{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:46:00Z","timestamp":1774442760318,"version":"3.50.1"},"reference-count":192,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans\/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed. In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease.<\/jats:p>","DOI":"10.3390\/cells9071704","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T06:38:55Z","timestamp":1595313535000},"page":"1704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The Yin and Yang of ACE\/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-1026","authenticated-orcid":false,"given":"Loris","family":"Zamai","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino \u201cCarlo Bo\u201d, 61032 Urbino, Italy"},{"name":"INFN-Gran Sasso National Laboratory, Assergi, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, J.-J., Dong, X., Cao, Y.-Y., Yuan, Y.-D., Yang, Y.-B., Yan, Y.-Q., Akdis, C.A., and Gao, Y.-D. 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