Angiotensin-converting enzyme 2 (ACE2)

• ACE2 gene encodes the angiotensin-converting enzyme-2

• ACE2 acts as a cell surface receptor for Human coronavirus. Normally, the ACE2 receptor plays an important role in regulating the body’s blood pressure and fluid balance.

• The surface expression of the ACE2 protein occurs on lung alveolar epithelial cells and enterocytes of the small intestine. As such, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine.

• The coronavirus gains entry into a cell via exploiting ACE2 and type II transmembrane serine proteases (TMPRSS2) see below.

• Basically, the coronavirus S (spike) protein of COVID-19 binds to ACE2 with high affinity.

• Binding of the coronavirus S protein to ACE2 triggers a conformational change in the S protein of the coronavirus, allowing for proteolytic digestion by host cell proteases (TMPRSS2), thereby facilitating COVID-19 virus to human cell membrane fusions, and subsequent inflammatory immune system response (IL-6, and IL1B) see below.

• NOTE: Although ACE inhibitors and ARBs are useful drugs in the treatment of high blood pressure, CAD and diabetes, (used to reduce blood pressure, decrease risk of progressive kidney disease, and decrease risk of dying if one is at high cardiovascular risk), there are ongoing questions as to whether taking ACE inhibitors or ARBs increase or decrease ones susceptibility to the more severe symptoms of COVID-19.

• A March 2020 article in the Lancet, entitled, Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?, suggested that because the expression of ACE2 is substantially increased in patients with diabetes, heart disease, etc., who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs), “…they are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs”

• ACE2 has binding sites for Zinc and Chloride

Associated studies:
http://www.nephjc.com/news/covidace2
https://onlinelibrary.wiley.com/doi/full/10.1002/path.1570
https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(20)30116-8.pdf