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10.1021/acs.jmedchem.0c01063 http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.0c01063 33054210!ä!33054210 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 Deprecated: Implicit conversion from float 267.2 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 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Med+Chem 2020 ; 63 (21): 12725-12747 Nephropedia Template TP {{tp|p=33054210|t=2020. Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 |pdf=|usr=}}{{33054210}} gab.com Text Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=33054210 #FOAvip The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CL(pro)) in a post-translational processing step that is critical for coronavirus replication. The 3CL(pro) sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CL(pro) employing ligand-protease structures solved by X-ray crystallography led to the identification of 3 and 4. Preclinical experiments reveal 4 (PF-00835231) as a potent inhibitor of CoV-2 3CL(pro) with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19. Twit Text FOAVip Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=33054210 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33054210 #FOAvip English Wikipedia <ref>{{Cite pmid|33054210}}</ref> Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19 #MMPMID33054210 Hoffman RL; Kania RS; Brothers MA; Davies JF; Ferre RA; Gajiwala KS; He M; Hogan RJ; Kozminski K; Li LY; Lockner JW; Lou J; Marra MT; Mitchell LJ Jr; Murray BW; Nieman JA; Noell S; Planken SP; Rowe T; Ryan K; Smith GJ 3rd; Solowiej JE; Steppan CM; Taggart B J Med Chem 2020[Nov]; 63 (21): 12725-12747 PMID33054210show ga The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CL(pro)) in a post-translational processing step that is critical for coronavirus replication. The 3CL(pro) sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CL(pro) employing ligand-protease structures solved by X-ray crystallography led to the identification of 3 and 4. Preclinical experiments reveal 4 (PF-00835231) as a potent inhibitor of CoV-2 3CL(pro) with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19. |Animals[MESH] |Antiviral Agents/chemical synthesis/metabolism/*pharmacology[MESH] |COVID-19 Drug Treatment[MESH] |Catalytic Domain[MESH] |Chlorocebus aethiops[MESH] |Coronavirus 3C Proteases/*antagonists & inhibitors/chemistry/metabolism[MESH] |Crystallography, X-Ray[MESH] |Humans[MESH] |Ketones/chemical synthesis/metabolism/*pharmacology[MESH] |Protease Inhibitors/chemical synthesis/metabolism/*pharmacology[MESH] |Protein Binding[MESH] |SARS-CoV-2/*drug effects[MESH]Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Prote(epmc).pdf DeepDyve Pubget Overpricing