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@ARTICLE{Laise:180984,
author = {P. Laise and M. L. Stanifer and G. Bosker and X. Sun and S.
Triana and P. Doldan$^*$ and F. La Manna and M. De Menna and
R. B. Realubit and S. Pampou and C. Karan and T. Alexandrov
and M. Kruithof-de Julio and A. Califano and S. Boulant$^*$
and M. J. Alvarez},
title = {{A} model for network-based identification and
pharmacological targeting of aberrant,
replication-permissive transcriptional programs induced by
viral infection.},
journal = {Communications biology},
volume = {5},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2022-01708},
pages = {714},
year = {2022},
note = {Research Group “Cellular Polarity and ViralInfection”,
German Cancer Research Center (DKFZ), Heidelberg, Germany.},
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.},
keywords = {COVID-19: drug therapy / Humans / SARS-CoV-2 /
Transcriptome / Virus Diseases / Virus Replication},
cin = {F140},
ddc = {570},
cid = {I:(DE-He78)F140-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35854100},
pmc = {pmc:PMC9296638},
doi = {10.1038/s42003-022-03663-8},
url = {https://inrepo02.dkfz.de/record/180984},
}