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CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2021; 57(04): 186-196
DOI: 10.1055/s-0041-1729781
Review Article

Role of ACE 2 and Vitamin D: The Two Players in Global Fight against COVID-19 Pandemic

Tapan Behl
1   Department of Pharmacology, Chitkara University, Punjab, India
,
Sadia Shah
2   Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
,
Ishnoor Kaur
1   Department of Pharmacology, Chitkara University, Punjab, India
,
Sushma Yadav
3   Department of Obstetrics and Gynaecology, Shaheed Hasan Khan Mewati Government Medical College, Haryana, India
,
Raj Kanwar
4   Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
,
Sandeep Seth
5   Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
,
Naveet Wig
6   Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
,
K. K. Sharma
7   National Academy of Medical Sciences (India), New Delhi, India
,
Harlokesh Narayan Yadav
2   Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
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Abstract

The global pandemic of coronavirus disease 2019 (COVID-19) has spread across the borders, gaining attention from both health care professional and researchers to understand the mode of entry and actions induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its causative agent in the human body. The role of angiotensin-converting enzyme–2 (ACE2) in facilitating the entry of the virus in the host cell by binding to it is similar to SARS-CoV-1, the causative agent for severe acute respiratory syndrome (SARS) which emerged in 2003. Besides the role of ACE2 as a molecular target for the virus, the review displays the potential benefits of ACE2 enzyme and various agents that modify its activity in curbing the effects of the deadly virus, thus unfolding a dual character of ACE2 in the current pandemic. As evident by the differences in the susceptibility toward viral infection in children and geriatric population, it must be noted that the older population has limited ACE2 levels and greater infection risk, whereas the situation is reversed in the case of the pediatric population, demonstrating the defensive character of ACE2 in the latter, despite acting as receptor target for SARS-CoV-2. Also, the upregulation of ACE2 levels by estrogen has indicated greater resistance to infection in females than in the male human population. ACE2 is a carboxypeptidase, which degrades angiotensin II and counteracts its actions to protect against cardiovascular risks associated with the virus. Another contribution of this enzyme is supported by the role of circulating soluble ACE2, which acts as a receptor to bind the virus but does not mediate its actions, therefore blocking its interaction to membrane-bound ACE2 receptors. The review also shares the enhanced risks of developing COVID-19 infection by using ACE inhibitors and ARBs. However, both these agents have been reported to upregulate ACE2 levels; yet, adequate evidence regarding their role is quite inconsistent in human studies. Furthermore, the role of vitamin D has been highlighted in regulating the immune system of the body through renin-angiotensin-aldosterone system (RAAS) inhibition, by downregulating host cell receptor expression to prevent virus attachment. Besides, vitamin D also acts through several other mechanisms like upregulating antimicrobial peptides, fighting against the proinflammatory milieu created by the invading virus, and interfering with the viral replication cycle as well as calcitriol-mediated blockage of CREB protein. Hypovitaminosis D is attributed to elevated risks of acute respiratory distress syndrome (ARDS), lung damage, and cardiovascular disorders, further increasing the severity of COVID-19 infection.

Keywords

ACE2 - molecular target - angiotensin II - ACE inhibitors - ARBs - vitamin D - calcitriol


Publication History

Article published online:
09 June 2021

© 2021. National Academy of Medical Sciences (India). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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