A very long time ago, my bicycle was named ACE by me for obvious reasons- to ace at various activities. ACE is back in my life with ACE2, which is actually nothing like the ACE I was familiar with.
We know that ACE2 is a receptor for the SARS-CoV-2 virus. What is this ACE2?
It is an enzyme whose full name is Angiotensin-converting enzyme 2 (ACE2). This is found on the surface of cells in the lungs, arteries, heart, kidney and intestines. So a lot of very important organs can be entry points for the virus. Can this be an important part to look at during drug development?
This enzyme is known to be a key player in RAAS-lila, I mean RAAS (Renin Angiotensin Aldosterone System) . This is a key hormone system that regulates our blood pressure. The only thing we need to remember is that ACE2 negatively regulates RAAS and shows a positive function in the cardiovascular system.
Can ACE2 receptors be an interesting area to look at COVID drugs?
As discussed earlier, when the Sars-CoV-2 tries to enter, its S protein has to be split at 2 sites by a protease called furin. The protease TMPRSS2 is used for S protein priming and is thus an important protease inhibitor to look at. This complex sounding protease which sounds like temp RSS 2 (no politics, please!) is necessary for the virus to infect our host cells and spread.
There have been some therapies like camostat mesylate which is an approved drug already and is a TMPRSS2 protease inhibitor that can block SARS-CoV-2 from infecting and spreading. Similarly ACE2 antibodies can be used to block the virus from binding to this receptor in the first place.
RAS blockade has been proposed as a potential treatment for COVID-19.
What about anti-hypertensive drugs ?
Given how closely ACE2 interacts with blood pressure, a lot of research and clinical studies have been done on angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) inhibitors as opposed to other drugs for blood pressure.
Based on the study done by Mayo clinic and others, it was recommended to continue these drugs.
The possibility of using recombinant ACE2, Ang 1-7 peptides, ang II receptor inhibitors, and, potentially, aldosterone synthase inhibitors, for preventing or mitigating acute lung injury caused by viruses is unknown. Some studies have been reported using recombinant ACE2 to counter the virus. However much more validation needs to be done.