Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity

Affiliations

¹ Division of Nephrology/Hypertension, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. Electronic address: d-batlle@northwestern.edu.
² Karolinska Institute and Karolinska University Hospital, Department of Laboratory Medicine, Unit of Clinical Microbiology, 17177 Stockholm, Sweden.
³ Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
⁴ Division of Nephrology/Hypertension, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
⁷ Karolinska Institute and Karolinska University Hospital, Department of Laboratory Medicine, Unit of Clinical Microbiology, 17177 Stockholm, Sweden; National Veterinary Institute, 751 89 Uppsala, Sweden.
⁸ Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain.
⁹ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; German Center for Cardiovascular Research (DZHK), Berlin, Germany; Charité Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; University of Lübeck, Institute for Biology, Lübeck, Germany.
¹⁰ Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: josef.penninger@ubc.ca.

PMID: 35623327
PMCID: PMC9134488
DOI: 10.1016/j.cell.2022.05.004

Comment

Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity

Daniel Batlle et al. Cell. 2022.

. 2022 May 26;185(11):1837-1839.

doi: 10.1016/j.cell.2022.05.004.

Authors

Affiliations

¹ Division of Nephrology/Hypertension, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. Electronic address: d-batlle@northwestern.edu.
² Karolinska Institute and Karolinska University Hospital, Department of Laboratory Medicine, Unit of Clinical Microbiology, 17177 Stockholm, Sweden.
³ Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
⁴ Division of Nephrology/Hypertension, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
⁷ Karolinska Institute and Karolinska University Hospital, Department of Laboratory Medicine, Unit of Clinical Microbiology, 17177 Stockholm, Sweden; National Veterinary Institute, 751 89 Uppsala, Sweden.
⁸ Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain.
⁹ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; German Center for Cardiovascular Research (DZHK), Berlin, Germany; Charité Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; University of Lübeck, Institute for Biology, Lübeck, Germany.
¹⁰ Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: josef.penninger@ubc.ca.

PMID: 35623327
PMCID: PMC9134488
DOI: 10.1016/j.cell.2022.05.004

No abstract available

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Conflict of interest statement

Declaration of interests D.B. and J.W. are coinventors of patents entitled “Active Low Molecular Weight Variants of Angiotensin Converting Enzyme 2,” “Active low molecular weight variants of Angiotensin Converting Enzyme 2 (ACE2) for the treatment of diseases and conditions of the eye,” and “Soluble ACE2 Variants and Uses Therefor,” which includes the use of prevention and treatment of COVID-19. D.B. is founder of Angiotensin Therapeutics Inc. D.B. has received consulting fees from AstraZeneca, Relypsa, and Tricida, all unrelated to this work. J.W. reports scientific advisor capacity for Angiotensin Therapeutics Inc. R.E.S. is on the scientific advisory board of Miromatrix Inc and is a consultant and speaker for Alnylam Inc. J.M.P. is shareholder of Apeiron Biologics that is developing soluble ACE2 for COVID-19 therapy.

Comment in

Response to Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity.
Yeung ML, Teng JLL, Yuen KY. Yeung ML, et al. Cell. 2022 May 26;185(11):1840-1841. doi: 10.1016/j.cell.2022.05.005. Cell. 2022. PMID: 35623328 Free PMC article. No abstract available.

Comment on

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.
Yeung ML, Teng JLL, Jia L, Zhang C, Huang C, Cai JP, Zhou R, Chan KH, Zhao H, Zhu L, Siu KL, Fung SY, Yung S, Chan TM, To KK, Chan JF, Cai Z, Lau SKP, Chen Z, Jin DY, Woo PCY, Yuen KY. Yeung ML, et al. Cell. 2021 Apr 15;184(8):2212-2228.e12. doi: 10.1016/j.cell.2021.02.053. Epub 2021 Mar 2. Cell. 2021. PMID: 33713620 Free PMC article.

References

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1. Kragstrup T.W., Singh H.S., Grundberg I., Nielsen A.L.-L., Rivellese F., Mehta A., Goldberg M.B., Filbin M.R., Qvist P., Bibby B.M. Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients. PloS one. 2021;16 doi: 10.1371/journal.pone.0252799. - DOI - PMC - PubMed

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Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity

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Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity

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