Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.

SUBMITTER: Schneider WM

PROVIDER: S-EPMC7796900 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

Project description:The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS- CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan- coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.

2020-11-24 | GSE162038 | GEO

Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

Project description:Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

| PRJNA680344 | ENA

The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.

Project description: Not available

| S-EPMC3203193 | biostudies-literature

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities.

Project description: Not available

| S-EPMC8605023 | biostudies-literature

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

Project description: Not available

| S-EPMC7808408 | biostudies-literature

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 disease specific mechanisms and vulnerabilities.

Project description:Coronaviruses constitute a constant threat as documented by the recent emergence of SARS-CoV-2 that has caused more than 2,5 million deaths worldwide. Despite this our understanding of coronaviruses and how they interact with their host is very limited. Here we describe a novel phage display library for the discovery of viral short linear interaction motifs (SLiMs) from RNA viruses that mediate binding to human host factors. We utilize this library to uncover the unique patterns of viral SLiMs mediating SARS-CoV-2 - host factor interactions. This established a specific interaction between the human G3BP1/2 proteins and an xFG peptide motif in the viral nucleocapside (N) protein that when disrupted reduce viral replication and infection. We show that the N protein through this xFG motif modulates the G3BP1/2 host interactome by competing with numerous cellular xFG containing proteins and inhibits G3BP1/2 mediated stress granule formation. Collectively our work outlines a strategy for system-wide understanding of viral-host factor interactions that provides both mechanistic insight and pinpoints therapeutically relevant interactions for development of novel antiviral strategies.

2021-10-29 | PXD025410 | Pride

Comparative Host-Coronavirus Protein Interaction Networks Reveal Pan-Viral Disease Mechanisms

Project description:Abstract: The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, has highlighted emergent viruses as significant threats to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. We find that proteins often do not change localization across viruses but their sequence divergence dictates differences in host interactions. Functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryoEM. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms (IL-17 regulation) and drug treatments (sigma-1 receptor ligands) that merit further molecular and clinical study.

2020-10-16 | PXD021588 | Pride

Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-19 | GSE169113 | GEO

Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication [PigGeCKO]

Project description:We use the a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library (Zhao et al., 2020) to identify key host factors facilitating TGEV infection in porcine cells.

2021-11-19 | GSE169111 | GEO

Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

Project description:The ongoing SARS-CoV-2 pandemic has devastated the global economy and claimed more than one million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures (33 ºC and 37 ºC) along with three related coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution relative to genome scale studies. This approach yielded several new insights, including unexpected virus-specific differences in Rab GTPase requirements and GPI anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating COVID-19, and help prepare for future coronavirus outbreaks.

2020-11-24 | GSE162039 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data