell cycle arrest and DNA damage response. Interestingly, infected cells treated with the higher concentration of enalapril maleate (1000 μM) exhibited a further increase in p53 and p21 expression, potentially indicating a more robust cellular response to the viral infection.
The study also investigated the expression of the p62 gene, which is involved in the autophagy pathway. Viral infection led to an upregulation of p62, but both losartan and enalapril maleate treatments were able to reduce its expression compared to infected-untreated cells, suggesting a potential modulation of the autophagy process.
Implications and Future Directions
The findings from this study suggest that losartan and enalapril maleate, two commonly prescribed antihypertensive medications, can differentially influence the cellular response to SARS-CoV-2 infection. While losartan appears to significantly inhibit viral replication, enalapril maleate may trigger a more robust cellular defense mechanism involving p53 and p21 upregulation.
These insights could have important implications for the management of COVID-19 in hypertensive patients. The ability of these drugs to modulate key cellular pathways, such as inflammation, cell cycle regulation, and autophagy, may provide new avenues for targeted therapeutic interventions against SARS-CoV-2.
However, it’s important to note that this study was conducted in a cell culture model, and further research is needed to understand the real-world implications of these findings. Additional in-depth studies, including clinical trials, will be necessary to fully elucidate the potential protective or therapeutic effects of these antihypertensive medications in COVID-19 patients.
As the scientific community continues to unravel the complex interplay between COVID-19, hypertension, and the RAS, this study highlights the importance of exploring the nuanced and diverse ways in which common medications can impact the course of viral infections. By understanding these mechanisms, researchers may unlock new strategies to combat the devastating effects of the COVID-19 pandemic.
Author credit: This article is based on research by Julia H. Majolo, João I. B. Gonçalves, Renata P. Souza, Laura C. González, Nathalia Sperotto, Maiele D. Silveira, Sílvia D. Oliveira, Cristiano V. Bizarro, Pablo Machado, Luiz A. Basso, Ana P. D. Souza, Jarbas R. Oliveira, Carlos A. S. Ferreira.
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