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10.1038/s41467-021-25729-7 http://scihub22266oqcxt.onion/10.1038/s41467-021-25729-7 34535662!8448725!34535662     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=34535662&cmd=llinks): Failed to open stream: HTTP request failed! 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A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses |pdf=|usr=}}{{34535662}} gab.com Text A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34535662 #FOAvip Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses. Twit Text FOAVip A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34535662 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34535662 #FOAvip English Wikipedia <ref>{{Cite pmid|34535662}}</ref> A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses #MMPMID34535662 Beumer J; Geurts MH; Lamers MM; Puschhof J; Zhang J; van der Vaart J; Mykytyn AZ; Breugem TI; Riesebosch S; Schipper D; van den Doel PB; de Lau W; Pleguezuelos-Manzano C; Busslinger G; Haagmans BL; Clevers H Nat Commun 2021[Sep]; 12 (1): 5498 PMID34535662show ga Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses. |*Biological Specimen Banks[MESH] |*CRISPR-Cas Systems[MESH] |*Coronavirus[MESH] |Angiotensin-Converting Enzyme 2/*genetics[MESH] |COVID-19[MESH] |Cell Line[MESH] |Dipeptidyl Peptidase 4/*genetics[MESH] |Humans[MESH] |Middle East Respiratory Syndrome Coronavirus[MESH] |Organoids/*metabolism[MESH] |SARS-CoV-2[MESH] |Serine Endopeptidases/*genetics[MESH] |Transcriptome[MESH]A CRISPR/Cas9 genetically engineered organoid biobank reveals essentia(epmc).pdf DeepDyve Pubget Overpricing