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10.1016/j.cbi.2020.109348 http://scihub22266oqcxt.onion/10.1016/j.cbi.2020.109348 33278462!7710351!33278462     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Chem+Biol+Interact 2021 ; 335 (ä): 109348 Nephropedia Template TP {{tp|p=33278462|t=2021. 2-Pyridone natural products as inhibitors of SARS-CoV-2 main protease |pdf=|usr=}}{{33278462}} gab.com Text 2-Pyridone natural products as inhibitors of SARS-CoV-2 main protease JO: Chem Biol Interact http://www.kidney.de/pget.php?&tw=1&pmid=33278462 #FOAvip The disease, COVID-19, is caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) for which there is currently no treatment. The SARS-CoV-2 main protease (M(pro)) is an important enzyme for viral replication. Small molecules that inhibit this protease could lead to an effective COVID-19 treatment. The 2-pyridone scaffold was previously identified as a possible key pharmacophore to inhibit SARS-CoV-2 M(pro). A search for natural, antimicrobial products with the 2-pyridone moiety was undertaken herein, and their calculated potency as inhibitors of SARS-CoV-2 M(pro) was investigated. Thirty-three natural products containing the 2-pyridone scaffold were identified from the literature. An in silico methodology using AutoDock was employed to predict the binding energies and inhibition constants (K(i) values) for each 2-pyridone-containing compound with SARS-CoV-2 M(pro). This consisted of molecular optimization of the 2-pyridone compound, docking of the compound with a crystal structure of SARS-CoV-2 M(pro), and evaluation of the predicted interactions and ligand-enzyme conformations. All compounds investigated bound to the active site of SARS-CoV-2 M(pro), close to the catalytic dyad (His-41 and Cys-145). Thirteen molecules had predicted K(i) values <1 muM. Glu-166 formed a key hydrogen bond in the majority of the predicted complexes, while Met-165 had some involvement in the complex binding as a close contact to the ligand. Prominent 2-pyridone compounds were further evaluated for their ADMET properties. This work has identified 2-pyridone natural products with calculated potent inhibitory activity against SARS-CoV-2 M(pro) and with desirable drug-like properties, which may lead to the rapid discovery of a treatment for COVID-19. Twit Text FOAVip 2-Pyridone natural products as inhibitors of SARS-CoV-2 main protease ????Chem Biol Interact http://www.kidney.de/pget.php?&tw=1&pmid=33278462 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33278462 #FOAvip English Wikipedia <ref>{{Cite pmid|33278462}}</ref> 2-Pyridone natural products as inhibitors of SARS-CoV-2 main protease #MMPMID33278462 Forrestall KL; Burley DE; Cash MK; Pottie IR; Darvesh S Chem Biol Interact 2021[Feb]; 335 (ä): 109348 PMID33278462show ga The disease, COVID-19, is caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) for which there is currently no treatment. The SARS-CoV-2 main protease (M(pro)) is an important enzyme for viral replication. Small molecules that inhibit this protease could lead to an effective COVID-19 treatment. The 2-pyridone scaffold was previously identified as a possible key pharmacophore to inhibit SARS-CoV-2 M(pro). A search for natural, antimicrobial products with the 2-pyridone moiety was undertaken herein, and their calculated potency as inhibitors of SARS-CoV-2 M(pro) was investigated. Thirty-three natural products containing the 2-pyridone scaffold were identified from the literature. An in silico methodology using AutoDock was employed to predict the binding energies and inhibition constants (K(i) values) for each 2-pyridone-containing compound with SARS-CoV-2 M(pro). This consisted of molecular optimization of the 2-pyridone compound, docking of the compound with a crystal structure of SARS-CoV-2 M(pro), and evaluation of the predicted interactions and ligand-enzyme conformations. All compounds investigated bound to the active site of SARS-CoV-2 M(pro), close to the catalytic dyad (His-41 and Cys-145). Thirteen molecules had predicted K(i) values <1 muM. Glu-166 formed a key hydrogen bond in the majority of the predicted complexes, while Met-165 had some involvement in the complex binding as a close contact to the ligand. Prominent 2-pyridone compounds were further evaluated for their ADMET properties. This work has identified 2-pyridone natural products with calculated potent inhibitory activity against SARS-CoV-2 M(pro) and with desirable drug-like properties, which may lead to the rapid discovery of a treatment for COVID-19. |Antiviral Agents/chemistry/*metabolism/pharmacokinetics[MESH] |Biological Products/chemistry/*metabolism/pharmacokinetics[MESH] |Caco-2 Cells[MESH] |Catalytic Domain[MESH] |Coronavirus 3C Proteases/chemistry/*metabolism[MESH] |Cysteine Proteinase Inhibitors/chemistry/*metabolism/pharmacokinetics[MESH] |Humans[MESH] |Hydrogen Bonding[MESH] |Molecular Docking Simulation[MESH] |Molecular Structure[MESH] |Protein Binding[MESH] |Pyridones/chemistry/*metabolism/pharmacokinetics[MESH]2-Pyridone natural products as inhibitors of SARS-CoV-2 main protease (epmc).pdf DeepDyve Pubget Overpricing