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10.1016/j.jbc.2021.100701 http://scihub22266oqcxt.onion/10.1016/j.jbc.2021.100701 33895135!8062550!33895135     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 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2021 ; 296 (ä): 100701 Nephropedia Template TP {{tp|p=33895135|t=2021. Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells |pdf=|usr=}}{{33895135}} gab.com Text Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33895135 #FOAvip The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [(14)C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019. Twit Text FOAVip Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=33895135 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33895135 #FOAvip English Wikipedia <ref>{{Cite pmid|33895135}}</ref> Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells #MMPMID33895135 Carpinteiro A; Gripp B; Hoffmann M; Pohlmann S; Hoertel N; Edwards MJ; Kamler M; Kornhuber J; Becker KA; Gulbins E J Biol Chem 2021[Jan]; 296 (ä): 100701 PMID33895135show ga The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [(14)C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019. |Administration, Inhalation[MESH] |Ambroxol/*pharmacology[MESH] |Animals[MESH] |Antiviral Agents/*pharmacology[MESH] |Biological Transport[MESH] |Ceramides/metabolism[MESH] |Chlorocebus aethiops[MESH] |Drug Repositioning[MESH] |Epithelial Cells/drug effects/enzymology/virology[MESH] |Expectorants[MESH] |Gene Expression[MESH] |Humans[MESH] |Primary Cell Culture[MESH] |Reassortant Viruses/drug effects/physiology[MESH] |SARS-CoV-2/*drug effects/physiology[MESH] |Sphingomyelin Phosphodiesterase/antagonists & inhibitors/*genetics/metabolism[MESH] |Sphingomyelins/metabolism[MESH] |Spike Glycoprotein, Coronavirus/genetics/metabolism[MESH] |Vero Cells[MESH] |Vesiculovirus/*drug effects/physiology[MESH]Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 en(epmc).pdf DeepDyve Pubget Overpricing