{"doi":"10.1371/journal.pone.0302436","title":"Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC","abstract":"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+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ 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 αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC 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 〈ENaC 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.","journal":"PLoS ONE","year":2024,"id":497004,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1343936,"name":"Erika Moreno","orcid":null,"position":1,"is_corresponding":false},{"id":1343713,"name":"Consuelo Plata","orcid":"0000-0001-9340-8950","position":2,"is_corresponding":false},{"id":675496,"name":"Héctor Carbajal‐Contreras","orcid":"0000-0001-5392-5929","position":3,"is_corresponding":false},{"id":675494,"name":"Adrián Rafael Murillo‐de‐Ozores","orcid":"0000-0003-0053-4662","position":4,"is_corresponding":false},{"id":1343937,"name":"Kevin García-Ávila","orcid":null,"position":5,"is_corresponding":false},{"id":903737,"name":"Norma Vázquez","orcid":"0000-0002-5265-9929","position":6,"is_corresponding":false},{"id":1343938,"name":"Maria Syed","orcid":null,"position":7,"is_corresponding":false},{"id":227844,"name":"Jan Wysocki","orcid":"0000-0002-8429-272X","position":8,"is_corresponding":false},{"id":227843,"name":"Daniel Batlle","orcid":"0000-0002-5878-9046","position":9,"is_corresponding":false},{"id":468993,"name":"Gerardo Gamba","orcid":"0000-0002-4378-9043","position":10,"is_corresponding":false},{"id":675497,"name":"María Castañeda‐Bueno","orcid":"0000-0002-5801-3504","position":11,"is_corresponding":false},{"id":903736,"name":"Germán Magaña-Ávila","orcid":"0000-0002-1486-1173","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:09:30.779495Z","pmid":"38662786","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}