{"id":393,"date":"2022-10-19T15:54:00","date_gmt":"2022-10-19T15:54:00","guid":{"rendered":"https:\/\/boulantlab.com\/?post_type=publications&#038;p=393"},"modified":"2022-10-26T15:58:00","modified_gmt":"2022-10-26T15:58:00","slug":"a-model-for-network-based-identification-and-pharmacological-targeting-of-aberrant-replication-permissive-transcriptional-programs-induced-by-viral-infection","status":"publish","type":"publications","link":"https:\/\/boulantlab.com\/publications\/a-model-for-network-based-identification-and-pharmacological-targeting-of-aberrant-replication-permissive-transcriptional-programs-induced-by-viral-infection\/","title":{"rendered":"A model for network-based identification and pharmacological targeting of aberrant, replication-permissive transcriptional programs induced by viral infection"},"content":{"rendered":"\n<p>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.<\/p>\n","protected":false},"featured_media":394,"template":"","_links":{"self":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications\/393"}],"collection":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/types\/publications"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media\/394"}],"wp:attachment":[{"href":"https:\/\/boulantlab.com\/wp-json\/wp\/v2\/media?parent=393"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}