{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:51Z","timestamp":1740146991192,"version":"3.37.3"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["101720"],"award-info":[{"award-number":["101720"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["A1-S-8290"],"award-info":[{"award-number":["A1-S-8290"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI166940-01"],"award-info":[{"award-number":["AI166940-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017622","name":"Feinberg Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007059","name":"Northwestern University","doi-asserted-by":"publisher","award":["COVID-19 Collaborative Innovation Award"],"award-info":[{"award-number":["COVID-19 Collaborative Innovation Award"]}],"id":[{"id":"10.13039\/100007059","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na<jats:sup>+<\/jats:sup> channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na<jats:sup>+<\/jats:sup> reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of \u03b1ENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and \u03b1ENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between \u2329ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.<\/jats:p>","DOI":"10.1371\/journal.pone.0302436","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T17:48:57Z","timestamp":1714067337000},"page":"e0302436","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC"],"prefix":"10.1371","volume":"19","author":[{"given":"Germ\u00e1n Ricardo","family":"Maga\u00f1a-\u00c1vila","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-8950","authenticated-orcid":true,"given":"Consuelo","family":"Plata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Carbajal-Contreras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian 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