Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Nov 3;5(1):258.
doi: 10.1038/s41392-020-00374-6.

Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID-19

Affiliations
Comment

Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID-19

Tarek Mohamed Abd El-Aziz et al. Signal Transduct Target Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic diagram of the renin-angiotensin system and the proposed therapeutic treatment for COVID-19 targeting SARS-CoV-2 viral entry mechanism. (Left) The receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 binds to ACE2, allowing host cell entry and infection. TMPRSS2 indicates transmembrane protease serine 2. (Middle) The physiological role of ACE2 in renin-angiotensin system and its protective effect on organs. The protease renin, an enzyme produced by the juxtaglomerular cells of the kidney, cleaves angiotensinogen (a precursor of angiotensin produced by the liver) to generate angiotensin I. ACE plays an important role in converting angiotensin I into angiotensin II. Angiotensin II may exert some biological functions through angiotensin II receptor type 1 and 2 receptors (AT1R and AT2R), leading to potent vasoconstriction in several organs. Activation of AT1R increases the transmembrane proteinase (ADAM17) activity. Furthermore, tumor necrosis factor-α (TNF-α) activation of its tumor necrosis factor receptor (TNFR) represents another pathway increasing ADAM17 activity. TNF-α along with cytokines released due to SARS-CoV-2 infection can lead to a cytokine storm. ADAM17 cleaves the extracellular juxta-membrane region of ACE2, whether such ACE2 cleavage contributes to SARS pathogenesis is not known yet. ACE2 hydrolyzes Angiotensin II to the vasodilator Angiotensin 1–7, which binds the Mas receptor and plays a protective role in several organs. The balance between ACE/Ang II/AT1R and ACE2/Ang 1–7/MasR is vital for maintaining normal health. (Right) According to recent studies, increasing of hrsACE2 at tissue sites can effectively compete with the endogenous ACE2 and limits SARS-CoV-2 entrance into the host cells and decreases angiotensin II levels., Significantly, hrsACE2 injection did not reduce the generation of anti-SARS-CoV-2 IgA and IgG antibodies

Comment on

  • Human recombinant soluble ACE2 in severe COVID-19.
    Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS, Penninger JM. Zoufaly A, et al. Lancet Respir Med. 2020 Nov;8(11):1154-1158. doi: 10.1016/S2213-2600(20)30418-5. Epub 2020 Sep 24. Lancet Respir Med. 2020. PMID: 33131609 Free PMC article. No abstract available.

References

    1. Zoufaly, A. et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respiratory Med.10.1016/S2213-2600(20)30418-5 (2020). - PMC - PubMed
    1. Walls AC, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181:281–292.e286. doi: 10.1016/j.cell.2020.02.058. - DOI - PMC - PubMed
    1. Kuba K, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 2005;11:875–879. doi: 10.1038/nm1267. - DOI - PMC - PubMed
    1. Monteil V, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020;181:905–913.e907. doi: 10.1016/j.cell.2020.04.004. - DOI - PMC - PubMed
    1. Haschke M, et al. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin. Pharmacokinetics. 2013;52:783–792. doi: 10.1007/s40262-013-0072-7. - DOI - PubMed

Substances