{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:54:20Z","timestamp":1790470460161,"version":"4.1.0"},"reference-count":152,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin\u2013angiotensin system (RAS) in favor of the ACE\u2013angiotensin II (Ang II)\u2013angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II\u2013AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1\/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK\/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.<\/jats:p>","DOI":"10.3390\/molecules27072048","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T23:30:23Z","timestamp":1647991823000},"page":"2048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"George","family":"El-Arif","sequence":"first","affiliation":[{"name":"Faculty of Sciences 2, Department of Biology, Lebanese University, Campus Fanar, Jdeidet El-Matn, Beirut P.O. Box 90656, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa","family":"Khazaal","sequence":"additional","affiliation":[{"name":"Faculty of Sciences 3, Department of Biology, Lebanese University, Campus Michel Slayman Ras Maska, Tripoli 1352, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Farhat","sequence":"additional","affiliation":[{"name":"Faculty of Sciences 2, Department of Biology, Lebanese University, Campus Fanar, Jdeidet El-Matn, Beirut P.O. Box 90656, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Harb","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Sciences, University of Balamand, Dekouene Campus, Sin El Fil P.O. Box 55251, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-8109","authenticated-orcid":false,"given":"C\u00e9dric","family":"Annweiler","sequence":"additional","affiliation":[{"name":"Research Center on Autonomy and Longevity, Department of Geriatric Medicine and Memory Clinic, 44312 Angers, France"},{"name":"Laboratoire de Psychologie des Pays de la Loire, LPPL EA 4638, SFR Confluences, University of Angers, 44312 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingliang","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6509-4210","authenticated-orcid":false,"given":"Herv\u00e9","family":"Kovacic","sequence":"additional","affiliation":[{"name":"Institut de Neurophysiopathologie (INP), Aix-Marseille Universit\u00e9 CNRS, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-7467","authenticated-orcid":false,"given":"Ziad","family":"Abi Khattar","sequence":"additional","affiliation":[{"name":"Faculty of Sciences 2, Department of Biology, Lebanese University, Campus Fanar, Jdeidet El-Matn, Beirut P.O. Box 90656, Lebanon"},{"name":"Laboratory of Georesources, Geosciences and Environment (L2GE), Microbiology\/Tox-Ecotoxicology Team, Faculty of Sciences 2, Lebanese University, Campus Fanar, Jdeidet El-Matn, Beirut P.O. Box 90656, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Faculty of Sciences 3, Department of Biology, Lebanese University, Campus Michel Slayman Ras Maska, Tripoli 1352, Lebanon"},{"name":"Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-5647","authenticated-orcid":false,"given":"Jean-Marc","family":"Sabatier","sequence":"additional","affiliation":[{"name":"Institut de Neurophysiopathologie (INP), Aix-Marseille Universit\u00e9 CNRS, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An Overview of Their Replication and Pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Coronaviruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40203-020-00058-7","article-title":"Are losartan and imatinib effective against SARS-CoV-2 pathogenesis? 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