The renin-angiotensin system and specifically angiotensin-converting enzyme 2 as a potential therapeutic target in SARS-CoV-2 infections

Abstract

In March 2019, the global COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus began. The first cases of SARS-CoV-2 infection occurred in November 19 in Wuhan, China. Preventive measures taken have not prevented the rapid spread of the virus to countries around the world. To date, there are approximately 3 million deaths, and a massive worldwide vaccination campaign has recently begun. SARS-CoV-2 uses the ACE-2 protein as an intracellular carrier. ACE-2 is a key component of the renin-angiotensin system (RAS), a key regulator of cardiovascular function. Considering the key role of ACE-2 in COVID-19 infection, both as an entry receptor and as a protective role, especially for the respiratory tract, and considering the variations of ACE-2 during the phases of viral infection, it is clear the important role that pharmacological regulation of RAS and ACE-2 may take. In this article, we describe the importance of ACE-2 in COVID-19 infection, the pharmacological aspects of a modulation with RAS-modifying agents, new therapeutic strategies, trying to provide a deep understanding and explanation of the complex mechanisms underlying the relationship between the virus and ACE-2, providing opinions and personal hypotheses on the best strategies of therapeutic intervention.

The role of the brain renin-angiotensin system in Parkinson´s disease

“…ACE2 has been intensely studied over the last few years because ACE2 is the primary binding site for SARS-CoV-2 entry into host cells [ 40 , 41 ]. Many studies have suggested a major role of the tissue RAS in the pathophysiology and severity of COVID-19 [ 42 , 43 ], as viral binding reduces the ACE2 levels at the cell surface [ 44 ], which leads to a shift in the RAS balance toward inflammation and disease severity. This raised the dilemma of increasing ACE2 levels in tissues to inhibit the inflammatory responses or decreasing tissue ACE2 levels to inhibit viral entry and replication.…”

Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment

“…A considerable number of studies have suggested the major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 [ 4 , 5 , 6 , 7 , 8 ]. The link between RAS and COVID-19 is mainly related to the role of angiotensin-converting enzyme 2 (ACE2), a central component of the RAS, as the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells [ 9 , 10 ].…”

Plausible Positive Effects of Statins in COVID-19 Patient

“…SARS-CoV-2 enters cells through the ACE-2 entry receptor that is expressed in several tissues, the lung, heart, and liver [ 22 , 23 ]. The multisystem inflammation that is generated is responsible for organ damage and fibrotic tissue formation in the lung, heart, and liver [ 24 , 25 ].…”