The renin angiotensin system (RAS) involvement in SARS-CoV-2 infection

Rafael Franco1,2 and Gemma Navarro2,3

1 Department of Biochemistry and Molecular Biomedicine. School of Biology. Universidad de Barcelona. Barcelona. Spain; rfranco@ub.edu

2 Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED). Instituto de Salud Carlos III. Madrid. Spain.

3 Department of Biochemistry and Physiology. School of Pharmacy and Food Science. Universidad de Barcelona. Barcelona. Spain; g.navarro@ub.edu

COVID-19 pandemics is due to SARS-CoV-2 coronavirus, which uses the angiotensin converting enzyme 2 (ACE2) as main cell surface receptor. The link between ACE2 and coronaviruses of the SARS family was serendipitously discovered, and there are chances that SARS-CoV-2 disbalances the renin-angiotensin-system thus leading to aberrant production of cytokines, i.e. to cytokine storm. In fact, plasma IL-6 levels correlate with morbidity in COVID-19 patients, may be produced by macrophages and by lung cells, all of which express the components of the renin-angiotensin system (RAS).

ACE2, which converts angiotensin II into angiotensin 1-7, is a RAS component that has been widely characterized in kidney and is target of efficacious antihypertensive drugs. Apart from ACE2 and other enzymes processing renin/angiotensin, RAS components include receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs). Two of them, AT1 (AT1R) and AT2 (AT2R) share the endogenous ligand, angiotensin II, i.e. the substrate of ACE2. The receptor for angiotensin 1-7 is known as Mas receptor (MasR).

Here we present further evidence of the translational potential on COVID-19 of research on RAS. The physical and functional interactions of ACE2 with the RAS receptors are presented as well as the expression of enzyme-receptor complexes in the main target organ of SARS-CoV-2, the lung.