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10.1371/journal.pbio.3001490 http://scihub22266oqcxt.onion/10.1371/journal.pbio.3001490 34962926!8741300!34962926     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+Biol 2021 ; 19 (12): e3001490 Nephropedia Template TP {{tp|p=34962926|t=2021. A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets |pdf=|usr=}}{{34962926}} gab.com Text A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets JO: PLoS Biol http://www.kidney.de/pget.php?&tw=1&pmid=34962926 #FOAvip Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs. Twit Text FOAVip A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets ????PLoS Biol http://www.kidney.de/pget.php?&tw=1&pmid=34962926 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34962926 #FOAvip English Wikipedia <ref>{{Cite pmid|34962926}}</ref> A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets #MMPMID34962926 Kratzel A; Kelly JN; V'kovski P; Portmann J; Bruggemann Y; Todt D; Ebert N; Shrestha N; Plattet P; Staab-Weijnitz CA; von Brunn A; Steinmann E; Dijkman R; Zimmer G; Pfaender S; Thiel V PLoS Biol 2021[Dec]; 19 (12): e3001490 PMID34962926show ga Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs. |*CRISPR-Cas Systems[MESH] |Antiviral Agents/pharmacology[MESH] |Autophagy/*genetics[MESH] |Gene Knockdown Techniques[MESH] |Host-Pathogen Interactions[MESH] |Humans[MESH] |Middle East Respiratory Syndrome Coronavirus/drug effects/*genetics/physiology[MESH] |SARS-CoV-2/drug effects/*genetics/physiology[MESH]A genome-wide CRISPR screen identifies interactors of the autophagy pa(epmc).pdf DeepDyve Pubget Overpricing