the Differential Effects of Antihypertensive Drugs on SARS-CoV-2 Infection

Unraveling the Mysteries of SARS-CoV-2 and Hypertension

The COVID-19 pandemic has posed significant challenges to global healthcare systems, particularly impacting individuals with pre-existing conditions like hypertension. SARS-CoV-2, the virus that causes COVID-19, uses the system’>renin-angiotensin system (RAS), which plays a crucial role in regulating blood pressure, is closely linked to the ACE2 receptor.

Antihypertensive medications, such as ARBs and ACEis, are commonly prescribed to manage hypertension. With the outbreak of the COVID-19 pandemic, concerns arose regarding the potential impact of these drugs on patient outcomes. The current study aimed to investigate the influence of the ARB losartan and the ACEi enalapril maleate on SARS-CoV-2 infection and cellular responses in assay’>MTT assay, which measures cell viability. The findings revealed that both compounds were non-toxic to the cells, even at the highest concentrations tested.

Next, the researchers investigated the antiviral activity of these drugs by measuring the levels of SARS-CoV-2 viral RNA in infected cells. Interestingly, they found that losartan at the highest concentration (1000 µM) significantly reduced the levels of the viral nucleocapsid (N) gene, indicating a potent antiviral effect. In contrast, enalapril maleate did not demonstrate a significant impact on viral RNA levels.

Uncovering the Differential Cellular Responses

To further understand the mechanisms underlying the observed effects, the researchers analyzed the expression of several genes related to cellular processes, such as inflammation, cell cycle regulation, and autophagy.

Inflammatory Response: The study revealed that SARS-CoV-2 infection led to an upregulation of interleukin-6 (IL-6) and interleukin-18 (IL-18) gene expression. Interestingly, while both losartan and enalapril maleate treatments increased IL-6 levels in infected cells, only enalapril maleate showed a significant upregulation of IL-18 expression. This suggests that the two drugs may differentially modulate the inflammatory response to SARS-CoV-2 infection.

Cell Cycle Regulation: The study also examined the expression of genes involved in cell cycle regulation, such as p53, 1’>p62. The findings indicate that SARS-CoV-2 infection upregulated the expression of these genes, which play crucial roles in cell cycle arrest, DNA repair, and autophagy. Notably, the researchers observed distinct profiles in the expression of these genes between losartan- and enalapril maleate-treated infected cells, suggesting that the two drugs may differentially influence cellular signaling pathways.

Implications and Future Directions

The data from this study provide valuable insights into the potential mechanisms by which antihypertensive medications, specifically losartan and enalapril maleate, may influence the course of COVID-19 in patients with hypertension. The significant reduction in SARS-CoV-2 viral RNA levels observed with losartan treatment suggests that this ARB may have a direct antiviral effect, potentially by interfering with the virus’s entry or replication within host cells.

Moreover, the distinct profiles in the expression of genes related to inflammation, cell cycle regulation, and autophagy highlight the complex interplay between these antihypertensive drugs and the host’s cellular response to SARS-CoV-2 infection. These findings may have important implications for understanding the variable clinical outcomes observed in COVID-19 patients with hypertension who are treated with different classes of antihypertensive medications.

Advancing the Understanding of COVID-19 and Hypertension

While the current study provides valuable insights, further research is needed to fully elucidate the mechanisms by which antihypertensive medications influence the progression of COVID-19. Investigating the effects of these drugs in different cell types and in vivo models will be crucial to gain a comprehensive understanding of their impact on SARS-CoV-2 infection and the associated host responses.

Ultimately, the findings from this study contribute to the growing body of evidence suggesting that the chronic use of certain antihypertensive medications may play a role in modulating the clinical outcomes of COVID-19 in patients with hypertension. This knowledge could pave the way for more personalized treatment approaches and improved management strategies for this vulnerable patient population.

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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