Role of ARBs and ACEIs in the treatment of SARS-COV2

Abstract

The coronavirus 2 (SARS‐CoV‐2) induces severe acute respiratory distress syndrome (ARDS)via the coronavirus receptor angiotensin‐converting enzyme 2 (ACE2) in the host cell to facilitate entry into the lungs Over activation of the renin‐angiotensin system (RAS) and the down regulation of ACE2 expression are involved in SARS‐CoV induced lung injury. RAS is the main system that has a regulatory roleinmaintaining electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling in the body. Angiotensin II receptor blockers (ARBs) and Inhibitors (ACEIs) are vital medications that are widely used for the treatment of cardiovascular diseases (CVDs). The question which now arises is: It is possible to continue using either ARBs or ACEIsor both medications in patients with SARS-CoV2? Both ARBs and ACEIs can facilitate COVID-19 entry into the host cell due to increase expression of ACE2. On the other hand, ARBs have a greater potential to reduce downstream pathogenicity of the SARS-CoV2 via different cell signaling pathways including free radical generation, up regulation of NF-κB pathway, toll-like receptors (TLRs) and pro-apoptotic protein by blocking the renin–angiotensin system more severely compared to the effect of ACEIs. The current hypothesis is that ARBs can perform better therapeutically compared to ACEIs in respiratory disorders such as ARDS which is induced by viral infection especially since more than 40 % of angiotensin II can be synthesized by other enzymes such as chymase, cathepsin. ARBs treatment can increase the levels of both angiotensin II (Ang II) and the ACE2 enzyme making Ang II a target substrate for hydrolysis by ACE2 into Ang 1-7 which in turn exerts anti-inflammatory, anti-apoptotic and anti-oxidant activities. These effects are achieved by the binding of Ang 1-7 to both angiotensin-type 2 receptor (AT2) and receptor mas’ axis (Mas) and also by its ability to block Ang II/AT1 receptor-induced TLR4/MyD88 signaling thereby highlighting the potential therapeutic use of ARB sin preventing injury induced by COVID-19 virus. It is concluded that patients who are already on ARBs medications must continue to use them daily since ARBs have protective effects against COVID-19 virus. Moreover, ARB sexert their beneficial effects via their anti-inflammatory, anti-apoptotic, anti-oxidant and anti-fibrotic properties. On the other hand, those patients who are on ACEIs medications must change to other safe drugs since ACEIs can facilitate an increase in COVID-19 virus entry into the body as well as reducing levels and protecting effect of Ang 1-7.