Evidence map›Paper›PMID 35854100›Full record

ArticleCommunications biology2022

A model for network-based identification and pharmacological targeting of aberrant, replication-permissive transcriptional programs induced by viral infection.

Pasquale Laise, Megan L Stanifer, Gideon Bosker, Xiaoyun Sun, Sergio Triana, Patricio Doldan, Federico La Manna, Marta De Menna, Ronald B Realubit, Sergey Pampou and 6 more

Abstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Organoids: physiologically relevantJournal of virology · 2025
    Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Pasquale Laise *DarwinHealth Inc, New York, NY, USA.
Megan L Stanifer *Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Heidelberg, Germany.
Gideon BoskerDarwinHealth Inc, New York, NY, USA.
Xiaoyun SunDarwinHealth Inc, New York, NY, USA.
Sergio TrianaStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Patricio DoldanDepartment of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
Federico La MannaDepartment for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland.
Marta De MennaDepartment for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland.
Ronald B RealubitDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Sergey PampouDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Charles KaranDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Theodore AlexandrovStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Marianna Kruithof-de JulioDepartment for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland.ORCID 0000-0002-6085-7706
Andrea CalifanoDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. ac2248@cumc.columbia.edu.ORCID 0000-0003-4742-3679
Steeve BoulantDepartment of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, FL, USA. s.boulant@ufl.edu.
Mariano J AlvarezDarwinHealth Inc, New York, NY, USA. malvarez@darwinhealth.com.ORCID 0000-0002-7503-2491

Funding

Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Systematic Identification and Pharmacological Targeting of Tumor Dependencies for Precision Cancer MedicineU01CA217858 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2017 to 2021
$6.1M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
NCI NIH HHS R35 CA197745NCI NIH HHS U01 CA217858NIH HHS S10 OD012351NIH HHS S10 OD021764
6 · The paper itself

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.

Indexed as

COVID-19 Drug TreatmentVirus DiseasesHumansSARS-CoV-2TranscriptomeVirus Replication

Identifiers

PMID35854100
PMCPMC9296638

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.