{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:15:51Z","timestamp":1778285751608,"version":"3.51.4"},"reference-count":111,"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\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK114855 and NS123649"],"award-info":[{"award-number":["DK114855 and NS123649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This review summarizes the seminal studies that informed current efforts to inhibit furin. These include the convergent efforts of endocrinologists, virologists, and yeast geneticists that, together, culminated in the discovery of furin. We describe the pioneering biochemical studies which led to the first furin inhibitors that were able to block the disease pathways which are broadly critical for pathogen virulence, tumor invasiveness, and atherosclerosis. We then summarize how these studies subsequently informed current strategies leading to the development of small-molecule furin inhibitors as potential therapies to combat SARS-CoV-2 and other diseases that rely on furin for their pathogenicity and progression.<\/jats:p>","DOI":"10.3390\/ijms23073435","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"3435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2"],"prefix":"10.3390","volume":"23","author":[{"given":"Gary","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Couture","sequence":"additional","affiliation":[{"name":"TransBIOTech, L\u00e9vis, QC G6V 6Z3, Canada"},{"name":"Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada"},{"name":"Centre de Recherche du Centre Int\u00e9gr\u00e9 de Sant\u00e9 et de Services Sociaux de Chaudi\u00e8re-Appalaches, L\u00e9vis, QC G6V 3Z1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-3680","authenticated-orcid":false,"given":"Anna","family":"Kwiatkowska","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie de Sherbrooke, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrm934","article-title":"Furin at the cutting edge: From protein traffic to embryogenesis and disease","volume":"3","author":"Thomas","year":"2002","journal-title":"Nat. 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