6 ms·

I wonder if this would theoretically work just as well on the new Mink mutated version as well.

dharma1 6y ago
AFAIK the way soluble ACE2 therapy works is you flood the body with "dummy" targets for SARS-CoV-2 to bind to instead of real cells, to slow down the virus infecting more and more cells. As long as the spike of the new mink strains still binds to ACE2, it should provide some benefit.
- sokoloff 6y ago
  (My biology background is incredibly weak.) How would this work? How much medicine would you need to take to get enough dummy targets in your system to make a difference?
  - dharma1 6y ago
    I don't know the doses, but the procedure and effects are described in the linked article. Previous studies have shown human soluble ACE2 can reduce viral load by a factor of 1,000-5,000. "Nine days after the onset of symptoms, the patient received hrsACE2 twice daily for 5 min by intravenous infusion. Administration of hrsACE2 was continued as scheduled for 7-days and was well tolerated with no clear drug-related side effects. A marked reduction in serum angiotensin II levels with concomitant increases in angiotensin 1–7, angiotensin 1–9, and their metabolite angiotensin 1–5 was observed after the first dose of hrsACE2. These changes were sustained through the observation period. Significant ACE2 activity was observed 7-days after administration of the last dose of hrsACE2. In addition, marked decreases in the concentrations of critical cytokines implicated in COVID-19 pathology to include interleukin IL-6, chemokine IL-8, as well as the soluble receptor for advanced glycation end product, the inflammation marker ferritin, tumor necrosis factor α, surfactant protein-D, C-reactive protein, and angiopoietin 2 were observed. The copy number of SAR-CoV-2 decreased dramatically from 32,000 copies per mL 2 days before administration of hrsACE2 to 2,500 and 270 copies per mL after the first and second day of hrsACE2 treatment, respectively, with rapid clearance from the patient’s plasma during daily testing until the end of the observation period. Furthermore, hrsACE2 injection did not reduce the generation of anti-SARS-CoV-2 IgA and IgG antibodies"
philipn 6y ago
Yes, this is one reason why an approach using a form of soluble ACE2 is so promising; mutations that would normally cause e.g. monoclonal antibodies to stop working (as detailed with the mink mutation) would in theory not stop the 'decoy receptor' approach. Despite the fact soluble ACE2 is not looking like it'll be developed in time to impact the pandemic, there is a silver lining: If you look at the original paper (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30418-5/fulltext https://www.thelancet.com/journals/lanres/article/PIIS2213-2...), you'll note they include details on angiotensin peptide levels in the patient. Interestingly, in this n=1 case report, it looks like the soluble ACE2 is unlikely to have worked as an antiviral; the patient already had a high level of antibodies, as you can see in the Lancet paper above. So /if/ the patient's improvements can be ascribed to the soluble ACE2 treatment, it's likely the improvement was because of the effect the soluble ACE2 had on the person's renin-angiotensin system. And if this holds, then it's likely many of these same improvements would be possible using a common class of widely-available blood pressure medications called ARBs. This approach would not neutralize the virus, but instead stop the body from damaging itself. That's the theory, at least. There are ~20 trials of ARBs for COVID-19 in progress now, though almost all are underdosed.

AFAIK the way soluble ACE2 therapy works is you flood the body with "dummy" targets for SARS-CoV-2 to bind to instead of real cells, to slow down the virus infecting more and more cells. As long as the spike of the new mink strains still binds to ACE2, it should provide some benefit.

sokoloff 6y ago
(My biology background is incredibly weak.) How would this work? How much medicine would you need to take to get enough dummy targets in your system to make a difference?
- dharma1 6y ago
  I don't know the doses, but the procedure and effects are described in the linked article. Previous studies have shown human soluble ACE2 can reduce viral load by a factor of 1,000-5,000. "Nine days after the onset of symptoms, the patient received hrsACE2 twice daily for 5 min by intravenous infusion. Administration of hrsACE2 was continued as scheduled for 7-days and was well tolerated with no clear drug-related side effects. A marked reduction in serum angiotensin II levels with concomitant increases in angiotensin 1–7, angiotensin 1–9, and their metabolite angiotensin 1–5 was observed after the first dose of hrsACE2. These changes were sustained through the observation period. Significant ACE2 activity was observed 7-days after administration of the last dose of hrsACE2. In addition, marked decreases in the concentrations of critical cytokines implicated in COVID-19 pathology to include interleukin IL-6, chemokine IL-8, as well as the soluble receptor for advanced glycation end product, the inflammation marker ferritin, tumor necrosis factor α, surfactant protein-D, C-reactive protein, and angiopoietin 2 were observed. The copy number of SAR-CoV-2 decreased dramatically from 32,000 copies per mL 2 days before administration of hrsACE2 to 2,500 and 270 copies per mL after the first and second day of hrsACE2 treatment, respectively, with rapid clearance from the patient’s plasma during daily testing until the end of the observation period. Furthermore, hrsACE2 injection did not reduce the generation of anti-SARS-CoV-2 IgA and IgG antibodies"

philipn 6y ago

Yes, this is one reason why an approach using a form of soluble ACE2 is so promising; mutations that would normally cause e.g. monoclonal antibodies to stop working (as detailed with the mink mutation) would in theory not stop the 'decoy receptor' approach. Despite the fact soluble ACE2 is not looking like it'll be developed in time to impact the pandemic, there is a silver lining: If you look at the original paper (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30418-5/fulltext https://www.thelancet.com/journals/lanres/article/PIIS2213-2...), you'll note they include details on angiotensin peptide levels in the patient. Interestingly, in this n=1 case report, it looks like the soluble ACE2 is unlikely to have worked as an antiviral; the patient already had a high level of antibodies, as you can see in the Lancet paper above. So /if/ the patient's improvements can be ascribed to the soluble ACE2 treatment, it's likely the improvement was because of the effect the soluble ACE2 had on the person's renin-angiotensin system. And if this holds, then it's likely many of these same improvements would be possible using a common class of widely-available blood pressure medications called ARBs. This approach would not neutralize the virus, but instead stop the body from damaging itself. That's the theory, at least. There are ~20 trials of ARBs for COVID-19 in progress now, though almost all are underdosed.