Renin-Angiotensin System Inhibitors in COVID-19: Current Concepts

Figure 2

The interplay between RAS (renin-angiotensin system) and COVID-19 (coronavirus disease 2019). SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) enters the host epithelial cell after its spike protein’s receptor-binding domain binds to the membrane-bound ACE-2 (angiotensin-converting enzyme-2) receptor. The cellular entry is followed by endocytosis and further viral replication and subsequent release. SARS-CoV-2, after entry inside the cell, causes downregulation of further ACE-2 expression. ACE-2 is responsible for the conversion of Ang (angiotensin) II to Ang (1–7) and Ang-I to inactive Ang (1–9). The downregulation of ACE-2 results in an unopposed action of Ang-II through its AT1 (angiotensin II type 1) receptor. ACE-I (angiotensin-converting enzyme inhibitor) and ARB (angiotensin receptor blocker) oppose Ang-II’s action by blocking its synthesis and receptor, respectively. ACE-I/ARB may also cause overexpression of the soluble form of ACE-2, which intercepts the binding of SARS-CoV-2 with membrane-bound ACE-2, thus inhibiting the viral entry into the host cell.