Sexy Enzymes

Viruses, nasty as they are, are often smart enough to capitalize on hijacking bits of humans that are, well, pretty important to humans - to the point that in some cases it can even be tricky to draw the line at where we end, and viruses begin. SARS-CoV-2, the virus that causes the novel coronavirus wrecking havoc across the world in 2020, is no different.

If you've been following along on the last two Microbial Mondays posts (here, and here), you have already heard me mention something called "ACE2". One of the ways in which SARS-CoV-2 relies on us humans, as many viruses do, is already at the very first point in viral infection. The coronavirus needs to ring a doorbell to enter our human cells, where it will replicate - SARS-CoV-2 can't get into our cells without it. In the case of SARS-CoV-2, that doorbell that it rings is called ACE2.

One of the nasty things about the virus using ACE2, is that this protein isn't exactly dispensable for us humans. In fact, ACE2 helps control heart functioning, which I'd say is a pretty important role. But how does it do that?

The answer is actually in its name: ACE2 stands for "angiotensin-converting enzyme", which is science-talk for, "little machine made of protein that cuts up hormones to send messages to your blood vessels". ACE2 sits on the surface of many different human cells, such as lung, kidney, and heart cells, and regulates hormonal messages in your bloodstream that inform blood vessels whether to relax or constrict. This has downstream (pun intended) influences on the functioning of your heart. Basically, the job of ACE2 is to say, "Dude... Chill," to your cardiovascular system.

This chill attitude of ACE2 has already made it an interesting target for treating cardiovascular disease. When an enzyme has potential to be used as a therapy for a major killer like cardiovascular disease, that enzyme becomes sexy for scientists, and they hop aboard the research train to find out more. In this case, this has put us in the lucky position that we already know quite a lot about that doorbell that SARS-CoV-2 is hijacking.

And, that's not even the only way in which we are lucky. We also happen to have already thought about targeting ACE2 as an antiviral. Why, you ask? Because we already had a brush with a SARS coronavirus in 2003, and that nasty 2003 virus hijacks ACE2 in the same way. "Glück im unglück", ("luck in un-luck" - I don't think there is a perfect English translation for this) as my German friends would say.

So what is our plan, now? Scientists have been working on making versions of ACE2 that are not attached to any cells that we can give to patients, to confuse the viruses. The coronavirus isn't smart enough to tell the difference between a cell-attached-ACE2 and a floating-around-ACE2, meaning that they'll be ringing doorbells that are not attached to any house, and therefore not getting in anywhere.

Last week on Microbial Mondays was a bit of a 'downer', with a discussion about how although we are doing our best, it may take a while for scientists to come up with a good vaccine against COVID-19. Soluble ACE-2, i.e. that free-floating ACE2 that we can confuse the virus with, is a different story. Researchers at UBC, in Canada, have already shown that soluble ACE2 can prevent infection of human organs, using mini lab-grown blood vessels and kidneys. The hope is that, because it will take a while to have a good vaccine ready, we can use medications like this to stymie the virus in more severe cases, so that we can go back to normal as soon as possible.

So, here's to all the scientists who have been hard at work in the lab working on many different ways to combat this virus. And, also to the scientists who did that initial research on ACE2 - before we ever suspected it could become part of the cure for cardiovascular diseases or SARS coronaviruses. They set the stage for us to fight off this virus using ACE2, long before ACE2 became scientifically sexy.

Til next week - give some thanks to those basic researchers.

~ Alex