Drugs acting on the renin-angiotensin system and SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global Coronavirus 2019 (COVID-19) pandemic, resulting in thousands of deaths worldwide and representing a health challenge with few precedents in human history. Angiotensin-converting enzyme 2 (ACE-2) facilitates the access of SARS-CoV-2 to cells. Therapeutic agents acting on the renin-angiotensin system (RAS) might be able to modulate the concentration of ACE-2 and the various components of the system. Here, we discuss current pharmacological, molecular, and clinical evidence to investigate whether drugs acting on RAS with modulation of the ACE-2 concentration have added value in combating SARS-CoV-2 infection. We also highlight the possible deleterious action of the ACE/Ang-II/AT-1r axis and possible beneficial role of the ACE-2/Ang 1-7/MasR axis in acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2, discussing the possibility of addressing the various RAS components with drug treatments to improve clinical outcomes.

Figure 1

The renin–angiotensin system (RAS). Vasodilatory, anti-inflammatory, and antifibrotic effects mediated by stimulation of the AT2 (AT2R) and Mas receptors (MasR) could be of clinical benefit during the most severe stages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the vasoconstrictory, proinflammatory, and profibrotic effects mediated by stimulation of AT1-r could increase lung damage.

Figure 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates cells by binding of the peak viral protein (spike; S) to angiotensin-converting enzyme 2 (ACE-2). ACE-2 converts angiotensin (Ang)-II to Ang 1–7. The latter have opposite biological actions to Ang-II (i.e., antifibrotic, antioxidant, and antihypertrophic effects) through stimulation of Mas receptor (MasR).