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The most potent compound 4\u2010guanidinomethyl\u2010phenylacteyl\u2010Arg\u2010Tle\u2010Arg\u20104\u2010amidinobenzylamide (MI\u20101148) inhibits furin with a <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> value of 5.5\u2005p<jats:sc>M<\/jats:sc>. The derivatives also strongly inhibit PC1\/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI\u20101148 was crystallized in complex with human furin. Its N\u2010terminal guanidinomethyl group in the <jats:italic>para<\/jats:italic> position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the <jats:italic>meta<\/jats:italic> position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short\u2010term treatment of acute infectious diseases.<\/jats:p>","DOI":"10.1002\/cmdc.201500103","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T08:46:54Z","timestamp":1431593214000},"page":"1218-1231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Novel Furin Inhibitors with Potent Anti\u2010infectious Activity"],"prefix":"10.1002","volume":"10","author":[{"given":"Kornelia","family":"Hardes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gero L.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven O.","family":"Dahms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"K\u00f6hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Sandvig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Walz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"von\u2005Messling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel E.","family":"Than","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Garten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Steinmetzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,14]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm934"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3699"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1242\/dev.125.24.4863","volume":"125","author":"Roebroek A. 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