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10.1038/s41467-020-20718-8 http://scihub22266oqcxt.onion/10.1038/s41467-020-20718-8 33473130!7817691!33473130     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 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       Nat+Commun 2021 ; 12 (1): 488 Nephropedia Template TP {{tp|p=33473130|t=2021. The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery |pdf=|usr=}}{{33473130}} gab.com Text The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=33473130 #FOAvip SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC(50) of 2.1 muM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLpro(C111S) in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro. Twit Text FOAVip The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=33473130 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33473130 #FOAvip English Wikipedia <ref>{{Cite pmid|33473130}}</ref> The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery #MMPMID33473130 Fu Z; Huang B; Tang J; Liu S; Liu M; Ye Y; Liu Z; Xiong Y; Zhu W; Cao D; Li J; Niu X; Zhou H; Zhao YJ; Zhang G; Huang H Nat Commun 2021[Jan]; 12 (1): 488 PMID33473130show ga SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC(50) of 2.1 muM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLpro(C111S) in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro. |*COVID-19 Drug Treatment[MESH] |Antiviral Agents/*chemistry/*pharmacology[MESH] |COVID-19/metabolism/virology[MESH] |Coronavirus 3C Proteases/*chemistry/genetics/metabolism[MESH] |Cytokines/metabolism[MESH] |Drug Discovery[MESH] |Drug Interactions[MESH] |HEK293 Cells[MESH] |High-Throughput Screening Assays[MESH] |Humans[MESH] |Inhibitory Concentration 50[MESH] |Models, Molecular[MESH] |Pandemics[MESH] |Protein Conformation[MESH] |SARS-CoV-2/*drug effects/genetics/metabolism[MESH]The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot sp(epmc).pdf DeepDyve Pubget Overpricing