The renin–angiotensin system is a central mechanism for blood pressure regulation through a diverse system of hormones and receptors. Angiotensin-converting enzyme (ACE) is an ectoenzyme that plays a role in the generation of Ang II by catalyzing the extracellular conversion of the decapeptide Ang I. Moreover, ACE degrades active bradykinin (BK), which play an important role in the control of blood pressure. ACE2 is an ACE homolog that was discovered in 2000 when two independent research groups cloned homologous ACE that could convert Ang I to Ang (1–9). Sequence analysis suggests that ACE and ACE2 exhibit 42% amino acid homology and ACE2 has evolved through gene duplication¹.

ACE2 consist of N-terminal peptidase domain with seven potential N-linked glycosylation sites that bears the characteristic HEXXH motif of M2 metalloproteases. It is mainly expressed in the small intestine, testis, kidneys, heart, thyroid and adipose tissue and in the lungs. ACE 2 has a protective role in the cardiovascular system and in alveolar epithelial cells. In the lungs ACE2 has numerous physiological functions, most of which are protective against lung injury².

ACE 2 was identified as the receptor for highly pathogenic SARS (severe acute respiratory syndrome) coronavirus including the SARS-CoV-2 that cause the coronavirus disease 2019 (COVID-19) global pandemic. SARS virus binding downregulates the cellular expression of ACE2, and the binding induces clathrin-dependent internalization of virus/receptor (SARS/ACE2) complex. Not only has ACE2 facilitated the invasion of SARS virus for rapid replication, but also ACE2 is depleted from the cell membrane and therefore the damaging effects of Ang II are enhanced, resulting in acute deterioration of lung tissues³.