Activation of Ang-(1-7)/Mas Receptor Is a Possible Strategy to Treat Coronavirus (SARS-CoV-2) Infection.

Giselle Santos Magalhaes,Daisy Motta-Santos,Maria Jose Campagnole-Santos,Robson A Souza Santos,Maria Da Gloria Rodrigues-Machado

doi:10.3389/fphys.2020.00730

Abstract

The renin-angiotensin system is involved in the pathophysiology of inflammatory diseases through an increase in angiotensin converting enzyme (ACE)/angiotensin (Ang) II/AT1 receptor axis activity. It has been shown that ACE activity is increased in acute respiratory distress syndrome and there is a strong correlation between the level of ACE activity and the degree of lung injury. SARS-CoV-2, the new coronavirus that causes COVID-19, similar to other coronaviruses, was recently shown to use ACE2 as a receptor to get into host cells. However, it has been reported that most of the treatments that stimulates the ACE2/Ang-(1-7)/Mas axis induces beneficial effects, such as, antihypertensive, anti-inflammatory, anti-proliferative, anti-thrombotic and anti-fibrotic. Here we discussed the potential of activation of Ang-(1-7)/Mas pathway as strategy to treat COVID-19.

Highlights

Coronavirus disease (COVID)-19 is developed from the virus entering the host cells, initially in the airways, mouth, eyes, and lungs
There is mounting evidence that the protective arm of the renin-angiotensin system (RAS) plays a central role in many functions linked to this system
The heart, lungs, brain, and blood vessels are among the organs in which the ACE2 product, Ang-(1-7) exerts actions that include cardioprotection, improvement of endothelial function, beneficial central actions, anti-thrombogenic, anti-inflammatory, and pro-resolving effects (Figure 1; Santos et al, 2018)

Summary

INTRODUCTION

Coronavirus disease (COVID)-19 is developed from the virus entering the host cells, initially in the airways, mouth, eyes, and lungs. The effects of these treatments may be partially related to an increase in Ang-(1-7) levels in the lung (Kohara et al, 1993; Santos et al, 2018) In another example of chronic lung inflammation, such as asthma, treatment with Ang-(17) was shown to reduce eosinophils count in the lung, to reduce the production of inflammatory mediators, to decrease activation of signaling pathways related to the production of cytokines, chemokines, and survival of inflammatory cells (Magalhaes et al, 2015, 2018). We have observed similar results in a model of neutrophil-induced inflammation, arthritis (Barroso et al, 2017) In this condition, blocking the Mas receptor delayed natural resolution, emphasizing that the ACE2/Ang(1-7)/Mas axis plays an important physiological role in the FIGURE 1 | Schematic view of the consequences of COVID-19 on the renin-angiotensin system (RAS). The endothelium is rich in ACE2 and its removal from the cell membrane, as the virus enters the cell, reduces its enzymatic function at the vessel wall, generating RAS imbalance with the deleterious result of inflammation, fibrosis, and thrombosis

THE WAY FORWARD

AUTHOR CONTRIBUTIONS