Investigation of the effects of all-trans retinoic acid and 1,25-dihydroxy vitamin D3 on SARS-COV-2 target and mediator molecules

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a novel coronavirus and RNA virus that is the causative agent of severe acute respiratory disease (Covid-19). ACE2, TMPRSS2, TMPRSS11D and CD147 are proteins required for the activation, infection and transmission of SARS-CoV-2. ACE2 receptors are found in many tissues such as lungs, intestines, heart and kidneys. There is also an ACE2 receptor in endothelial cells. During SARS-CoV-2 infection, other intermediary molecules in the cells, especially ACE2, can determine the course of the disease. ATRA and vD3 are nuclear hormone receptors that exert their molecular effects through receptors located in the cell and can act at the gene level by regulating transcription in the cell nucleus. In our literature review, there was no study on the molecular expressions of ATRA and vD3 mediating the SARS-CoV-2 infection mechanism. In addition, patients with Covid-19 disease are given high doses of Vitamin D3 as a treatment in many clinics. In this study, we will analyze the expressions of cellular molecules associated with SARS-CoV-2 in endothelial cells where we will apply ATRA and vD3 as nuclear hormone receptor ligands. For this purpose, expression changes, cell proliferation and migration of target genes such as ACE2, TMPRSS2, TMPRSS11D, CD147, CD26, CYPA were investigated as a result of both ATRA and vD3 treatment in endothelial cells. These genes could be potential targets for elucidating the mechanism by which SARS-CoV-2 enters the target cell. In addition, analyses of different results in the expression of target genes will contribute to the literature on the effect of endothelial cells on the level of gene expression. In addition, ATRA suppressed migration and cell proliferation in endothelial cells. It also increased migration in vD3 endothelial cells and did not suppress or affect cell proliferation. In this respect, our findings will contribute to the elucidation of the mechanism of SARS-CoV-2 in endothelial cells and contribute to the literature in the treatment of COVID-19 disease.