Contemporary studies revealed that novel coronavirus (SARS-CoV) use ACE2 receptor to facilitate viral entry into target cells.
Increase circulating ACE2 can slow viral entry into cells and hence viral spread.
What is the kind of drugs that can Increase the circulating ACE2 ?
Yasser Ali Kamal,
Angiotensin receptor blockers were proposed as tentative SARS‐CoV‐2 therapeutics:
Article Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics
Dear Yassser,
Your hypothesis unfortunately is wrong. Mechanism which you describe will not works because even if ACE2 will grooving then still complex |virus+ACE2| will ongoing endocythosis to the cells. So if you want stop viral replication you should block virus affinity and binding to the ACE2 or block endocythosis of |virus+ACE2| complex etc. See an example:
Article Clathrin-Dependent Entry of Severe Acute Respiratory Syndrom...
Best regards,
Tomasz
Dear Tomasz Grabowski,
It is not my hypothesis. Recently, I read an article entitled: "Angiotensin‑converting enzyme 2 (ACE2) as a SARS‑CoV‑2 receptor: molecular mechanisms and potential therapeutic target".
One of these therapeutic targets is soluble form of ACE2 which should slow viral entry into cells through competitively binding with SARS-CoV-2. For more information:
Article Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 recep...
Dear Yasser,
Ok now its clear thank you for sharing the paper.... as some authors state "...Recent clinical investigations have highlighted that elevated levels of soluble ACE2 in patient plasma correlated with increased myocardial dysfunction and vascular compliactions in type 1 diabetes. ..."
Article Soluble Angiotensin-Converting Enzyme 2 in Human Heart Failu...
Article Circulating ACE2 activity is increased in patients with type...
Consequently if soluble ACE2 administration could prevent or help reduce virus replication then sub-populations with diabetes or myocardial dysfunctions should be potentially less exposed for viral COVID infection. Current data not confirm such hypothesis. Unfortunately Authors of the paper you are sharing did not discuss and did not examine this issue, they stopped only on hypotheses. Next question which they not solve is what happens with |soluble ACE2+Virus| complex? Finally such complex probably will undergo internalization or endocytosis and ....then probably virus will be released and can replicate even that. There are many gaps ... but its our role discuss such gaps ....
Thank you again for sharing this paper
Best regards
Tomasz
When developing therapies for Covid-19 please consider the effect of these medications on the QTc interval.
Article Acquired Long QT Syndrome: A Review of the Literature
This review discusses the points I outline below.
A note of caution.
Several medications that have been recommended for the treatment of Covid-19 are associated with prolongation of the QTc interval and therefore torsade de pointes and sudden cardiac death.
The evidence of the potential benefit of chloroquine and hydroxychloroquine in the treatment of Covid-19 is increasing.
Other medications which may be used in this cohort include the macrolide antibiotics (e.g. azithromycin). These can also prolong the QTc interval. Administering several medications that may prolong the QT interval is associated with a high risk of complications.
In medicine risks and benefits must be balanced. Safety netting is important whenever there is a great potential benefit but also a very significant risk. In that context QTc intervals, renal and liver function must be monitored closely in patients treated with chloroquine and or macrolides. They should probably not be started if the baseline QTc is more than 450 ms. It should probably be stopped if the QTc increases 25% above baseline. It should definitely be stopped if QTc is above 500 ms. This is an evolving situation and recommendations may change as the potential risks and benefits become clearer.
Beta-blockade is used in the treatment of congenital and acquired long QT syndrome, so may be beneficial in this setting.
Dear Rajkumar Rajendram
That is rigt
Both hydroxychlorquine and azithromycin ( which used for secondary bacterial invesion) prolong QT interval. Their combination !!!!!!!!!!!!!!!!! could cause arrythmia
Further research is needed on the the mechanisms of the involvement of ACE2 on COVID-19 infection.
Especially when considering the possible association of the angiotensin enzyme inhibitors or angiotensin receptor blockers with the risk of the infection.
Severe acute respiratory syndrome coronavirus 2 infection, angiotensinconverting enzyme 2 and treatment with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers Riccardo Sarzani1,2, Federico Giulietti1,2, Chiara Di Pentima1,2, Piero Giordano1 and Francesco Spannella
Can we manage prophylactic therapy in COVID-19 patients to prevent severe illness complications?
Many patients with COVID-19 have thromboembolic complications that worsen their prognosis. Herein, the authors propose a modified version of the CHA 2 DS 2-VASc score, including 1 point for COVID-19, so that prophylaxis to protect against thromboembolic events would be indicated before the condition becomes severe. The advantages of this modification would be prevention of the patient' s condition worsening due to thromboembolic problems and reduction of the likelihood of a need for intensive care and mechanical ventilation, reducing mortality.
https://www.scielo.br/pdf/jvb/v19/en_1677-5449-jvb-19-e20200057.pdf
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