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10.1007/s00018-021-04085-1 http://scihub22266oqcxt.onion/10.1007/s00018-021-04085-1 35013790!8747446!35013790     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 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cell+Mol+Life+Sci 2022 ; 79 (1): 65 Nephropedia Template TP {{tp|p=35013790|t=2022. The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses |pdf=|usr=}}{{35013790}} gab.com Text The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses JO: Cell Mol Life Sci http://www.kidney.de/pget.php?&tw=1&pmid=35013790 #FOAvip Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 million deaths to date. While vaccination is a powerful tool to control pandemic spread, medication to relieve COVID-19-associated symptoms and alleviate disease progression especially in high-risk patients is still lacking. In this study, we explore the suitability of the rapid accelerated fibrosarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway as a druggable target in the treatment of SARS-CoV-2 infections. We find that SARS-CoV-2 transiently activates Raf/MEK/ERK signaling in the very early infection phase and that ERK1/2 knockdown limits virus replication in cell culture models. We demonstrate that ATR-002, a specific inhibitor of the upstream MEK1/2 kinases which is currently evaluated in clinical trials as an anti-influenza drug, displays strong anti-SARS-CoV-2 activity in cell lines as well as in primary air-liquid-interphase epithelial cell (ALI) cultures, with a safe and selective treatment window. We also observe that ATR-002 treatment impairs the SARS-CoV-2-induced expression of pro-inflammatory cytokines, and thus might prevent COVID-19-associated hyperinflammation, a key player in COVID-19 progression. Thus, our data suggest that the Raf/MEK/ERK signaling cascade may represent a target for therapeutic intervention strategies against SARS-CoV-2 infections and that ATR-002 is a promising candidate for further drug evaluation. Twit Text FOAVip The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses ????Cell Mol Life Sci http://www.kidney.de/pget.php?&tw=1&pmid=35013790 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35013790 #FOAvip English Wikipedia <ref>{{Cite pmid|35013790}}</ref> The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses #MMPMID35013790 Schreiber A; Viemann D; Schoning J; Schloer S; Mecate Zambrano A; Brunotte L; Faist A; Schofbanker M; Hrincius E; Hoffmann H; Hoffmann M; Pohlmann S; Rescher U; Planz O; Ludwig S Cell Mol Life Sci 2022[Jan]; 79 (1): 65 PMID35013790show ga Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 million deaths to date. While vaccination is a powerful tool to control pandemic spread, medication to relieve COVID-19-associated symptoms and alleviate disease progression especially in high-risk patients is still lacking. In this study, we explore the suitability of the rapid accelerated fibrosarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway as a druggable target in the treatment of SARS-CoV-2 infections. We find that SARS-CoV-2 transiently activates Raf/MEK/ERK signaling in the very early infection phase and that ERK1/2 knockdown limits virus replication in cell culture models. We demonstrate that ATR-002, a specific inhibitor of the upstream MEK1/2 kinases which is currently evaluated in clinical trials as an anti-influenza drug, displays strong anti-SARS-CoV-2 activity in cell lines as well as in primary air-liquid-interphase epithelial cell (ALI) cultures, with a safe and selective treatment window. We also observe that ATR-002 treatment impairs the SARS-CoV-2-induced expression of pro-inflammatory cytokines, and thus might prevent COVID-19-associated hyperinflammation, a key player in COVID-19 progression. Thus, our data suggest that the Raf/MEK/ERK signaling cascade may represent a target for therapeutic intervention strategies against SARS-CoV-2 infections and that ATR-002 is a promising candidate for further drug evaluation. |*COVID-19 Drug Treatment[MESH] |A549 Cells[MESH] |Adult[MESH] |Animals[MESH] |Antiviral Agents/*pharmacology[MESH] |COVID-19/metabolism[MESH] |Cell Line[MESH] |Cells, Cultured[MESH] |Chlorocebus aethiops[MESH] |Cytokines/metabolism[MESH] |Fenamates/*pharmacology[MESH] |Humans[MESH] |Inflammation/drug therapy/metabolism[MESH] |MAP Kinase Kinase 1/antagonists & inhibitors/metabolism[MESH] |MAP Kinase Kinase 2/antagonists & inhibitors/metabolism[MESH] |MAP Kinase Signaling System/*drug effects[MESH] |Protein Kinase Inhibitors/*pharmacology[MESH] |SARS-CoV-2/*drug effects/physiology[MESH] |Vero Cells[MESH]The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation(epmc).pdf DeepDyve Pubget Overpricing