Re: Response to the emerging novel coronavirus outbreak
Dear Editor,
The possible therapeutic role of Angiotensin II receptor blockers (ARIIB) in the Corona epidemic.
There is evidence to support that Covid-19 virus is using the ACE2 receptor for cell entry(1,2). We are extremely lucky if this is the case as Renin Angiotensin System (RAS) is one of the best studied and manipulated pathways in medicine.
If we look at the available research on ACE2 it is evident that ACE2 plays a crucial role in Angiotensinogen II metabolism. ACE2 converts Angiotensin II to Angiotensin 1-7 a molecule with vasodilator properties. ACE2 plays a role in converting Ang II (Vasoconstrictor) to Ang 1-7 production (Ang 1-7 is a potent vasodilators). Angiotensinogen II is a potent vasoconstrictor and can cause oxidative stress to lung tissue.
Therefore, ACEII plays a significant role in preventing deleterious effects of Angiotensin II in lung tissue(3). When the virus interacts with the ACEII molecule it gets internalized exposing lungs to unopposed action of ACEII. It has been postulated that one of the mechanisms of corona virus related lung injury is that lack of ACEII on surface of pneumocytes.
Furthermore, ACE2 expression is abundant in the kidney and is thought to provide protection against injury(4).
There are articles published in Chinese language suggesting that ACE inhibitors and ARIIB can be used as a therapeutic agent (5). However, looking at the above-mentioned lung/renal injury mechanism ACE Inhibitors are unlikely to be helpful.
In light of this evidence there is a need to:
1. see the prevalence of ARDS among corona virus infected patients who are already on ARII blockers.
2. assess ARIIB (a well tested drug for other indications) as a therapeutic agent to prevent ARDS and AKI in corona virus infected high-risk patients. (Not ACE Inhibitors)
References.
1. Bosch BJ, Smits SL, Haagmans BL. Membrane ectopeptidases targeted by human coronaviruses. Curr Opin Virol. 2014 Jun;6:55-60. doi: 10.1016/j.coviro.2014.03.011. Epub 2014 Apr 22. PMID: 24762977; PMCID: PMC4072739
2. Wan Y, Shang J, Graham R, Ralph S. Baric, Fang Li. Receptor recognition by novel coronavirus from Wuhan: 3 An analysis based on decade-long structural studies of SARS. Journal of virology. J. Virol. doi:10.1128/JVI.00127-20
3. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436:112–116. [PubMed] [Google Scholar
4. Williams, Vanessa R., Scholey, James W.Angiotensin-converting enzyme 2 and renal disease. Current Opinion in Nephrology and Hypertension: January 2018: Volume 27-Issue 1 p 35-41.doi: 10.1097/MNH.0000000000000378.
5. Sun M, Yang J, Sun Y, Su GH.Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia 2020 Feb 16;43(0):E014. doi: 10.3760/cma.j.issn.1001-0939.2020.0014. [Epub ahead of print]
Competing interests:
No competing interests
17 March 2020
M D Vajira Malin Gunawardena
Cardiologist
Consultant Cardiologist Ministry of Health Sri Lanka
Rapid Response:
Re: Response to the emerging novel coronavirus outbreak
Dear Editor,
The possible therapeutic role of Angiotensin II receptor blockers (ARIIB) in the Corona epidemic.
There is evidence to support that Covid-19 virus is using the ACE2 receptor for cell entry(1,2). We are extremely lucky if this is the case as Renin Angiotensin System (RAS) is one of the best studied and manipulated pathways in medicine.
If we look at the available research on ACE2 it is evident that ACE2 plays a crucial role in Angiotensinogen II metabolism. ACE2 converts Angiotensin II to Angiotensin 1-7 a molecule with vasodilator properties. ACE2 plays a role in converting Ang II (Vasoconstrictor) to Ang 1-7 production (Ang 1-7 is a potent vasodilators). Angiotensinogen II is a potent vasoconstrictor and can cause oxidative stress to lung tissue.
Therefore, ACEII plays a significant role in preventing deleterious effects of Angiotensin II in lung tissue(3). When the virus interacts with the ACEII molecule it gets internalized exposing lungs to unopposed action of ACEII. It has been postulated that one of the mechanisms of corona virus related lung injury is that lack of ACEII on surface of pneumocytes.
Furthermore, ACE2 expression is abundant in the kidney and is thought to provide protection against injury(4).
There are articles published in Chinese language suggesting that ACE inhibitors and ARIIB can be used as a therapeutic agent (5). However, looking at the above-mentioned lung/renal injury mechanism ACE Inhibitors are unlikely to be helpful.
In light of this evidence there is a need to:
1. see the prevalence of ARDS among corona virus infected patients who are already on ARII blockers.
2. assess ARIIB (a well tested drug for other indications) as a therapeutic agent to prevent ARDS and AKI in corona virus infected high-risk patients. (Not ACE Inhibitors)
References.
1. Bosch BJ, Smits SL, Haagmans BL. Membrane ectopeptidases targeted by human coronaviruses. Curr Opin Virol. 2014 Jun;6:55-60. doi: 10.1016/j.coviro.2014.03.011. Epub 2014 Apr 22. PMID: 24762977; PMCID: PMC4072739
2. Wan Y, Shang J, Graham R, Ralph S. Baric, Fang Li. Receptor recognition by novel coronavirus from Wuhan: 3 An analysis based on decade-long structural studies of SARS. Journal of virology. J. Virol. doi:10.1128/JVI.00127-20
3. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436:112–116. [PubMed] [Google Scholar
4. Williams, Vanessa R., Scholey, James W.Angiotensin-converting enzyme 2 and renal disease. Current Opinion in Nephrology and Hypertension: January 2018: Volume 27-Issue 1 p 35-41.doi: 10.1097/MNH.0000000000000378.
5. Sun M, Yang J, Sun Y, Su GH.Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia 2020 Feb 16;43(0):E014. doi: 10.3760/cma.j.issn.1001-0939.2020.0014. [Epub ahead of print]
Competing interests: No competing interests