ACEI/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking

doi:10.1186/s13054-020-03195-9

. 2020 Jul 31;24(1):475.

doi: 10.1186/s13054-020-03195-9.

ACEI/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking

Chidinma L Onweni¹, Yu Shrike Zhang², Thomas Caulfield^{3

4}, Christopher E Hopkins^{5

6}, De Lisa Fairweather^{7

8}, William D Freeman^{9

10}

Affiliations

¹ Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, USA.
² Division of Engineering in Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
⁴ Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
⁵ Brigham and Women's Hospital, Boston, MA, USA.
⁶ InVivo Biosystems, Eugene, OR, USA.
⁷ Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, USA.
⁸ Department of Immunology, Mayo Clinic, Jacksonville, FL, USA.
⁹ Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, USA. freeman.william1@mayo.edu.
¹⁰ Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA. freeman.william1@mayo.edu.

PMID: 32736573
PMCID: PMC7393248
DOI: 10.1186/s13054-020-03195-9

ACEI/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking

Chidinma L Onweni et al. Crit Care. 2020.

. 2020 Jul 31;24(1):475.

doi: 10.1186/s13054-020-03195-9.

Authors

Chidinma L Onweni¹, Yu Shrike Zhang², Thomas Caulfield^{3

4}, Christopher E Hopkins^{5

6}, De Lisa Fairweather^{7

8}, William D Freeman^{9

10}

Affiliations

¹ Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, USA.
² Division of Engineering in Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
⁴ Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
⁵ Brigham and Women's Hospital, Boston, MA, USA.
⁶ InVivo Biosystems, Eugene, OR, USA.
⁷ Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL, USA.
⁸ Department of Immunology, Mayo Clinic, Jacksonville, FL, USA.
⁹ Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL, USA. freeman.william1@mayo.edu.
¹⁰ Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA. freeman.william1@mayo.edu.

PMID: 32736573
PMCID: PMC7393248
DOI: 10.1186/s13054-020-03195-9

No abstract available

Keywords: ACE2; ACEI/ARB therapy; COVID-19.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Model for engagement of renin-angiotensin-aldosterone system with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus binds angiotensin-converting enzyme (ACE) 2 (ACE2), promoting internalization of the viral receptor. ACE2-dependent production of angiotensin-(1-7) is disrupted, and production of angiotensin II-(1-8) increases. Changes in angiotensin levels alter the target receptor activity in select tissues. Major organs for gene expression are represented with images, and sites for secondary expression are listed in parentheses. Underlining indicates that the data are from only cell-line analysis. AGT indicates angiotensinogen; AT1, angiotensin II type 1 receptor; AT2, angiotensin II type 2 receptor; CoV-2, coronavirus 2; COVID-19, coronavirus disease 2019; MAS, mitochondrial assembly; TMPRSS2, transmembrane serine protease 2. Expression data were sourced from the Human Protein Atlas (https://www.proteinatlas.org); organ icons made by Vitaly Gorbachev, Smashicons, Prettycons, and Freepik from www.flaticon.com

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References

1. Sungnak W, Huang N, Becavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681–687. doi: 10.1038/s41591-020-0868-6. - DOI - PMC - PubMed
1. Singh AK, Gupta R, Misra A. Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers. Diabetes Metab Syndr. 2020;14:283–287. doi: 10.1016/j.dsx.2020.03.016. - DOI - PMC - PubMed
1. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020:10.1002/ddr.21656. 10.1002/ddr.21656. Online ahead of print. - PMC - PubMed
1. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-81. 10.1161/CIRCRESAHA.120.317134. Epub 2020 Apr 17. - PMC - PubMed
1. Hodgson J. The pandemic pipeline. Nat Biotechnol. 2020;38:523–532. doi: 10.1038/d41587-020-00005-z. - DOI - PubMed

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[1] Sungnak W, Huang N, Becavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681–687. doi: 10.1038/s41591-020-0868-6. - DOI - PMC - PubMed

[2] Sungnak W, Huang N, Becavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681–687. doi: 10.1038/s41591-020-0868-6. - DOI - PMC - PubMed

[3] Singh AK, Gupta R, Misra A. Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers. Diabetes Metab Syndr. 2020;14:283–287. doi: 10.1016/j.dsx.2020.03.016. - DOI - PMC - PubMed

[4] Singh AK, Gupta R, Misra A. Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers. Diabetes Metab Syndr. 2020;14:283–287. doi: 10.1016/j.dsx.2020.03.016. - DOI - PMC - PubMed

[5] Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020:10.1002/ddr.21656. 10.1002/ddr.21656. Online ahead of print. - PMC - PubMed

[6] Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020:10.1002/ddr.21656. 10.1002/ddr.21656. Online ahead of print. - PMC - PubMed

[7] Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-81. 10.1161/CIRCRESAHA.120.317134. Epub 2020 Apr 17. - PMC - PubMed

[8] Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-81. 10.1161/CIRCRESAHA.120.317134. Epub 2020 Apr 17. - PMC - PubMed

[9] Hodgson J. The pandemic pipeline. Nat Biotechnol. 2020;38:523–532. doi: 10.1038/d41587-020-00005-z. - DOI - PubMed

[10] Hodgson J. The pandemic pipeline. Nat Biotechnol. 2020;38:523–532. doi: 10.1038/d41587-020-00005-z. - DOI - PubMed

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ACEI/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking

Affiliations

ACEI/ARB therapy in COVID-19: the double-edged sword of ACE2 and SARS-CoV-2 viral docking

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