{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:47Z","timestamp":1787029247421,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Piano di Sostegno alla Ricerca UNIMI","award":["Linea 2"],"award-info":[{"award-number":["Linea 2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell\/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial properties, but less is known about its antiviral effects. We performed in vitro studies to investigate the antiviral and anti-inflammatory activity of erdosteine in A549-hACE2 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) and in Caco-2 human colon carcinoma cells infected with influenza A virus (H1N1). The cells were treated with different concentrations of erdosteine or its active metabolite 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MET-1) before and after viral infection. The viral replication\/load in the cell culture supernatants was measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay and digital droplet PCR. The gene expression of innate immune response signaling pathways and oxidative stress was analyzed by reverse transcription PCR custom-array. The results showed that erdosteine and its active metabolite, at concentrations consistent with an approved therapeutic human dosage, were not directly cytotoxic and had significant antiviral effects in cells pre-infected with SARS-CoV-2, RSV, and H1N1. The transcriptome analysis showed that erdosteine activated innate immune responses by stimulating overexpression of type I interferon and inflammasome pathways and modulated oxidative stress by inducing the modulation of oxidative stress and GSH pathways. These findings suggest that erdosteine may be a useful treatment for respiratory viral infections.<\/jats:p>","DOI":"10.3390\/pathogens14040388","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T10:49:54Z","timestamp":1744714194000},"page":"388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antiviral Effect of Erdosteine in Cells Infected with Human Respiratory Viruses"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-8253","authenticated-orcid":false,"given":"Pierachille","family":"Santus","sequence":"first","affiliation":[{"name":"Division of Respiratory Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, 20147 Milan, Italy"},{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-4523","authenticated-orcid":false,"given":"Sergio","family":"Strizzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiammetta","family":"Danzo","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, 20147 Milan, Italy"},{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3671-4235","authenticated-orcid":false,"given":"Mara","family":"Biasin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-2503","authenticated-orcid":false,"given":"Irma","family":"Saulle","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-6675","authenticated-orcid":false,"given":"Claudia","family":"Vanetti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences (DIBIC), Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Saad","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Ospedale L. 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