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10.1038/s41467-021-24156-y http://scihub22266oqcxt.onion/10.1038/s41467-021-24156-y 34162861!8222394!34162861     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 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       Nat+Commun 2021 ; 12 (1): 3907 Nephropedia Template TP {{tp|p=34162861|t=2021. A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry |pdf=|usr=}}{{34162861}} gab.com Text A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34162861 #FOAvip SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection. Twit Text FOAVip A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=34162861 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34162861 #FOAvip English Wikipedia <ref>{{Cite pmid|34162861}}</ref> A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry #MMPMID34162861 Chen Y; Lear TB; Evankovich JW; Larsen MB; Lin B; Alfaras I; Kennerdell JR; Salminen L; Camarco DP; Lockwood KC; Tuncer F; Liu J; Myerburg MM; McDyer JF; Liu Y; Finkel T; Chen BB Nat Commun 2021[Jun]; 12 (1): 3907 PMID34162861show ga SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection. |*COVID-19 Drug Treatment[MESH] |Angiotensin-Converting Enzyme 2/metabolism[MESH] |Animals[MESH] |COVID-19/metabolism/pathology/virology[MESH] |Cells, Cultured[MESH] |Chlorocebus aethiops[MESH] |High-Throughput Screening Assays/methods[MESH] |Homoharringtonine/*pharmacology[MESH] |Humans[MESH] |Lung/drug effects/metabolism/pathology/virology[MESH] |Mice[MESH] |Piperidines/*pharmacology[MESH] |Protein Synthesis Inhibitors/pharmacology[MESH] |Quinazolinones/*pharmacology[MESH] |SARS-CoV-2/*drug effects/isolation & purification/*physiology[MESH] |Serine Endopeptidases/*metabolism[MESH] |Spike Glycoprotein, Coronavirus/metabolism[MESH]A high-throughput screen for TMPRSS2 expression identifies FDA-approve(epmc).pdf DeepDyve Pubget Overpricing