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10.1038/s41586-021-03493-4 http://scihub22266oqcxt.onion/10.1038/s41586-021-03493-4 33845483!ä!33845483 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       Nature 2021 ; 594 (7862): 246-252 Nephropedia Template TP {{tp|p=33845483|t=2021. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV |pdf=|usr=}}{{33845483}} gab.com Text Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=33845483 #FOAvip The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology(1-10). Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-beta pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2. Twit Text FOAVip Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=33845483 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33845483 #FOAvip English Wikipedia <ref>{{Cite pmid|33845483}}</ref> Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV #MMPMID33845483 Stukalov A; Girault V; Grass V; Karayel O; Bergant V; Urban C; Haas DA; Huang Y; Oubraham L; Wang A; Hamad MS; Piras A; Hansen FM; Tanzer MC; Paron I; Zinzula L; Engleitner T; Reinecke M; Lavacca TM; Ehmann R; Wolfel R; Jores J; Kuster B; Protzer U; Rad R; Ziebuhr J; Thiel V; Scaturro P; Mann M; Pichlmair A Nature 2021[Jun]; 594 (7862): 246-252 PMID33845483show ga The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology(1-10). Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-beta pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2. |*Host-Pathogen Interactions/immunology[MESH] |*Proteomics[MESH] |Animals[MESH] |Antiviral Agents/pharmacology[MESH] |Autophagy/drug effects[MESH] |COVID-19/immunology/*metabolism/virology[MESH] |Cell Line[MESH] |Datasets as Topic[MESH] |Drug Evaluation, Preclinical[MESH] |Humans[MESH] |Matrix Metalloproteinase Inhibitors/pharmacology[MESH] |Phosphorylation[MESH] |Protein Interaction Maps[MESH] |Protein Kinase Inhibitors/pharmacology[MESH] |Protein Processing, Post-Translational[MESH] |Proteome/chemistry/*metabolism[MESH] |SARS-CoV-2/immunology/*pathogenicity[MESH] |Severe Acute Respiratory Syndrome/immunology/*metabolism/virology[MESH] |Severe acute respiratory syndrome-related coronavirus/immunology/*pathogenicity[MESH] |Transforming Growth Factor beta/metabolism[MESH] |Ubiquitination[MESH] |Viral Proteins/chemistry/metabolism[MESH]Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SAR(epmc).pdf DeepDyve Pubget Overpricing