El texto completo de este artículo está disponible en PDF.
Candesartan downregulates expression of many glutamate upregulated genes in cultured neurons.
Glutamate upregulated genes in neurons positively correlate with COVID-19 upregulated genes.
Candesartan gene downregulation negatively correlates with COVID-19 upregulated genes.
Candesartan downregulates genes involved in the COVID-19 cytokine storm.
Angiotensin receptor blockers (ARBs) reducing inflammation and protecting lung and brain function, could be of therapeutic efficacy in COVID-19 patients.
Using GSEA, we compared our previous transcriptome analysis of neurons injured by glutamate and treated with the ARB Candesartan (GSE67036) with transcriptional signatures from SARS-CoV-2 infected primary human bronchial epithelial cells (NHBE) and lung postmortem (GSE147507), PBMC and BALF samples (CRA002390) from COVID-19 patients.
Hundreds of genes upregulated in SARS-CoV-2/COVID-19 transcriptomes were similarly upregulated by glutamate and normalized by Candesartan. Gene Ontology analysis revealed expression profiles with greatest significance and enrichment, including proinflammatory cytokine and chemokine activity, the NF-kappa B complex, alterations in innate and adaptive immunity, with many genes participating in the COVID-19 cytokine storm.
There are similar injury mechanisms in SARS-CoV-2 infection and neuronal injury, equally reduced by ARB treatment. This supports the hypothesis of a therapeutic role for ARBs, ameliorating the COVID-19 cytokine storm.El texto completo de este artículo está disponible en PDF.
Keywords : COVID-19, SARS-CoV-2, Immunity, Inflammation, NF-κB, Cytokine storm, Interferon, Angiotensin receptor blockers