{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:54:18Z","timestamp":1777492458159,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007801","name":"Fundaci\u00f3n Seneca","doi-asserted-by":"publisher","award":["Project 00002\/COVI\/20"],"award-info":[{"award-number":["Project 00002\/COVI\/20"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad Cat\u00f3lica San Antonio de Murcia","award":["FURINHICOVID"],"award-info":[{"award-number":["FURINHICOVID"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.<\/jats:p>","DOI":"10.3390\/ijms23052796","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T09:24:53Z","timestamp":1646299493000},"page":"2796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7330-7597","authenticated-orcid":false,"given":"David","family":"Zaragoza-Huesca","sequence":"first","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Mart\u00ednez-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Cat\u00f3lica de Murcia, 30107 Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Jes\u00fas","family":"Banegas-Luna","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Cat\u00f3lica de Murcia, 30107 Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"P\u00e9rez-Garrido","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Cat\u00f3lica de Murcia, 30107 Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josefina Mar\u00eda","family":"Vegara-Meseguer","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Cat\u00f3lica de Murcia, 30107 Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Pe\u00f1as-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carmen","family":"Rodenas","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Esp\u00edn","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-7898","authenticated-orcid":false,"given":"Horacio","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, UCAM Universidad Cat\u00f3lica de Murcia, 30107 Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-6464","authenticated-orcid":false,"given":"Irene","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, CIBERER, Universidad de Murcia, IMIB-Arrixaca, 30003 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1073","DOI":"10.1002\/cti2.1073","article-title":"Furin-mediated protein processing in infectious diseases and cancer","volume":"8","author":"Braun","year":"2019","journal-title":"Clin. 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