Renin-angiotensin system at the interface of COVID-19 infection

Rukhsana Gul; Uh-Hyun Kim; Assim A Alfadda

doi:10.1016/j.ejphar.2020.173656

Renin-angiotensin system at the interface of COVID-19 infection

Eur J Pharmacol. 2021 Jan 5:890:173656. doi: 10.1016/j.ejphar.2020.173656. Epub 2020 Oct 18.

Authors

Rukhsana Gul¹, Uh-Hyun Kim², Assim A Alfadda³

Affiliations

¹ Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia. Electronic address: rgul@ksu.edu.sa.
² Department of Biochemistry & National Creative Research Laboratory for Ca(2+) Signaling, Chonbuk National University Medical School, Jeonju, 54907, Republic of Korea.
³ Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia; Department of Medicine, College of Medicine, King Saud University, PO Box 2925, Riyadh, 11461, Saudi Arabia; Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Abstract

Angiotensin-converting enzyme 2 (ACE2) has been recognized as a potential entry receptor for SARS-CoV-2 infection. Binding of SARS-CoV-2 to ACE2 allows engagement with pulmonary epithelial cells and pulmonary infection with the virus. ACE2 is an essential component of renin-angiotensin system (RAS), and involved in promoting protective effects to counter-regulate angiotensin (Ang) II-induced pathogenesis. The use of angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEIs) was implicitly negated during the early phase of COVID-19 pandemic, considering the role of these antihypertensive agents in enhancing ACE2 expression thereby promoting the susceptibility to SARS-CoV-2. However, no clinical data has supported this assumption, but indeed evidence demonstrates that ACEIs and ARBs, besides their cardioprotective effects in COVID-19 patients with cardiovascular diseases, might also be beneficial in acute lung injuries by preserving the ACE2 function and switching the balance from deleterious ACE/Ang II/AT₁ receptor axis towards a protective ACE2/Ang (1-7)/Mas receptor axis.

Keywords: ACE2; ACEIs; ARBs and COVID-19; RAS; SARS-CoV-2.

Publication types

Review

MeSH terms

Angiotensin Receptor Antagonists / therapeutic use*
Angiotensin-Converting Enzyme 2 / metabolism
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Animals
COVID-19 / metabolism
COVID-19 Drug Treatment*
Humans
Proto-Oncogene Mas
Proto-Oncogene Proteins / metabolism
Receptors, G-Protein-Coupled / metabolism
Renin-Angiotensin System*
SARS-CoV-2* / physiology
Severe Acute Respiratory Syndrome
Severe acute respiratory syndrome-related coronavirus

Substances

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Proto-Oncogene Mas
Proto-Oncogene Proteins
Receptors, G-Protein-Coupled
Angiotensin-Converting Enzyme 2