Attached paper might answer some of your questions.

Great !! Thank you very much for this article. I see that the last sentence about ACE inhibitors is :" It is certainly worthwhile to test these drugs for their ability to block the RBD/ACE2 interaction. " It is exactly what I think !!! But why

nobody has tested them ?

There are attempts to design a protein that mimics the structure of the ACE2 to bind to the virus. I think and prefer siRNA, especially since the complete genome sequence of the virus has been determined.

Thank you Merwan, you are right ! But I am searching a molecule already available on the market, well-tolerated, frequently used in clinical as AEC1 inhbitors,

...But also, into this attached article, a ACE -2 inhibitor, the N-(2-aminoethyl)-1 aziridine-ethanamine may be effective in blocking the SARS coronavirus spike protein-mediated cell fusion ! What a nice result !

But this artcile has been published in 2004, And since... Nothing....

Has someone already tried this molecule ?...Maybe we could try in inhalation ?

.

..Or maybe we could try ACE 1 inhibitors (inhaled? ) ...I can not imagine that nobody has tried that ...

Lisinopril , captopril , enalapril do not inhibit ACE 2 activity. (Tipnis et al 2000; Donoghue et al, 2000; Soler et al 2008);

And tend to increase ACE2 expression, as angiotensin II inhibitors do.

And Dr Gurtwitz explains: "higher ACE2 expression following chronically medicating SARS-CoV-2 infected patients with AT1R blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS."

=> So, instead of blocking -ECA2, should we aim at increasing ECA2 expression ?

Soler et al indicate that estradiol increased ACE2 protein and gene expression :

=> May this mechanism may contribute to a better protection against Covid-19 infection in women?

The role of ACE-2 inhibitors with COVID-19 is unclear . However read the following:

https://www1.racgp.org.au/newsgp/clinical/ace-inhibitors-arbs-and-covid-19-what-gps-need-to

Thank you so much Anju! ...

So...., until there is evidence that the patient's condition worsens under sartan / IEC or NSAIDs, the balance between theoretical risk of worsening the infection Versus benefit on the overall symptomatology of pneumonia , remains, to my point of view, difficult to assess…

For those ( french speaking, sorry) interested :

Mais …je ne sais pas s’il faut vraiment aller dans le sens d’un remplacement du sartan ou IECA par un inhibiteur calcique : En effet :

=> Arguments en faveur de laisser le sartan ou l’IECA ( démontré avec le losartan le plus souvent) :

- Il up-regule l’expression de l’ ACE2, qui est démontrée comme protectrice sur divers aspects de la symptomatologie du SARS.(soler 2008, Kuba 2005 et Imai 2005).

- Il aurait un effet protecteur à lui seul, ACE2-indépendant (Imai 2005). Et les IECA diminuent l’effet de l’ECA(1), qui est délétère : Il est donc attendu qu’ils soient également protecteurs de façon ECA2-indépendante.

- Augmenter les ACE2 n’a pas été démontré in vivo comme aggravant la symptomatologie, et dans d’autres pathologies comme celle induite par le HIV, augmenter la cible du virus ne se serait pas traduit par une aggravation de l’infection (Gurtwitz 2020).

- Hasard étonnant : les estrogènes (Soler 2008) upregulent l’ACE2, et les femmes semblent être relativement protégées du Covid.19 par rapport aux hommes (OFSP).

- Si on arrête les sartans et IECA à cause du fait qu’ils upregulent les ECA2, quid du turn over de l’expression/degradation de cette protéine, et donc du temps qu’il faudra pour que l’ECA2 revienne à la normale (pour les CYP on parle souvent de2 semaines minimum) ?

-Recommandé par Société de Cardiologie Européenne.

=> Arguments pour remplacer le sartan ou un IECA par un inhibiteur calcique:

-- Ils upregulent l’expression de ACE2, porte d’entrée du Covid19 (li 2003) : Ceci peut, théoriquement, aggraver l’infection. ( c’est sur cet argument que les AINS sont aussi déconseillés, mais, il me semble, sans démonstration d’aggravation publiée.)

-- Les patients hypertendus sont plus à risque de contracter la maladie sans raison évidente :un lien avec le traitement par sartan/IECA et l’infection Covid 19 ne peut être exclu.

--Stratégie proposée par des experts : Fang et al, Lancet Respir Med 2020 .

Marie Humbert- Claude

I also recommend the article a study has done in China during the outbreak of COVID-19.

Please read through the following link:

https://www.healio.com/cardiology/vascular-medicine/news/online/%7Bfe7f0842-aecb-417b-9ecf-3fe7e0ddd991%7D/cardiology-societies-recommend-patients-taking-ace-inhibitors-arbs-who-contract-covid-19-should-continue-treatment

Thanks. ! So, until now, I also support this position !

Marie Humbert-Claude I read some reports that ACE2 has other biological functions in our body. If we block ACE2, it might impair the other functions**.

** " ACE2 lowers blood pressure by catalysing the cleavage of angiotensin II (a vasoconstrictor peptide) into angiotensin (a vasodilator). ACE2 also serves as the entry point into cells for some coronaviruses. The human version of the enzyme is often known as hACE2. " (Wikipedia)

Marie Humbert-Claude Have you also seen this Cell (2020) paper. The researchers are using drug to block one of the two important proteins (ACE2 and TMPRSS2), TMPRSS2.

Title: " SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor " [see attachment]

In Brief

The emerging SARS-coronavirus 2 (SARS-CoV-2) threatens public health. Hoffmann and coworkers show that SARS-CoV-2 infection depends on the host cell factors ACE2 and TMPRSS2 and can be blocked by a clinically proven protease inhibitor. These findings might help to establish options for prevention and treatment.

Preprint Investigating COVID-19: Quantifying recurring methodological...

Good ideas

This is an interesting idea, people are discussing it:

Decoy ACE2 receptors could be promising COVID-19 infection-preventing drug

https://www.drugtargetreview.com/news/59290/decoy-ace2-receptors-could-be-promising-covid-19-infection-preventing-drug/

Marie Humbert-Claude were you able to find a commercially available ACE2 inhibitor? Did you find another way to inhibit ACE2 without getting a ko cell line or mouse.

Nicotine seems to reduce the ACE-2 expression !

1°) Differential Regulation of the Renin-Angiotensin System by Nicotine in WKY and SHR Glia. Merari F. R. Ferrari & Mohan K. Raizada & Debora R. Fior-Chadi (2008)

2°) Nicotine Modulates the Renin–Angiotensin System of Cultured Neurons and Glial Cells from Cardiovascular Brain Areas of Wistar Kyoto and Spontaneously Hypertensive Rats. Merari F. R. Ferrari & Mohan K. Raizada & Debora R. Fior-Chadi (2007)

3°) Nicotine and the renin-angiotensin system.

Joshua M. Oakes, Robert M. Fuchs, Jason D. Gardner, Eric Lazartigues, and Xinping Yue (2018)

https://www.humanbrainproject.eu/en/follow-hbp/news/could-nicotine-help-against-covid-19/