Avaliação dos efeitos de losartan e maleato de enalapril em células VERO infectadas com SARS-CoV-2

Abstract

Since its emergence, the COVID-19 pandemic has led to significant challenges to global healthcare systems, particularly impacting individuals with pre-existing conditions, such as hypertension. For this reason, the safety and influence of antihypertensive treatments during the course of the disease have been questioned by the scientific community. In this study, we investigated whether treatment with the antihypertensive drugs losartan or enalapril maleate, respectively an angiotensin receptor blocker (ARB) and an angiotensin-converting enzyme inhibitor (ACEi), in cells permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has any effect on virus replication, cell death, and biomarkers expression. The results revealed that losartan substantially reduced the levels of SARS-CoV-2 nucleocapsid RNA to nearly undetectable levels, while enalapril maleate did not demonstrate a significant effect. In response to the viral infection, the expression of IL-18, p53, p21, and p62 increased compared to untreated and uninfected cells. Notably, IL-6 expression was increased by both infection and treatments. A comparison between infected cells treated with losartan or enalapril maleate highlighted the presence of distinct profiles in the expression of IL-6, p53, p21, and p62. Therefore, there is evidence that these compounds, ACEi/ARB, modulate renal cells differently in face of SARS-CoV-2 infection, and this influence appears to alter both quantitatively and qualitatively in the modulation of metabolic and signal transduction pathways. However, it is still essential to conduct further research to understand the impact of antihypertensive medications on the progression of COVID-19 in different cell types, to elucidate how the mechanisms influenced by these medications affect patient outcomes.