Angiotensin-converting enzyme type 2 as a molecular mediator for infection of cells with sars-cov and sars-cov-2 viruses

Penetration of coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), the cause of the COVID-19 pandemic, into cells requires interaction of the surface spike S protein of the virus with extracellular domain of the membrane-bound form of angiotensin-converting enzyme type 2 (ACE2) This enzyme, the key component of the renin-angiotensin system, is responsible for the synthesis of angiotensin-(1-7), which has vasodilator and autoimmune properties, from angiotensin II, a powerful vasoconstrictor, whose synthesis is catalyzed by angiotensin-converting enzyme (ACE), a functional antagonist of ACE2 After site-specific hydrolysis by transmembrane serine protease TMPRSS2 in infected cells, viral S protein specifically binds ACE2, which is the trigger for internalization of the virus into cells by endocytosis Suppression of this process with drugs inhibiting TMPRSS2 protease and impairing the interaction of S protein with ACE2 prevents infection and is therefore a potential approach to the treatment and prophylaxis of COVID-19 This mechanism of penetration into cells is also used by SARS-CoV virus, the pathogen of atypical pneumonia, which is related to SARS-CoV-2 Treatment of patients with arterial hypertension and diabetes mellitus using ACE inhibitors and angiotensin receptor blockers, statins, and various antidiabetic drugs generally increases the expression and activity of ACE2, which increases the risk of infection with SARS-CoV-2 and worsens the outcome of disease During the process of infection, the virus forms a complex with ACE2 and decreases the quantity of ACE2 on the cell surface, impairing ACE2-dependent physiological processes, and this is one of the causes of acute respiratory distress syndrome and heart failure in COVID-19 patients The present review analyzes the functional role of ACE2 in the infection of cells by SARS-CoV-2 and SARS-CoV, and the molecular mechanisms of this process and its pathophysiological consequences are discussed (PsycInfo Database Record (c) 2021 APA, all rights reserved)