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10.1038/s41422-020-0356-z http://scihub22266oqcxt.onion/10.1038/s41422-020-0356-z 32541865!7294525!32541865     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 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Cell+Res 2020 ; 30 (8): 678-692 Nephropedia Template TP {{tp|p=32541865|t=2020. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease |pdf=|usr=}}{{32541865}} gab.com Text Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease JO: Cell Res http://www.kidney.de/pget.php?&tw=1&pmid=32541865 #FOAvip A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 microM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. Twit Text FOAVip Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease ????Cell Res http://www.kidney.de/pget.php?&tw=1&pmid=32541865 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32541865 #FOAvip English Wikipedia <ref>{{Cite pmid|32541865}}</ref> Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease #MMPMID32541865 Ma C; Sacco MD; Hurst B; Townsend JA; Hu Y; Szeto T; Zhang X; Tarbet B; Marty MT; Chen Y; Wang J Cell Res 2020[Aug]; 30 (8): 678-692 PMID32541865show ga A new coronavirus SARS-CoV-2, also called novel coronavirus 2019 (2019-nCoV), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.35% as of May 26, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 microM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 A resolution with three protomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics. |A549 Cells[MESH] |Animals[MESH] |Antiviral Agents/chemistry/*pharmacology[MESH] |Betacoronavirus/*enzymology[MESH] |COVID-19[MESH] |Caco-2 Cells[MESH] |Chlorocebus aethiops[MESH] |Coronavirus 3C Proteases[MESH] |Coronavirus Infections/*metabolism/virology[MESH] |Cysteine Endopeptidases/chemistry/metabolism[MESH] |Drug Discovery/methods[MESH] |Glycoproteins/*pharmacology[MESH] |Humans[MESH] |Inhibitory Concentration 50[MESH] |Kinetics[MESH] |Pandemics[MESH] |Pneumonia, Viral/*metabolism/virology[MESH] |Proline/*analogs & derivatives/pharmacology[MESH] |Protein Conformation[MESH] |Pyrrolidines/chemistry/*pharmacology[MESH] |SARS-CoV-2[MESH] |Sulfonic Acids[MESH] |Vero Cells[MESH] |Viral Nonstructural Proteins/*antagonists & inhibitors/chemistry/metabolism[MESH]Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 (epmc).pdf DeepDyve Pubget Overpricing