Coronavirus: "ACE2" blocks infection in lab

Scientists have successfully used a drug to 'trick' the coronavirus out of infecting cells in the lab...
21 April 2020

Interview with 

Josef Penninger, University of British Columbia


A line of differently-shaped pills.


There’s a huge effort going in laboratories around the world to find a treatment for COVID-19 and a vaccine. And in Vancouver, a team of scientists may have found a way to stop the coronavirus infecting cells in the lungs. They’ve used a drug called “soluble ACE2” that acts as a decoy to the virus, so instead of attacking human cells, it attacks the drug instead. Chris Smith heard more from researcher Josef Penninger...

Josef - We tried to find out if a molecule we had engineered, which looks basically like the gates the virus needs to infect us... if blocking the gate could actually be used to block the virus. And this is exactly what happened.

Chris - Right, so there is a target on cells that the virus wants to infect, and it looks for that target and uses that as the doorway. You're saying if we make a fake doorway, we can fool the virus into spending all its time trying to go through a doorway that's broken, rather than one that really exists into the cell?

Josef - Correct. This is exactly what we tested in our paper. We infected cells with the virus and basically gave them this wrong doorway, and by giving the wrong doorway we could reduce the virus infection by a factor of 1,000-5,000 times.

Chris - What's the doorway?

Josef - The doorway is a molecule which we call angiotensin converting enzyme number 2. The normal function is actually to maintain our blood pressure, to protect our heart, to protect our kidney, to protect our lungs from inflammation processes, which actually are damaging our tissues. When the virus binds to this molecule ACE2, it actually takes it away from the surface of the cell. And this is the reason why we believe SARS and now COVID-19 became such lethal diseases: because it's actually hit the molecule which is protecting multiple tissues in our body. So we basically give a molecule and engineer the molecule, which looks like ACE2, but basically free floats around in the body, so it does not allow the virus to get into the cells.

Chris - And how far have you got with testing this? What have you done so far?

Josef - What we have shown so far is that in cells grown in a dish, this can indeed block the infection by a factor of 1,000-5,000 times.

Chris - Obviously you've intervened at what would be an early stage of the infection, but many people don't develop severe disease until they've had it for quite a while. It's almost like it falls into two phases; there's the initial fairly mild phase, and then the other effects and the deterioration kick in later. Would it be by then too late for this?

Josef - You're absolutely right. This is an important consideration. We’ve got now the commission to do a phase two clinical study in COVID-19 patients, and the patients we will treat are actually patients who have severe disease, so who are already at the later stage of the disease. The reason why we do this is because in these patients, the virus is actually spreading from the lung into other tissues, into the kidney, into the liver, into the heart, and of course we hope that our drug candidate can catch away the virus so it does not reach these other tissues.

Chris - The question is though, why is it that four fifths of people will bat this away with very, very, very trivial symptoms, and only about a fifth of people will develop more severe disease? Everyone's got this angiotensin system running in their body. So why is it that some people end up needing help from molecules like the one you've invented, and others don't?

Josef - Yeah, honestly I have no idea. I think this is one of the critical questions of why is it that somebody has a hyperactive immune system, which of course drives the disease, and I think this will be a very important question to answer. Why is it that older people are mostly affected with severe disease? We do know that for instance, younger people have less ACE2, older people have much more ACE2. We do know that smoking for instance induces ACE2 in the lung. Diabetes induces ACE2. So basically in these conditions there would be more receptors, more doorways available for the virus to infect us. This could partially explain this phenomenon why some people get it worse, but I think there must be other answers like an ageing immune system for instance.


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