[6][7][8] Both membrane bound and soluble ACE2 are integral parts of the renin–angiotensin–aldosterone system (RAAS) that exists to keep the body's blood pressure in check.

[12] This decrease in blood pressure makes the entire process a promising drug target for treating cardiovascular diseases.

mACE2 is a single-pass type I membrane protein, with its enzymatically active domain exposed on the surface of cells in the intestines and other tissues.

[21] As part of the renin–angiotensin–aldosterone system (RAAS) protective phase, soluble ACE2's (sACE2) important function is to act as a counterbalance to the angiotensin-converting enzyme (ACE).

[25][26][27] Research in mice has shown that ACE2 (whether it is the membrane bound version or soluble is inconclusive) is involved in regulation of the blood glucose level but its mechanism is yet to be confirmed.

[41] The receptor-binding domain (RBD) of spike protein, located on the virus’s surface, specifically attaches to human cell receptors.

[38] The binding of the SARS-CoV-2 virus through mACE2 receptors present in heart tissue may be responsible for direct viral injury leading to myocarditis.

[43] This entry process also requires priming of the S protein by the host serine protease TMPRSS2, the inhibition of which is under current investigation as a potential therapeutic.

[44][21] It has also been shown that disruption of S-protein glycosylation significantly impairs viral entry, indicating the importance of glycan-protein interactions in the process.

[48] Both ACE inhibitors and angiotensin II receptor blockers (ARBs) that are used to treat high blood pressure have been shown in rodent studies to upregulate mACE2 expression, possibly affecting the severity of coronavirus infections.

[49][50] However, a systematic review and meta-analysis published on July 11, 2012, found that "use of ACE inhibitors was associated with a significant 34% reduction in risk of pneumonia compared with controls."

The death rate was compared with 9.8% of hospitalized patients with hypertension not taking such drugs, suggesting that ACE inhibitors and ARBs are not harmful and may help against the coronavirus.

[53] However, multiple professional societies and regulatory bodies have recommended continuing standard ACE inhibitor and ARB therapy.

Moreover, those variants have shown a 37% reduction in expression of the protein and a remarkable protection from severe outcomes (respiratory failure and death).

[66] An in vitro study focused on the early stages of infection found that clinical-grade human recombinant soluble ACE2 (hrsACE2) reduced SARS-CoV-2 recovery from vero cells by a factor of 1,000–5,000.