{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:55:20Z","timestamp":1777971320049,"version":"3.51.4"},"reference-count":109,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["No.2016YFC0904900"],"award-info":[{"award-number":["No.2016YFC0904900"]}]},{"name":"National Natural Science Foundation of PR China","award":["No.81973320"],"award-info":[{"award-number":["No.81973320"]}]},{"name":"National Natural Science Foundation of PR China","award":["No.81673509"],"award-info":[{"award-number":["No.81673509"]}]},{"name":"National Natural Science Foundation of PR China","award":["No.81573504"],"award-info":[{"award-number":["No.81573504"]}]},{"name":"National Natural Science Foundation of PR China","award":["No.81903714"],"award-info":[{"award-number":["No.81903714"]}]},{"DOI":"10.13039\/501100004826","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["No.7171012"],"award-info":[{"award-number":["No.7171012"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["No.7204317"],"award-info":[{"award-number":["No.7204317"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific research fund of Peking University First Hospital","award":["No.2019SF05"],"award-info":[{"award-number":["No.2019SF05"]}]},{"name":"Scientific research fund of Peking University First Hospital","award":["No.2019CR19"],"award-info":[{"award-number":["No.2019CR19"]}]},{"name":"Macau Science and Technology Development fund","award":["FDCT 067\/2018\/A2"],"award-info":[{"award-number":["FDCT 067\/2018\/A2"]}]},{"name":"Macau Science and Technology Development fund","award":["FDCT 033\/2017\/AMJ"],"award-info":[{"award-number":["FDCT 033\/2017\/AMJ"]}]},{"name":"Macau Science and Technology Development fund","award":["FDCT 0007\/2019\/AKP"],"award-info":[{"award-number":["FDCT 0007\/2019\/AKP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>December 2019 saw the emergence of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has spread across the globe. The high infectivity and ongoing mortality of SARS-CoV-2 emphasize the demand of drug discovery. Angiotensin-converting enzyme II (ACE2) is the functional receptor for SARS-CoV-2 entry into host cells. ACE2 exists as a membrane-bound protein on major viral target pulmonary epithelial cells, and its peptidase domain (PD) interacts SARS-CoV-2 spike protein with higher affinity. Therefore, targeting ACE2 is an important pharmacological intervention for a SARS-CoV-2 infection. In this review, we described the two-way switch role of ACE2 in the treatment of novel coronavirus pneumonia and underlying comorbidities, and discussed the potential effect of the ACE inhibitor and angiotensin receptor blocker on a hypertension patient with the SARS-CoV-2 infection. In addition, we analyzed the S-protein-binding site on ACE2 and suggested that blocking hot spot-31 and hot spot-353 on ACE2 could be a therapeutic strategy for preventing the spread of SARS-CoV-2. Besides, the recombinant ACE2 protein could be another potential treatment option for SARS-CoV-2 induced acute severe lung failure. This review could provide beneficial information for the development of anti-SARS-CoV-2 agents via targeting ACE2 and the clinical usage of renin-angiotensin system (RAS) drugs for novel coronavirus pneumonia treatment.<\/jats:p>","DOI":"10.3390\/molecules26010142","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T10:10:37Z","timestamp":1609409437000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Two-Way Switch Role of ACE2 in the Treatment of Novel Coronavirus Pneumonia and Underlying Comorbidities"],"prefix":"10.3390","volume":"26","author":[{"given":"Xiao Cong","family":"Pang","sequence":"first","affiliation":[{"name":"School of Pharmacy and State Key Laboratory for the Quality Research of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China"},{"name":"Department of Pharmacy, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suguro","family":"Rinkiko","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory for the Quality Research of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-1005","authenticated-orcid":false,"given":"Yi Min","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Zhun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory for the Quality Research of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China"},{"name":"Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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