Cellular host factors for SARS-CoV-2 infection DOI Creative Commons
Jim Baggen, Els Vanstreels, Sander Jansen

et al.

Nature Microbiology, Journal Year: 2021, Volume and Issue: 6(10), P. 1219 - 1232

Published: Sept. 1, 2021

The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives and caused a global economic crisis. No effective antiviral drugs are currently available to treat infections severe acute respiratory syndrome 2 (SARS-CoV-2). medical need imposed by the spurred unprecedented research efforts study biology. Every virus depends on cellular host factors pathways for successful replication. These proviral represent attractive targets therapy as they genetically more stable than viral may be shared among related viruses. application various 'omics' technologies led rapid discovery that required completion SARS-CoV-2 life cycle. In this Review, we summarize insights into infection were mainly obtained using functional genetic interactome screens. We discuss processes important cycle, well parallels with non-coronaviruses. Finally, highlight could targeted clinically approved molecules in clinical trials potential therapies COVID-19. Proviral infection, replication COVID-19 reviewed.

Language: Английский

The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions DOI Creative Commons
Rose Oughtred,

Jennifer Rust,

Christie Chang

et al.

Protein Science, Journal Year: 2020, Volume and Issue: 30(1), P. 187 - 200

Published: Oct. 18, 2020

The BioGRID (Biological General Repository for Interaction Datasets, thebiogrid.org) is an open-access database resource that houses manually curated protein and genetic interactions from multiple species including yeast, worm, fly, mouse, human. ~1.93 million in can be used to build complex networks facilitate biomedical discoveries, particularly as related human health disease. All content primary experimental evidence the literature, includes both focused low-throughput studies large high-throughput datasets. also captures post-translational modifications or gene with bioactive small molecules many known drugs. A built-in network visualization tool combines all annotations allows users generate graphs of protein, chemical interactions. In addition general curation across species, undertakes themed projects specific aspects cellular regulation, example ubiquitin-proteasome system, well disease areas, such SARS-CoV-2 virus causes COVID-19 severe acute respiratory syndrome. recent extension BioGRID, named Open CRISPR Screens (ORCS, orcs.thebiogrid.org), single mutant phenotypes published high throughput genome-wide CRISPR/Cas9-based screens. BioGRID-ORCS contains datasets over 1,042 screens carried out date human, mouse fly cell lines. research community freely access data through web interface, standardized file downloads, via model organism databases partner meta-databases.

Language: Английский

Citations

1231

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 DOI Creative Commons
Camila Rosat Consiglio, Nicola Cotugno,

Fabian Sardh

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(4), P. 968 - 981.e7

Published: Sept. 6, 2020

Summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication the rare multisystem inflammatory children (MIS-C) associated with COVID-19, presenting 4–6 weeks after as high fever, organ dysfunction, strongly elevated markers of inflammation. The pathogenesis unclear but has overlapping features Kawasaki disease suggestive vasculitis a likely autoimmune etiology. We apply systems-level analyses blood immune cells, cytokines, autoantibodies healthy children, enrolled prior to infected SARS-CoV-2, MIS-C. find that response MIS-C differs from cytokine storm severe shares several disease, also this condition respect T cell subsets, interleukin (IL)-17A, biomarkers arterial damage. Finally, autoantibody profiling suggests multiple could be involved

Language: Английский

Citations

846

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography DOI Creative Commons
Steffen Klein, Mirko Cortese, Sophie L. Winter

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 18, 2020

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID19 pandemic, is a highly pathogenic β-coronavirus. As other coronaviruses, SARS-CoV-2 enveloped, replicates in cytoplasm and assembles at intracellular membranes. Here, we structurally characterize viral replication compartment report critical insights into budding mechanism virus, structure extracellular virions close to their native state by situ cryo-electron tomography subtomogram averaging. We directly visualize RNA filaments inside double membrane vesicles, compartments associated with replication. The show diameter consistent double-stranded frequent branching likely representing secondary structures. that assembled S trimers lumenal cisternae do not alone induce bending but laterally reorganize on envelope during virion assembly. ribonucleoprotein complexes (vRNPs) are accumulated curved characteristic for sites suggesting vRNP recruitment enhanced curvature. Subtomogram averaging shows vRNPs distinct cylindrical assemblies. propose genome packaged around multiple separate complexes, thereby allowing incorporation unusually large while maintaining high steric flexibility between vRNPs.

Language: Английский

Citations

684

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms DOI Creative Commons
David E. Gordon, Joseph Hiatt, Mehdi Bouhaddou

et al.

Science, Journal Year: 2020, Volume and Issue: 370(6521)

Published: Oct. 15, 2020

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 closely related more lethal but less transmissible coronaviruses SARS-CoV-1 Middle East (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on proliferation, including Tom70, mitochondrial chaperone interacts with both ORF9b, an structurally characterized using cryo-electron microscopy. Combining genetically validated patient data medical billing records molecular mechanisms potential drug treatments merit further clinical study.

Language: Английский

Citations

682

Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells DOI Creative Commons
Zharko Daniloski, Tristan X. Jordan, Hans‐Hermann Wessels

et al.

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 92 - 105.e16

Published: Oct. 24, 2020

Language: Английский

Citations

571

Liquid–liquid phase separation in human health and diseases DOI Creative Commons
Bin Wang, Lei Zhang, Tong Dai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 1, 2021

Abstract Emerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences indicate LLPS plays role human health diseases. In this review, we describe our current understanding summarize its physiological functions. We further development Additionally, review recently developed methods for studying LLPS. Although research is infancy—but fast-growing—it clear an essential pathophysiological conditions. This highlights need overview recent advances field to translate knowledge regarding into therapeutic discoveries.

Language: Английский

Citations

450

Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex DOI Creative Commons
James Chen, Brandon Malone, Eliza Llewellyn

et al.

Cell, Journal Year: 2020, Volume and Issue: 182(6), P. 1560 - 1573.e13

Published: July 28, 2020

Language: Английский

Citations

442

Diversity and versatility of p38 kinase signalling in health and disease DOI Open Access
Begoña Cánovas, Ángel R. Nebreda

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(5), P. 346 - 366

Published: Jan. 27, 2021

Language: Английский

Citations

432

Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses DOI Creative Commons
Ruofan Wang, Camille R. Simoneau, Jessie Kulsuptrakul

et al.

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 106 - 119.e14

Published: Dec. 9, 2020

Language: Английский

Citations

404

Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium DOI Creative Commons
Fadi Jacob, Sarshan R. Pather,

Wei‐Kai Huang

et al.

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(6), P. 937 - 950.e9

Published: Sept. 21, 2020

Language: Английский

Citations

396