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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,5,28]]},"abstract":"<jats:p>New therapeutic strategies targeting influenza are actively sought due to limitations in current drugs available. Host-directed therapy is an emerging concept to target host functions involved in pathogen life cycles and\/or pathogenesis, rather than pathogen components themselves. From this perspective, we focused on an essential host partner of influenza viruses, the RED\u2013SMU1 splicing complex. Here, we identified two synthetic molecules targeting an \u03b1-helix\/groove interface essential for RED\u2013SMU1 complex assembly. We solved the structure of the SMU1 N-terminal domain in complex with RED or bound to one of the molecules identified to disrupt this complex. We show that these compounds inhibiting RED\u2013SMU1 interaction also decrease endogenous RED-SMU1 levels and inhibit viral mRNA splicing and viral multiplication, while preserving cell viability. Overall, our data demonstrate the potential of RED-SMU1 destabilizing molecules as an antiviral therapy that could be active against a wide range of influenza viruses and be less prone to drug resistance.<\/jats:p>","DOI":"10.1073\/pnas.1901214116","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T20:19:28Z","timestamp":1557519568000},"page":"10968-10977","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["Destabilization of the human RED\u2013SMU1 splicing complex as a basis for host-directed antiinfluenza strategy"],"prefix":"10.1073","volume":"116","author":[{"given":"Usama","family":"Ashraf","sequence":"first","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire des Virus \u00e0 ARN, D\u00e9partement de Virologie, Institut Pasteur, 75015 Paris, France;"},{"name":"UMR 3569, Centre National de la Recherche Scientifique (CNRS), 75015 Paris, France;"},{"name":"Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot EA302, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tengo","sequence":"additional","affiliation":[{"name":"Institut de Biologie Structurale (IBS), Universit\u00e9 Grenoble-Alpes (UGA), Commissariat \u00e0 l\u2019Energie Atomique et aux Energies Alternatives (CEA), CNRS, 38044 Grenoble, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Le Corre","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Equipe Synth\u00e8se Organique pour la Recherche Biom\u00e9dicale, Universit\u00e9 Paris Descartes, CNRS UMR 8601, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Fournier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire des Virus \u00e0 ARN, D\u00e9partement de Virologie, Institut Pasteur, 75015 Paris, France;"},{"name":"UMR 3569, Centre National de la Recherche Scientifique (CNRS), 75015 Paris, France;"},{"name":"Sorbonne Paris Cit\u00e9, Universit\u00e9 Paris Diderot EA302, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Busca","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Equipe Synth\u00e8se Organique pour la Recherche Biom\u00e9dicale, Universit\u00e9 Paris Descartes, CNRS UMR 8601, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL) Grenoble, 38042 Grenoble, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Anne","family":"Rameix-Welti","sequence":"additional","affiliation":[{"name":"UMR1173, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Versailles St. Quentin, 78180 Montigny-le-Bretonneux, France;"},{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, Laboratoire de Microbiologie, H\u00f4pital Ambroise Par\u00e9, 92100 Boulogne-Billancourt, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gravier-Pelletier","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Equipe Synth\u00e8se Organique pour la Recherche Biom\u00e9dicale, Universit\u00e9 Paris Descartes, CNRS UMR 8601, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob W. 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