Royal College of Surgeons in Ireland
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Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity

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journal contribution
posted on 2022-03-15, 17:08 authored by Maryam Eskandari Mehrabadi, Roohullah Hemmati, Amin Tashakor, Ahmad Homaei, Masoumeh Yousefzadeh, Karim Hemati, Saman Hosseinkhani
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of COVID-19, is reported to increase the rate of mortality worldwide. COVID-19 is associated with acute respiratory symptoms as well as blood coagulation in the vessels (thrombosis), heart attack and stroke. Given the requirement of angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 entry into host cells, here we discuss how the downregulation of ACE2 in the COVID-19 patients and virus-induced shift in ACE2 catalytic equilibrium, change the concentrations of substrates such as angiotensin II, apelin-13, dynorphin-13, and products such as angiotensin (1-7), angiotensin (1-9), apelin-12, dynorphin-12 in the human body. Substrates accumulation ultimately induces inflammation, angiogenesis, thrombosis, neuronal and tissue damage while diminished products lead to the loss of the anti-inflammatory, anti-thrombotic and anti-angiogenic responses. In this review, we focus on the viral-induced imbalance between ACE2 substrates and products which exacerbates the severity of COVID-19. Considering the roadmap, we propose multiple therapeutic strategies aiming to rebalance the products of ACE2 and to ameliorate the symptoms of the disease.



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Published Citation

Mehrabadi ME, et al. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed Pharmacother. 2021;137:111363.

Publication Date

5 February 2021

PubMed ID



  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences


Elsevier B.V.


  • Published Version (Version of Record)