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10.1016/j.bcp.2020.114122 http://scihub22266oqcxt.onion/10.1016/j.bcp.2020.114122 32592721!7314687!32592721     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32592721&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Biochem+Pharmacol 2020 ; 180 (ä): 114122 Nephropedia Template TP {{tp|p=32592721|t=2020. Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis |pdf=|usr=}}{{32592721}} gab.com Text Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis JO: Biochem Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32592721 #FOAvip An unprecedented biological function of natural cardenolides independent of their membrane target Na(+)/K(+)-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na(+)/K(+)-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na(+)/K(+)-ATPase alpha1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Herein, we further explored a Na(+)/K(+)-ATPase-independent signaling axis induced by natural cardenolides that also afforded significant anti-coronaviral activity for porcine TGEV and human HCoV-OC43. Using pharmacological inhibition and gene silencing techniques, we found that this anti-TGEV or anti-HCoV-OC43 activity was caused by JAK1 proteolysis and mediated through upstream activation of Ndfip1/2 and its effector NEDD4. This study provides novel insights into the pharmacological effects of natural cardenolides, and is expected to inform their future development as antiviral agents. Twit Text FOAVip Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis ????Biochem Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32592721 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32592721 #FOAvip English Wikipedia <ref>{{Cite pmid|32592721}}</ref> Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis #MMPMID32592721 Yang CW; Hsu HY; Chang HY; Lee YZ; Lee SJ Biochem Pharmacol 2020[Oct]; 180 (ä): 114122 PMID32592721show ga An unprecedented biological function of natural cardenolides independent of their membrane target Na(+)/K(+)-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na(+)/K(+)-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na(+)/K(+)-ATPase alpha1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Herein, we further explored a Na(+)/K(+)-ATPase-independent signaling axis induced by natural cardenolides that also afforded significant anti-coronaviral activity for porcine TGEV and human HCoV-OC43. Using pharmacological inhibition and gene silencing techniques, we found that this anti-TGEV or anti-HCoV-OC43 activity was caused by JAK1 proteolysis and mediated through upstream activation of Ndfip1/2 and its effector NEDD4. This study provides novel insights into the pharmacological effects of natural cardenolides, and is expected to inform their future development as antiviral agents. |Animals[MESH] |Antiviral Agents/*pharmacology[MESH] |Cardenolides/*pharmacology[MESH] |Carrier Proteins/metabolism[MESH] |Cell Line[MESH] |Coronavirus OC43, Human/*drug effects[MESH] |Down-Regulation/drug effects[MESH] |Female[MESH] |Gene Knockdown Techniques[MESH] |Humans[MESH] |Janus Kinase 1/*metabolism[MESH] |Leupeptins[MESH] |Membrane Proteins/metabolism[MESH] |Mice[MESH] |Mice, Inbred BALB C[MESH] |Nedd4 Ubiquitin Protein Ligases/metabolism[MESH] |Ouabain/pharmacology[MESH] |Phosphorylation[MESH] |Protease Inhibitors/pharmacology[MESH] |Proteolysis[MESH] |STAT1 Transcription Factor/metabolism[MESH] |STAT3 Transcription Factor/metabolism[MESH] |Signal Transduction/drug effects[MESH] |Sodium-Potassium-Exchanging ATPase/*metabolism[MESH] |Swine[MESH] |Transmissible gastroenteritis virus/*drug effects[MESH]Natural cardenolides suppress coronaviral replication by downregulatin(epmc).pdf DeepDyve Pubget Overpricing