What is ACE2?
ACE2 is an enzyme molecule that connects the inside of our cells to the outside via the cell membrane.
In normal physiology, another enzyme called ACE alters a chemical, Angiotensin I, and converts it into Angiotensin II, which causes blood vessels to constrict. The tightening of the blood vessels leads to an increase in blood pressure.
That’s when the ACE2 molecule comes in: to counteract the effects of ACE, causing blood vessels to dilate and lowering blood pressure.
These spikes on the surface of virus are called S1 proteins, and they are what binds to the ACE2 molecule on our cells.
The virus is then able to invade the cell by a process called endocytosis — where the cell membrane engulfs the virus and internalises it within a bubble called an endosome.
Once inside the cell, the virus interacts with the host cells’ genetic machinery, taking advantage of the existing structure to replicate extensively.
SARS-CoV-2, the virus behind COVID-19, has a high binding capacity for ACE2 — between 10 and 20 times more than the original SARS virus. This means it is much easier for SARS-CoV-2 to get into human cells compared to the original coronavirus, making it more infectious overall.
ACE2 and COVID-19
But there is still conflicting evidence on the precise role ACE2 plays in coronavirus infections.
In some cases, it can actually be of benefit: ACE2 has been shown to reduce injury to the lung tissue in cases of the original SARS virus in mice by doing its job and causing blood vessels to dilate.
ACE2 is a receptor on the surface of cells. It binds to the coronavirus and allows it to enter and infect healthy cells after it is has been modified by another protein on the surface of the cell, called TMPRSS2. High levels of ACE2 are present in the lungs and, therefore, it is thought to play a crucial role in the progression of lung disorders related to Covid-19.
ACE2 and the male death toll
It’s well established that COVID-19 affects men and women differently.
Men have higher levels of the angiotensin-converting enzyme 2 (ACE2), which is a protein in the blood that Sars-CoV2, the virus that causes Covid-19, uses to enter human cells.
ACE2 is found not only in lungs, but also the heart, kidneys and tissues lining blood vessels, and there are particularly high levels in the testes. Its regulation in the testes may partially explain higher ACE2 concentrations in men, and why men are more vulnerable to Covid-19.
In China, where Covid-19 originated, men accounted for close to two-thirds (64%) of deaths as compared to women, who accounted for 36% of all deaths.
The role that ACE2 plays in COVID-19 is important in our understanding of the disease and could be used as a target for therapy. Drugs could be designed to block the receptor function of ACE2, but also there is promise in using the molecule itself in preventing entry of the virus into cells.
This would protect organs such as the lung, heart, kidney and intestine from extensive damage, and hopefully reduce mortality.