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10.1038/s41467-021-24007-w http://scihub22266oqcxt.onion/10.1038/s41467-021-24007-w 34155207!8217552!34155207     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2021 ; 12 (1): 3818 Nephropedia Template TP {{tp|p=34155207|t=2021. SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals |pdf=|usr=}}{{34155207}} gab.com Text SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34155207 #FOAvip Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC(50) values of 136.7, 7.67, 0.11, and 0.13 muM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19. Twit Text FOAVip SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34155207 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34155207 #FOAvip English Wikipedia <ref>{{Cite pmid|34155207}}</ref> SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals #MMPMID34155207 Gassen NC; Papies J; Bajaj T; Emanuel J; Dethloff F; Chua RL; Trimpert J; Heinemann N; Niemeyer C; Weege F; Honzke K; Aschman T; Heinz DE; Weckmann K; Ebert T; Zellner A; Lennarz M; Wyler E; Schroeder S; Richter A; Niemeyer D; Hoffmann K; Meyer TF; Heppner FL; Corman VM; Landthaler M; Hocke AC; Morkel M; Osterrieder N; Conrad C; Eils R; Radbruch H; Giavalisco P; Drosten C; Muller MA Nat Commun 2021[Jun]; 12 (1): 3818 PMID34155207show ga Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC(50) values of 136.7, 7.67, 0.11, and 0.13 muM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19. |Animals[MESH] |Antinematodal Agents/pharmacology[MESH] |Autophagosomes/metabolism[MESH] |Autophagy[MESH] |Autophagy-Related Proteins/metabolism[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/*metabolism/pathology/*virology[MESH] |Cells, Cultured[MESH] |Chlorocebus aethiops[MESH] |Cricetinae[MESH] |Disease Models, Animal[MESH] |Humans[MESH] |Lung/metabolism/pathology/virology[MESH] |Metabolome[MESH] |Niclosamide/pharmacology[MESH] |Organoids[MESH] |SARS-CoV-2/isolation & purification/*metabolism[MESH] |Spermidine/pharmacology[MESH]SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers(epmc).pdf DeepDyve Pubget Overpricing