Interactions between ibuprofen, ACE2, renin‐angiotensin system, and spike protein in the lung. Implications for COVID‐19

Abstract

The renin-angiotensin system (RAS) is constituted by two opposite arms that must be perfectly balanced. First, a RAS oxidative pro-inflammatory arm/axis (in red) mainly constituted by angiotensin II (the most effective RAS peptide) and its type I receptor (AT1R). Second, an anti-oxidative anti-inflammatory arm/axis (in green) constituted by Angiotensin II/AT2R, and particularly Angiotensin 1-7 /Mas receptors (MASR). Angiotensin II is synthetized by two enzymes, prorenin/renin and angiotensin converting enzyme (ACE), sequentially acting on the precursor protein angiotensinogen and angiotensin I, respectively. Angiotensin converting enzyme 2 (ACE2) is a key component for the RAS balance, as ACE2 (with the aid of additional peptidases such as Neprilysin, NEP) converts peptides of the pro-inflammatory arm (i.e. Angiotensin I and particularly Angiotensin II) into peptides of the anti-inflammatory arm (i.e. Angiotensin 1-9, and particularly Angiotensin 1-7).