Matches in SemOpenAlex for { <https://semopenalex.org/work/W4210651776> ?p ?o ?g. }
- W4210651776 abstract "Abstract Precise characterization and targeting of host cell transcriptional machinery hijacked by viral infection remains challenging. Here, we show that SARS-CoV-2 hijacks the host cell transcriptional machinery to induce a phenotypic state amenable to its replication. Specifically, analysis of Master Regulator (MR) proteins representing mechanistic determinants of the gene expression signature induced by SARS-CoV-2 in infected cells revealed coordinated inactivation of MRs 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 MRs, based on their experimentally elucidated, context-specific mechanism of action. Overall, >80% of 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 MR signatures induced by virtually any pathogen." @default.
- W4210651776 created "2022-02-08" @default.
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- W4210651776 date "2022-02-04" @default.
- W4210651776 modified "2023-09-26" @default.
- W4210651776 title "A Model for Network-Based Identification and Pharmacological Targeting of Aberrant, Replication-Permissive Transcriptional Programs Induced by Viral Infection" @default.
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- W4210651776 doi "https://doi.org/10.21203/rs.3.rs-1287631/v1" @default.
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