Similar Datasets
Project description:To search for host factors regulating SARS-COV-2 infection, we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid human ESCs. The regulators were identified by the quantification of enrichment of their mutant clones within a pooled loss-of-function library upon SARS-COV-2 infection.
2023-08-09 | E-MTAB-12505 | biostudies-arrayexpress
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:Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that can cause severe respiratory disease in humans. Identification of the host factors that are necessary for viral infection and virus-induced cell death is critical to our understanding of the viral life cycle and can potentially aid the development of new treatment options. Here, we report CRISPR screen results of both SARS-CoV and MERS-CoV infections in derivatives of the human hepatoma cell line Huh7. Our screens identified the known entry receptors ACE2 for SARS-CoV and DPP4 for MERS-CoV. Additionally, the SARS-CoV screen uncovered several components of the NF-κB signaling pathway (CARD10, BCL10, MALT1, MAP3K7, IKBKG), while the MERS-CoV screen revealed the polypyrimidine tract-binding protein PTBP1, the ER scramblase TMEM41B, furin protease and several transcriptional and chromatin regulators as candidate factors for viral replication and/or virus-induced cell death. Together, we present several known and unknown coronavirus host factors that are of interest for further investigation.
2024-01-08 | GSE252396 | GEO
Project description:Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. A genome-wide CRISPR screen with SARS-CoV-2 was performed in Vero-E6 cells (data not provided here), identifying known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.
2020-10-05 | GSE154761 | GEO
Project description:To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells. Top-ranked genes cluster into distinct pathways, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. We validate these gene targets using several orthogonal methods such as CRISPR knock-out, RNA interference knock-down, and small-molecule inhibitors. Using single-cell RNA- sequencing, we identify shared transcriptional changes in cholesterol biosynthesis upon loss of top-ranked genes. In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells. Overall, this work provides a genome- scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.
2020-10-24 | GSE159519 | GEO
Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.
| 12454 | ecrin-mdr-crc
Project description:Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 in Vero-E6 cells, identifying known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.
2020-10-05 | GSE154782 | GEO
Project description:Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 in Vero-E6 cells, identifying known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex, the alarmin HMGB1, and the transcription factors Smad3 and Smad4. Small molecule inhibitors of these pathways inhibited SARS-CoV-2-infection in both monkey and human cells, demonstrating the conserved role of these genetic hits across species. We also revealed that HMGB1 is a novel regulator of ACE2 expression and critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.
2020-10-05 | GSE154783 | GEO
Project description:Anti-viral host factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill this gap, we performed a genome-wide CRISPR dropout screen and integrated analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-seq, and host-host/viral protein-protein/RNA interactome. We identified many anti-viral host genes that were missed by previous studies, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that inhibited viral entry/replication. We also identified the cohesin complex as a novel antiviral pathway, supporting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discovered an anti-viral transcription factor KLF5, a regulator of sphingolipid metabolism, which was up-regulated and harbored genetic variations linked to COVID-19 patients with severe symptoms. Our analyses provide a resource for understanding the host antiviral network for combating SARS-CoV-2 and may help develop new therapeutic strategies.
2023-08-08 | GSE209750 | GEO
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