Effect of Common Medications on the Expression of SARS‐CoV‐2 Entry Receptors in Kidney Tissue

Abstract

Besides the respiratory system, severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS‐CoV‐2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS‐CoV‐2 receptor, angiotensin‐converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin‐angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS‐CoV‐2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2.

Endothelial cells and SARS-CoV-2: An intimate relationship

“…It is known that several drugs, including chemotherapeutics such as cisplatin, modulate ACE2 levels in cells [ 124 ]. In addition, trials are currently evaluating the action of the chemotherapeutic anti-VEGF bevacizumab on SARS-CoV-2 patients (NCT04275414) [ 108 ].…”

Association of ACE inhibitors and angiotensin type II blockers with ACE2 overexpression in COVID-19 comorbidities: A pathway-based analytical study

“…The therapeutic application of captopril in treating hypertension and cardiovascular comorbidities exhibited positive clinical outcomes. Similarly, Enalapril a known ACEi was reported to increase ACE2 expression in the kidney tissues whereas no such significant fold change was observed in TMPRSS2 mRNA expression ( Abuohashish et al 2017 ; Saheb et al 2020 ). Chappell and his group has reported increased expression of ACE2 mRNA, while optimum reduction in angiotensin II (plasma) expression upon treating the cardiac cells with lisinopril and losartan ( Ferrario et al 2005 ).…”

SARS-CoV-2 Switches ‘on’ MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression

“…Spleen tissue from DUSP1-deficient mice (GSE3565) (Hammer et al, 2006) and bone marrow-derived eosinophils from DUSP5-deficient mice (GSE62999). Datasets of medication treatments were extracted from the TG-GATEs database and the high and middle doses were used, as previously described (Sharif-Askari et al, 2020a;Sharif-Askari et al, 2020b;Sharif-Askari et al, 2020c). The data for chloroquine treatment was extracted from the GSE30351 dataset.…”