{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:58:43Z","timestamp":1778623123383,"version":"3.51.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T00:00:00Z","timestamp":1616889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35 HL140018"],"award-info":[{"award-number":["R35 HL140018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018535","name":"Cotswold Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018535","id-type":"DOI","asserted-by":"crossref"}]},{"name":"WW Smith endowed chair"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has given rise to the devastating global pandemic. In most cases, SARS-CoV-2 infection results in the development of viral pneumonia and acute respiratory distress syndrome, known as \u2018coronavirus disease 2019\u2019 or COVID-19. Intriguingly, besides the respiratory tract, COVID-19 affects other organs and systems of the human body. COVID-19 patients with pre-existing cardiovascular disease have a higher risk of death, and SARS-CoV-2 infection itself may cause myocardial inflammation and injury. One possible explanation of such phenomena is the fact that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor required for viral entry. ACE2 is expressed in the cells of many organs, including the heart. ACE2 functions as a carboxypeptidase that can cleave several endogenous substrates, including angiotensin II, thus regulating blood pressure and vascular tone. It remains largely unknown if the SARS-CoV-2 infection alters the enzymatic properties of ACE2, thereby contributing to cardiovascular complications in patients with COVID-19. Here, we demonstrate that ACE2 cleavage of des-Arg9-bradykinin substrate analogue is markedly accelerated, while cleavage of angiotensin II analogue is minimally affected by the binding of spike protein. These findings may have implications for a better understanding of COVID-19 pathogenesis.<\/jats:p>","DOI":"10.1093\/jb\/mvab041","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T20:10:08Z","timestamp":1616789408000},"page":"299-306","source":"Crossref","is-referenced-by-count":19,"title":["SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2"],"prefix":"10.1093","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8720-5062","authenticated-orcid":false,"given":"Anna A","family":"Kiseleva","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard,Philadelphia, PA 19104 , USA"},{"name":"Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania; 1157 BRB II\/III, 421 Curie Boulevard, Philadelphia, PA 19104 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M","family":"Troisi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania; 3610 Hamilton Walk, Philadelphia, PA 19104 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott E","family":"Hensley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania; 3610 Hamilton Walk, Philadelphia, PA 19104 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul M","family":"Kohli","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard,Philadelphia, PA 19104 , USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania; 242 Anatomy-Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA 19104 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard,Philadelphia, PA 19104 , USA"},{"name":"Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania; 1157 BRB II\/III, 421 Curie Boulevard, Philadelphia, PA 19104 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,28]]},"reference":[{"key":"2022100311583662100_mvab041-B1","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.3201\/eid1011.040797_02","article-title":"SARS, the first pandemic of the 21st century","volume":"10","author":"LeDuc","year":"2004","journal-title":"Emerg. 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