The discovery of angiotensin-converting enzyme 2 (ACE2) has emerged as an crucial breakthrough twenty years ago, which has intensely improved our understanding of the renin–angiotensin system (RAS). Enzyme ACE is the key for functioning of classical RAS and is considered highly important in the regulation of blood pressure and fluid homeostasis. 

Currently, it has been recognised that the protective RAS regulated by ACE2 counterbalances many of the harmful effects of the classical RAS. Experimental model studies have shown that modulating of protective RAS can significantly modify various diseases including liver disease. Similarly, a study conducted in experimental model with liver fibrosis revealed that liver-specific overexpression of ACE2 was significantly efficacious in antagonising liver injury and fibrosis progression. However, regardless of its highly shielding role in pathogenesis of disease, ACE2 has been targeted by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans. COVID-19, a life-threatening disease has severe implications, especially in elderly or people with comorbidities. Owing to the fact that unexpectedly high number of individuals are affected with COVID-19 globally, there is an imperative need to warrant the discovery of novel therapeutics that can target the interaction between the SARS-CoV-2 spike protein and ACE2. Information regarding the role of ACE2 in physiology, pathobiology and as a cellular receptor for SARS-CoV-2 infection aids in the development of potential new treatment approaches that can prevent SARS-CoV-2 infection related tissue injury. 

Source: Warner FJ, Rajapaksha H, Shackel N, Herath CB. ACE2: from protection of liver disease to propagation of COVID-19. Clin Sci (Lond). 2020 Dec 11;134(23):3137-3158.