From the articles I've read on COVID-19 and ACE2 (ACE2 being the binding target for the virus), it appears that both inhaled ACE2 and systemic ACE2, in a recombinant form, may be the solution to preventing and treating this virus. Inhaled ACE2 would serve as a decoy to the virus, preventing binding to our alveoli cells. Systemic ACE2 would reverse some of the effects of the virus inhibiting our lung ACE2, such as pulmonary hypertension and possibly edema. ACE2 is basically opposing ACE in many respects. What are your thoughts?
I used Google Translate to understand your message, and I completely agree. We don't want to rush a therapy and then cause more harm than good.
https://portlandpress.com/clinsci/article/134/5/543/222345/Soluble-angiotensinconverting-enzyme-2-a-potential
http://www.nephjc.com/news/covidace2
Search in the article for: "Delivering excessive soluble form of ACE2"
For some reason this clinical pilot study on ACE2 administration was withdrawn.
https://clinicaltrials.gov/ct2/show/NCT04287686
I agree. I believe a Vienna based company is looking at clinical trials.
@Cgeorge I found this on their website. It looks like they were using it for pulmonary hypertension, but transferred it to GSK. I hope GSK is testing it for COVID-19.
"Our non-IO product APN01, a recombinant enzyme of the Renin Angiotensin System, was out-licensed to GlaxoSmithKline which further validates APEIRON’s robust pipeline."
Inhaled or oral Melatonin would be expected to help
Article Oral melatonin attenuates lung inflammation and airway hyper...
Article Melatonin and Respiratory Diseases: A Review
Fluoride simultaneously reduces Melatonin and increases ACE-2
Hey Adam L Vanwert, first year medical student here. Very interested in this idea and possible benefits for treating COVID-19 with an ACE2 treatment. The first thing I thought when I saw that the virus binds to ACE2 was why are we not trying to block ACE2? I was surprised to see so little when I tried digging into that question. Most of the research that comes up involves outcomes of patients taking oral ACEi or ARBs. It seems to me that if we can decrease the levels of ACE2 in the lungs, theoretically there would be less protein for the virus to bind to. However since most ACEi and ARB treatments are oral, they don’t have much impact on the lungs and have actually been shown to increase the ACE2 levels in the lungs (hence the papers regarding worse outcomes for patients on these treatments.) I would love to talk more about this theory of ACE2 blockers. Please let me know if you’re interested!
Thank you for the reply Evan. I believe inhibiting ACE2 may interfere with it's role in angiotensin II metabolism. However, providing excess ACE2 in an inhaled powder might block the virus from infecting. Someone might argue that it will attract more virus, but attracting a virus to a decoy without a host cell could prevent replication until the immune system destroys the virus.
I do understand your point about the angiotensin II metabolism issue, I was thinking that blocking angiotensin II may be a small price to pay with the overall outcome of blocking the virus. Similar to ACEi/ARBs affecting blood pressure, the body finds ways to compensate. To your point about the inhaled powder, it seems to me that the theory makes sense, however I'm curious as to how the powder itself would be cleared from the lungs. I don't know of other inhaled treatments where the treatment itself isn't actually binding to anything in the lungs, but needs to stay there. If the virus could bind to it however, it wouldn't be able to replicate and would thus be "neutralized" which would have benefits.
What about inhalation or systemic administration of extracellular vesicles loaded with ACE2 on their surface? Recent study have shown that they have better efficiency in preventing viral entry than soluble ACE2.
Sherif Ibrahim I think you have a great idea. Vesicles might give the ACE2 a more natural conformation, and appear more like the endogenous target. I haven't read the literature on this, but the membrane might be an important part of the recognition by the virus.
Two additional points: (1) excess lipid in the lungs is sometimes an issue, for example lipoid pneumonia from mineral oil aspiration. So we would need to be sure the risk is low for irritation from the vesicles; (2) also loading the vesicle with an antiviral might also be a good idea, especially if we had any that blocked a surface protein of the virus. I propose ACE2 and an antiviral for prevention and/or eradication.
Here is a published paper suggesting the idea as a theoretical concept.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298154/
And here is a bioarxiv published paper showing the effect in-vitro:
Preprint Extracellular vesicles containing ACE2 efficiently prevent i...
sACE2 (native soluble ACE2) and/or hrACE2 (human recombinant ACE2) potentially have detrimental role.
Preprint Potential detrimental role of soluble ACE2 in severe COVID-1...
Here is a published paper suggesting the idea as a theoretical concept
What about inhalation or systemic administration of extracellular vesicles loaded with ACE2 on their surface? Recent study have shown that they have better efficiency in preventing viral entry than soluble ACE2