Similar Datasets
Project description:Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its replication cycle. However, a detailed understanding of the interactions between the virus and the host cell is necessary in order to facilitate development of host-directed therapeutics. As a first step, we performed a genome-wide loss of function screen using the alphacoronavirus HCoV-229E to better define the interactions between coronaviruses and host factors. We report the identification and validation of an ER-resident host protein, TMEM41B, as an essential host factor for not only HCoV-229E but also genetically distinct coronaviruses including the pandemic betacoronavirus SARS-CoV-2. We show that the protein is required at an early, but post-receptor engagement, stage of the viral lifecycle. Further, mechanistic studies revealed that although the protein was not enriched at replication complexes, it likely contributes to viral replication complex formation via mobilization of cholesterol and other lipids to facilitate host membrane expansion and curvature. Continued study of TMEM41B and the development of approaches to prevent its function may lead to broad spectrum anti-coronavirus therapeutics.
| S-EPMC8189496 | biostudies-literature
Project description:TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2
| PRJNA670023 | ENA
Project description:We performed genome-wide CRISPR KO screens in human Huh7.5.1 cells to select for mutations that render host cells resistant to viral infection by SARS-CoV-2, human coronavirus 229E and OC43.
2020-10-16 | E-MTAB-9638 | biostudies-arrayexpress
Project description:Host-virus protein-protein interactions play key roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Further characterization of these interactions and comparison to other large-scale study of cellular responses to SARS-CoV-2 infection elucidated how distinct SARS-CoV-2 viral proteins participate in its lifecycle. With these data mining, we discovered potential drug targets for the treatment of COVID-19. The interactomes of two key SARS-CoV-2-encoded viral proteins, NSP1 and N, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of SARS-CoV-2 provides valuable resources for the understanding and treating of this disease.
| S-SCDT-EMBOJ-2021-107776 | biostudies-other
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19) in humans, which may be lethal. In this study, we used a comparative transcriptomics approach to investigate the effects of SARS-CoV-2 infection on the host mRNA and sRNA expression programs in two primate cell lines. Upon infection, we observed global changes in host gene expression and differential expression of dozens of host miRNAs, many with known links to viral infection and immune response. Unexpectedly, we also discovered an expanded landscape of more than a hundred SARS-CoV-2-derived small viral RNAs (svRNAs), predicted to interact with differentially expressed host mRNAs and miRNAs. svRNAs are derived from distinct regions of the viral genome and sequence signatures suggest they are produced by a non-canonical biogenesis pathway. Our data suggest that svRNAs may play a role in SARS-CoV-2 propagation and antagonization of these svRNAs has potential for use as a therapeutic target.
2022-03-01 | GSE197521 | GEO
Project description:Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human and murine β-coronaviruses. The potency of in-cell CSNK2A target engagement across the set of inhibitors correlated with antiviral activity and genetic knockdown confirmed the essential role of the CSNK2 holoenzyme in β-coronavirus replication. Spike protein uptake was blocked by CSNK2A inhibition, indicating that antiviral activity was due in part to a suppression of viral entry. CSNK2A inhibition may be a viable target for development of new broad spectrum anti-β-coronavirus drugs.Graphical abstract
| S-EPMC8750650 | biostudies-literature
Project description:Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs.
2021-06-24 | PXD021222 | Pride
Project description:Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.
| S-EPMC8675922 | biostudies-literature
Project description:The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is one of seven human coronaviruses. G-quadruplexes are intrinsic obstacles to genome replication. Whether G-quadruplexes are present in human coronaviruses is unknown. In the current study, we have predicted that all seven human coronaviruses harbor G-quadruplex sequences. Conserved G-quadruplex sequences in SARS-CoV and SARS-CoV-2 were analyzed and verified by circular dichroism (CD) spectroscopy and Thioflavin T fluorescence assay. Similar to SARS-CoV, SARS-CoV-2 encodes an nsP3 protein, which is predicted to associate with G-quadruplexes. Targeting G-quadruplex sequences in the SARS-CoV-2 genome by G-quadruplex ligands could be a new way to conquer COVID-19.
| S-EPMC7644843 | biostudies-literature
Project description:SARS-COV-2 caused COVID-19 has caused unprecedented global health crisis. Coronavirus have developed a variety of mechanisms to interfere host translation machinery to facilitate virus protein production. Here, we conducted Ribometh-seq to explore the effects of ectopic expression of SARS-COV-2 N protein on rRNA 2'-O-me modification profiles of host cells.
2022-10-28 | GSE199130 | GEO