| |  Online-Ressource |
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| Verfasst von: | Laise, Pasquale [VerfasserIn]  |
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| | Stanifer, Megan [VerfasserIn] |
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| | Bosker, Gideon [VerfasserIn] |
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| | Sun, Xiaoyun [VerfasserIn] |
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| | Triana, Sergio [VerfasserIn] |
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| | Doldan, Patricio [VerfasserIn] |
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| | La Manna, Federico [VerfasserIn] |
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| | De Menna, Marta [VerfasserIn] |
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| | Realubit, Ronald B. [VerfasserIn] |
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| | Pampou, Sergey [VerfasserIn] |
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| | Karan, Charles [VerfasserIn] |
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| | Alexandrov, Theodore [VerfasserIn] |
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| | Kruithof-de Julio, Marianna [VerfasserIn] |
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| | Califano, Andrea [VerfasserIn] |
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| | Boulant, Steeve [VerfasserIn] |
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| | Alvarez, Mariano J. [VerfasserIn] |
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| Titel: | A model for network-based identification and pharmacological targeting of aberrant, replication-permissive transcriptional programs induced by viral infection |
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| Verf.angabe: | Pasquale Laise, Megan L. Stanifer, Gideon Bosker, Xiaoyun Sun, Sergio Triana, Patricio Doldan, Federico La Manna, Marta De Menna, Ronald B. Realubit, Sergey Pampou, Charles Karan, Theodore Alexandrov, Marianna Kruithof-de Julio, Andrea Califano, Steeve Boulant & Mariano J. Alvarez |
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| E-Jahr: | 2022 |
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| Jahr: | 19 July 2022 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 22.02.2023 |
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| Titel Quelle: | Enthalten in: Communications biology |
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| Ort Quelle: | London : Springer Nature, 2018 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 5(2022) vom: Juli, Artikel-ID 714, Seite 1-12 |
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| ISSN Quelle: | 2399-3642 |
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| Abstract: | SARS-CoV-2 hijacks the host cell transcriptional machinery to induce a phenotypic state amenable to its replication. Here we show that analysis of Master Regulator proteins representing mechanistic determinants of the gene expression signature induced by SARS-CoV-2 in infected cells revealed coordinated inactivation of Master Regulators enriched in physical interactions with SARS-CoV-2 proteins, suggesting their mechanistic role in maintaining a host cell state refractory to virus replication. To test their functional relevance, we measured SARS-CoV-2 replication in epithelial cells treated with drugs predicted to activate the entire repertoire of repressed Master Regulators, based on their experimentally elucidated, context-specific mechanism of action. Overall, 15 of the 18 drugs predicted to be effective by this methodology induced significant reduction of SARS-CoV-2 replication, without affecting cell viability. This model for host-directed pharmacological therapy is fully generalizable and can be deployed to identify drugs targeting host cell-based Master Regulator signatures induced by virtually any pathogen. |
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| DOI: | doi:10.1038/s42003-022-03663-8 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1038/s42003-022-03663-8 |
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| | Volltext: https://www.nature.com/articles/s42003-022-03663-8 |
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| | DOI: https://doi.org/10.1038/s42003-022-03663-8 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Regulatory networks |
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| | Systems virology |
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| | Viral host response |
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| K10plus-PPN: | 1837294968 |
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| Verknüpfungen: | → Zeitschrift |
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¬A¬ model for network-based identification and pharmacological targeting of aberrant, replication-permissive transcriptional programs induced by viral infection / Laise, Pasquale [VerfasserIn]; 19 July 2022 (Online-Ressource)
