Can ACE2 be produced and used as drug against covid? I read it is the receptor molecule. If it is in the organism the virus should bind to it and could not attack cells anymore? Is that right?


There's a Cell pre-print by Monteil et al. (DOI: 10.1016/j.cell.2020.04.004) which argues that human recombinant soluble ACE2 protein can competitively bind to SARS-CoV-2 virus and reduce its ability to infect and replicate:

Here, we report that clinical-grade human recombinant soluble ACE2 (hrsACE2), which has already been tested in phase 1 and phase 2 clinical trials (Haschke et al., 2013, Khan et al., 2017), can reduce viral growth in Vero E6 cells by a factor of 1,000-5,000. Moreover, we show that human blood vessel organoids and kidney organoids can be readily infected, which can be significantly inhibited by hrsACE2 at the early stage of infection.

Though it is not perfect, in that other factors and receptors may be implicated in infectivity:

Our data now show that this clinical-grade human ACE2 molecule - but not mouse soluble ACE2 - can significantly inhibit SARS-CoV-2 infections and reduce viral load by a factor of 1,000-5,000. However, as observed in antibody neutralizing experiments of many viruses, the inhibition is not complete, though clearly dose-dependent. This may be due to the fact that there might be other co-receptors/auxiliary proteins or even other mechanisms by which viruses can enter cells, as had been initially proposed for SARS (Jeffers et al., 2004; Qi et al., 2020).

One person is right to comment that these are in vitro studies. In other words, they treat cell cultures on the functional equivalent of a Petri dish: Vero cell lines or simulations of human tissues (organoids), and they see what happens.

The in vitro studies are useful and important but it is a big step from those to 1) treating people in vivo — designing a drug that can actually and safely target the virus where it infects respiratory and renal tissues — and, 2) making and distributing that drug in quantity, cheaply, safely, etc.

But the larger point of these studies is to show that scientists are definitely thinking about the mechanisms by which the virus infects cells, and to see if there are ways to interfere with and limit the virus, by doing so.

Like your thought to use ACE2, some researchers have looked at other viruses, like poliovirus and HIV, to see if there are similar soluble ligands that they can bond to antibodies and deliver safely to humans, as a general therapeutic idea.

They found that HIV-1, which uses binding to the CD4 receptor as a means to infect T cells, could develop mutational resistance to soluble CD4 and use other mechanisms to cause infection. But by adding a second receptor CCR5 to the immunoglobulin, other researchers were able to limit the ability of HIV-1 virus to evolve resistance to both receptors, which provides some possibility of this approach as a vaccine, down the road.

These issues all complicate use of receptors as a way to "fake out" the virus. But it is an avenue being explored, especially for this virus during a time of emergency.

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    $\begingroup$ It should be noted that the study referenced is in vitro and no efficacy has been demonstrated in actual infected individuals, though there are earlier trials (I assume these are the citations in the quote) showing clinical efficacy in ARDS - I believe that relates to the enzymatic activity of ACE2, though, not anything to do with binding to viral particles, and I don't know of any proof-of-concept that would suggest the receptors make it into the lungs where the virus is. $\endgroup$ – Bryan Krause May 11 at 23:41
  • $\begingroup$ Good points, definitely. Read the preprint in depth. $\endgroup$ – Alex Reynolds May 12 at 3:42
  • $\begingroup$ @AlexReynolds thank you. In that regard I have a question. Has someone tried to use human cells with artificially damaged cell interior that will accept the virus by its ACE2 and other receptors (but not reproduced it and finally destroy it)? $\endgroup$ – Mercury May 12 at 11:12
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    $\begingroup$ I don't know if such a therapy exists. Maybe others would know. Usually these are immunoglobulins, immune system proteins with unique bits attached that a virus would bind to, instead of the receptors on a lung or other cell that it would normally try to infect. $\endgroup$ – Alex Reynolds May 12 at 17:48
  • $\begingroup$ What about any side-effect of "taking away", i.e. scavenging, the natural ligand of ACE2 (which is physiologically expressed on membranes of epithelia and neurons too(?), thus especially leading to a lack of counterbalancing of high blood pressurem as ACE2-axis is considering beneficially downregulating the AngioensinII-AT2-axis? $\endgroup$ – Peter Bernhard Nov 12 at 11:21

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