COVID-19 and ACE2 receptor in different tissues: From pathophysiologic function to therapeutic responses

Document Type : Review Article

Authors

1 Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

2 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

3 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

10.32592/ARI.2025.80.3.691

Abstract

SARS-CoV-2, the virus responsible for COVID-19, is characterized by its high transmission rate, leading to a global pandemic. Millions of people have lost their lives due to the infection caused by this virus. The ability of the virus to spread rapidly and infect large numbers of people has highlighted the need to understand its infection mechanisms. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for SARS-CoV-2 cell entry. SARS-CoV-2 shows high affinity to this receptor and shows high infectivity, which leads to an explosive increase of this virus in patients infected with COVID-19. ACE2 is the carboxypeptidase homolog of ACE, which produces angiotensin II, the main active peptide of the renin-angiotensin system. From a pathophysiological perspective, this system regulates vital processes in different organs. In addition, ACE2 enzyme activity could play a protective role against acute respiratory distress syndrome (ARDS) caused by viral pneumonia. Upon infection, SARS-CoV-2 down-regulates the expression of ACE2, which is possibly related to the ARDS pathogenesis. Since this receptor is present in various other tissues such as the heart, kidney, gastrointestinal tract, reproductive system, and sensory organs, it may cause pathological symptoms in these organs. Thus, ACE2 is not only a receptor for SARS-CoV-2 but may play a crucial role in various aspects of the pathogenesis of COVID-19 and possible post-COVID-19 syndromes. Administering ACE2 may competitively bind to SARS-CoV, thereby preventing the viral spike protein from attaching to the transmembrane ACE2 and consequently reducing viral cell entry and COVID-19 symptoms. Here, we first review the role of ACE2 in the pathophysiology of SARS-CoV-2 across different tissues and propose treatment strategies for COVID-19 that involve ACE2.

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References

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Archives of Razi Institute
Volume 80, Issue 3
May and June 2025
Pages 691-704

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