ACE2: The Major Cell Entry Receptor for SARS-CoV-2

A novel coronavirus from patients with pneumonia in China, 2019

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286 · see citing works

Factors associated with COVID-19-related death using OpenSAFELY

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Origin and evolution of pathogenic coronaviruses

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Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

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A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9

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Angiotensin-converting enzyme 2 protects from severe acute lung failure

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Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

Zou, X., Chen, K., Zou, J., Han, P., Hao, J., & Han, Z. (2020) · Frontiers of Medicine · doi:10.1007/s11684-020-0754-0 · Cited by 2,287 · see citing works

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues

Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, Y., Yousif, A. S., Bals, J., Hauser, B. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.035 · Cited by 2,284 · see citing works

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

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A Human Homolog of Angiotensin-converting Enzyme

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Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

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Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2

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TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein

Heurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O., & Pöhlmann, S. (2013) · Journal of Virology · doi:10.1128/jvi.02202-13 · Cited by 882 · see citing works

ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19

Leung, J. M., Yang, C. X., Tam, A., Shaipanich, T., Hackett, T., Singhera, G. K., Dorscheid, D. R., & Sin, D. D. (2020) · European Respiratory Journal · doi:10.1183/13993003.00688-2020 · Cited by 865 · see citing works

Tumor Necrosis Factor-α Convertase (ADAM17) Mediates Regulated Ectodomain Shedding of the Severe-acute Respiratory Syndrome-Coronavirus (SARS-CoV) Receptor, Angiotensin-converting Enzyme-2 (ACE2)

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A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry

Shulla, A., Heald-Sargent, T. A., Subramanya, G., Zhao, J., Perlman, S. M., & Gallagher, T. (2010) · Journal of Virology · doi:10.1128/jvi.02062-10 · Cited by 686 · see citing works

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome

Khan, A., Benthin, C., Zeno, B. R., Albertson, T. E., Boyd, J. H., Christie, J. D., Hall, R., Poirier, G., Ronco, J. J., Tidswell, M., et al. (2017) · Critical Care · doi:10.1186/s13054-017-1823-x · Cited by 600 · see citing works

Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2

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Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry

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Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63

Glowacka, I., Bertram, S., Herzog, P., Pfefferle, S., Steffen, I., Muench, M. O., Simmons, G., Hofmann, H., Kuri, T., Weber, F., et al. (2009) · Journal of Virology · doi:10.1128/jvi.01248-09 · Cited by 495 · see citing works

ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome

Devaux, C. A., Rolain, J., & Raoult, D. (2020) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2020.04.015 · Cited by 477 · see citing works

Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?

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COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids

Peters, M. C., Sajuthi, S. P., DeFord, P., Christenson, S. A., Rios, C. L., Montgomery, M. T., Woodruff, P. G., Mauger, D. T., ERZURUM, S. C., Johansson, M. W., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202003-0821oc · Cited by 444 · see citing works

Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice

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Role of the renin–angiotensin system in vascular inflammation

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COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

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Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract

Smith, J. C., Sausville, E. L., Girish, V., Yuan, M. L., Vasudevan, A., John, K. M., & Sheltzer, J. M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.05.012 · Cited by 414 · see citing works

The angiotensin–converting enzyme gene family: genomics and pharmacology

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ACE2, Much More Than Just a Receptor for SARS-COV-2

Samavati, L., & Uhal, B. D. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00317 · Cited by 366 · see citing works

Pharmacokinetics and Pharmacodynamics of Recombinant Human Angiotensin-Converting Enzyme 2 in Healthy Human Subjects

Haschke, M., Schuster, M., Poglitsch, M., Loibner, H., Salzberg, M. O., Bruggisser, M., Penninger, J. M., & Krähenbühl, S. (2013) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0072-7 · Cited by 362 · see citing works

Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells

Kimura, H., Francisco, D., Conway, M., Martínez, F. D., Vercelli, D., Polverino, F., Billheimer, D. D., & Kraft, M. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.05.004 · Cited by 340 · see citing works

Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration

Sodhi, C. P., Wohlford-Lenane, C., Yamaguchi, Y., Prindle, T., Fulton, W. B., Wang, S., McCray, P. B., Chappell, M. C., Hackam, D. J., & Jia, H. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00498.2016 · Cited by 333 · see citing works

Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray

Childs, R. A., Palma, A. S., Wharton, S. A., Matrosovich, T. Y., Liu, Y., Chai, W., Campanero‐Rhodes, M. A., Zhang, Y.-B., Eickmann, M., Kiso, M., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt0909-797 · Cited by 330 · see citing works

Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia

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Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis

Chun, H. J., Ali, Z. A., Kojima, Y., Kundu, R. K., Sheikh, A. Y., Agrawal, R., Zheng, L., Leeper, N. J., Pearl, N., Patterson, A. J., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34871 · Cited by 329 · see citing works

Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China

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Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome

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Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker

Furuhashi, M., Moniwa, N., Mita, T., Fuseya, T., Ishimura, S., Ohno, K., Shibata, S., Tanaka, M., Watanabe, Y. S., Akasaka, H., et al. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpu086 · Cited by 263 · see citing works

Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor

Onabajo, O. O., Banday, A. R., Stanifer, M. L., Yan, W., Obajemu, A., Santer, D. M., Florez-Vargas, O., Piontkivska, H., Vargas, J. M., Ring, T. J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00731-9 · Cited by 261 · see citing works

ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population

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ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

Lee, I. T., Nakayama, T., Wu, C.-T., Goltsev, Y., Jiang, S., Gall, P. A., Liao, S. C., Shih, L., Schürch, C. M., McIlwain, D. R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19145-6 · Cited by 253 · see citing works

Detection of Soluble Angiotensin-Converting Enzyme 2 in Heart Failure

Epelman, S., Tang, W. H. W., Chen, S. Y., Lente, F. V., Francis, G. S., & Sen, S. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.02.088 · Cited by 251 · see citing works

AT2 receptors: Functional relevance in cardiovascular disease

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COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children

Ciaglia, E., Vecchione, C., & Puca, A. A. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.00206 · Cited by 232 · see citing works

SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule

Wérion, A., Belkhir, L., Perrot, M., Schmit, G., Aydın, S., Chen, Z., Penaloza, A., Greef, J. D., Yıldız, H., Pothen, L., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.07.019 · Cited by 232 · see citing works

Increased ACE 2 and Decreased ACE Protein in Renal Tubules From Diabetic Mice

Ye, M., Wysocki, J. A., Naaz, P., Salabat, M. R., LaPointe, M. S., & BATLLE, D. C. (2004) · Hypertension · doi:10.1161/01.hyp.0000126192.27644.76 · Cited by 221 · see citing works

Increasing host cellular receptor—angiotensin‐converting enzyme 2 expression by coronavirus may facilitate 2019‐nCoV (or SARS‐CoV‐2) infection

Zhuang, M., Cheng, Y., Zhang, J., Jiang, X., Wang, L., Deng, J., & Wang, P. (2020) · Journal of Medical Virology · doi:10.1002/jmv.26139 · Cited by 212 · see citing works

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

Cholankeril, G. T., Podboy, A. J., Aivaliotis, V. I., Tarlow, B., Pham, E. A., Spencer, S. P., Kim, D., Hsing, A. W., & Ahmed, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.04.008 · Cited by 208 · see citing works

Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent

Serfözö, P. D., Wysocki, J. A., Gulua, G., Schulze, A., Ye, M., Liu, P., Jin, J., Bäder, M., Myöhänen, T. T., Garcia-Horsman, A., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.14071 · Cited by 198 · see citing works

Apelin is a positive regulator of ACE2 in failing hearts

Sato, T., SUZUKI, T. A., Watanabe, H., Kadowaki, A., Fukamizu, A., Liu, P. P., Kimura, A., Ito, H., Penninger, J. M., Imai, Y., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69608 · Cited by 188 · see citing works

Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor

Davidson, A. M., Wysocki, J. A., & BATLLE, D. C. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.15256 · Cited by 180 · see citing works

Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?

Perrotta, F., Matera, M. G., Cazzola, M., & Bianco, A. (2020) · Respiratory Medicine · doi:10.1016/j.rmed.2020.105996 · Cited by 178 · see citing works

Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress

Clarke, N. E., Belyaev, N. D., Lambert, D., & Turner, A. J. (2013) · Clinical Science · doi:10.1042/cs20130291 · Cited by 169 · see citing works

Understanding the renin–angiotensin–aldosterone–SARS-CoV axis: a comprehensive review

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What’s new in the renin-angiotensin system?

Warner, F. J., Smith, A. I., Hooper, N. M., & Turner, A. J. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4240-7 · Cited by 153 · see citing works

Current smoking is not associated with COVID-19

Rossato, M., Russo, L., Mazzocut, S., Vincenzo, A. D., Fioretto, P., & Vettor, R. (2020) · European Respiratory Journal · doi:10.1183/13993003.01290-2020 · Cited by 147 · see citing works

The apelin receptor inhibits the angiotensin II type 1 receptor via allosteric trans‐inhibition

Siddiquee, K., Hampton, J., McAnally, D., May, L. T., & Smith, L. H. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02192.x · Cited by 141 · see citing works

Calmodulin interacts with angiotensin‐converting enzyme‐2 (ACE2) and inhibits shedding of its ectodomain

Lambert, D., Clarke, N. E., Hooper, N. M., & Turner, A. J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.085 · Cited by 131 · see citing works

TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds

Haga, S., Nagata, N., Okamura, T., Yamamoto, N., Sata, T., Yamamoto, N., Sasazuki, T., & Ishizaka, Y. (2009) · Antiviral Research · doi:10.1016/j.antiviral.2009.12.001 · Cited by 130 · see citing works

A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells

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Age and sex differences in soluble ACE2 may give insights for COVID-19

Swärd, P., Edsfeldt, A., Reepalu, A., Jehpsson, L., Rosengren, B. E., & Karlsson, M. K. (2020) · Critical Care · doi:10.1186/s13054-020-02942-2 · Cited by 121 · see citing works

The plasma kallikrein-kinin system counterbalances the renin-angiotensin system

Schmaier, A. H. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15490 · Cited by 115 · see citing works

Angiotensin receptor subtype AT1 mediates alveolar epithelial cell apoptosis in response to ANG II

Papp, M., Li, X., Zhuang, J., Wang, R., & Uhal, B. D. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00103.2001 · Cited by 115 · see citing works

Angiotensin II–Dependent Superoxide

Welch, W. J. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.090472 · Cited by 109 · see citing works

Plasma ACE2 Activity Predicts Mortality in Aortic Stenosis and Is Associated With Severe Myocardial Fibrosis

Ramchand, J., Patel, S. K., Kearney, L. G., Matalanis, G. S., Farouque, O., Srivastava, P., & Burrell, L. M. (2019) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2019.09.005 · Cited by 105 · see citing works

Angiotensin A/Alamandine/MrgD Axis: Another Clue to Understanding Cardiovascular Pathophysiology

Hrenak, J., Paulis, L., & Šimko, F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071098 · Cited by 101 · see citing works

Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421

Lambert, D., Lambert, L. A., Clarke, N. E., Hooper, N. M., Porter, K. E., & Turner, A. J. (2014) · Clinical Science · doi:10.1042/cs20130420 · Cited by 96 · see citing works

Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects

Jacobs, M., Eeckhoutte, H. P. V., Wijnant, S. R. A., Janssens, W., Joos, G., Brusselle, G., & Bracke, K. R. (2020) · European Respiratory Journal · doi:10.1183/13993003.02378-2020 · Cited by 93 · see citing works

Decoy ACE2-expressing extracellular vesicles that competitively bind SARS-CoV-2 as a possible COVID-19 therapy

Inal, J. M. (2020) · Clinical Science · doi:10.1042/cs20200623 · Cited by 84 · see citing works

The kinin–kallikrein system: physiological roles, pathophysiology and its relationship to cancer biomarkers

Kashuba, E., Bailey, J. R., Allsup, D. J., & Cawkwell, L. (2013) · Biomarkers · doi:10.3109/1354750x.2013.787544 · Cited by 80 · see citing works

Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule–1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity

Whiteman, S. C., Bianco, A., Knight, R. A., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m205329200 · Cited by 79 · see citing works

Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2

Mathewson, A. C., Bishop, A., Yao, Y., Kemp, F., Ren, J., Chen, H., Xu, X., Berkhout, B., van der Hoek, L., & Jones, I. M. (2008) · Journal of General Virology · doi:10.1099/vir.0.2008/003962-0 · Cited by 79 · see citing works

Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents

Irham, L. M., Chou, W., Calkins, M. J., Adikusuma, W., Hsieh, S.-L. E., & Chang, W. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.179 · Cited by 78 · see citing works

Kinin B1 receptors as a therapeutic target for inflammation

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Plasma levels of soluble ACE2are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19

Kornilov, S. A., Lucas, I., Jade, K., et al. (2020) · Critical Care · doi:10.1186/s13054-020-03141-9 · Cited by 75 · see citing works

Different cross-talk sites between the renin–angiotensin and the kallikrein–kinin systems

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Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection?

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COVID-19 and coagulative axis: review of emerging aspects in a novel disease

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