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10.1038/s41422-021-00519-4 http://scihub22266oqcxt.onion/10.1038/s41422-021-00519-4 34112954!8190750!34112954     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 265.2 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 Deprecated: Implicit conversion from float 265.2 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 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cell+Res 2021 ; 31 (8): 847-860 Nephropedia Template TP {{tp|p=34112954|t=2021. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target |pdf=|usr=}}{{34112954}} gab.com Text SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target JO: Cell Res http://www.kidney.de/pget.php?&tw=1&pmid=34112954 #FOAvip Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2. Twit Text FOAVip SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target ????Cell Res http://www.kidney.de/pget.php?&tw=1&pmid=34112954 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34112954 #FOAvip English Wikipedia <ref>{{Cite pmid|34112954}}</ref> SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target #MMPMID34112954 Xia B; Shen X; He Y; Pan X; Liu FL; Wang Y; Yang F; Fang S; Wu Y; Duan Z; Zuo X; Xie Z; Jiang X; Xu L; Chi H; Li S; Meng Q; Zhou H; Zhou Y; Cheng X; Xin X; Jin L; Zhang HL; Yu DD; Li MH; Feng XL; Chen J; Jiang H; Xiao G; Zheng YT; Zhang LK; Shen J; Li J; Gao Z Cell Res 2021[Aug]; 31 (8): 847-860 PMID34112954show ga Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2. |Angiotensin-Converting Enzyme 2/genetics[MESH] |Animals[MESH] |Antiviral Agents/chemistry/*metabolism/therapeutic use[MESH] |Apoptosis[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/complications/*pathology/virology[MESH] |Coronavirus Envelope Proteins/antagonists & inhibitors/genetics/*metabolism[MESH] |Cytokines/metabolism[MESH] |Disease Models, Animal[MESH] |Half-Life[MESH] |Humans[MESH] |Lung/metabolism/pathology[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Mice, Transgenic[MESH] |Mutagenesis, Site-Directed[MESH] |Respiratory Distress Syndrome/*etiology[MESH] |SARS-CoV-2/isolation & purification/*metabolism/pathogenicity[MESH] |Spleen/metabolism/pathology[MESH] |Viral Load[MESH]SARS-CoV-2 envelope protein causes acute respiratory distress syndrome(epmc).pdf DeepDyve Pubget Overpricing