{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:21:11Z","timestamp":1788639671509,"version":"build-2803163510"},"reference-count":283,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (\u22482 Euro\/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.<\/jats:p>","DOI":"10.3390\/ijms25137209","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-9401","authenticated-orcid":false,"given":"Juan-Fernando","family":"Pad\u00edn","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, School of Medicine at Ciudad Real, University of Castilla-La Mancha, 13971 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-6273","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"P\u00e9rez-Ortiz","sequence":"additional","affiliation":[{"name":"Facultad HM de Ciencias de la Salud, Universidad Camilo Jos\u00e9 Cela, 28692 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria HM Hospitales, 28015 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-0154","authenticated-orcid":false,"given":"Francisco Javier","family":"Redondo-Calvo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Medicine at Ciudad Real, University of Castilla-La Mancha, 13971 Ciudad Real, Spain"},{"name":"Department of Anaesthesiology and Critical Care Medicine, University General Hospital, 13005 Ciudad Real, Spain"},{"name":"Translational Research Unit, University General Hospital and Research Institute of Castilla-La Mancha (IDISCAM), 13005 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1055\/s-0028-1119811","article-title":"Healthcare-Associated Atypical Pneumonia","volume":"30","author":"Forgie","year":"2009","journal-title":"Semin. 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