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10.1016/j.ejmech.2021.113789 http://scihub22266oqcxt.onion/10.1016/j.ejmech.2021.113789 34438124!8372460!34438124     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Eur+J+Med+Chem 2021 ; 225 (ä): 113789 Nephropedia Template TP {{tp|p=34438124|t=2021. Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors |pdf=|usr=}}{{34438124}} gab.com Text Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors JO: Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34438124 #FOAvip SARS-CoV-2 as a positive-sense single-stranded RNA coronavirus caused the global outbreak of COVID-19. The main protease (M(pro)) of the virus as the major enzyme processing viral polyproteins contributed to the replication and transcription of SARS-CoV-2 in host cells, and has been characterized as an attractive target in drug discovery. Herein, a set of 1,4-naphthoquinones with juglone skeleton were prepared and evaluated for the inhibitory efficacy against SARS-CoV-2 M(pro). More than half of the tested naphthoquinones could effectively inhibit the target enzyme with an inhibition rate of more than 90% at the concentration of 10 muM. In the structure-activity relationships (SARs) analysis, the characteristics of substituents and their position on juglone core scaffold were recognized as key ingredients for enzyme inhibitory activity. The most active compound, 2-acetyl-8-methoxy-1,4-naphthoquinone (15), which exhibited much higher potency in enzyme inhibitions than shikonin as the positive control, displayed an IC(50) value of 72.07 +/- 4.84 nM towards M(pro)-mediated hydrolysis of the fluorescently labeled peptide. It fit well into the active site cavity of the enzyme by forming hydrogen bonds with adjacent amino acid residues in molecular docking studies. The results from in vitro antiviral activity evaluation demonstrated that the most potent M(pro) inhibitor could significantly suppress the replication of SARS-CoV-2 in Vero E6 cells within the low micromolar concentrations, with its EC(50) value of about 4.55 muM. It was non-toxic towards the host Vero E6 cells under tested concentrations. The present research work implied that juglone skeleton could be a primary template for the development of potent M(pro) inhibitors. Twit Text FOAVip Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors ????Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34438124 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34438124 #FOAvip English Wikipedia <ref>{{Cite pmid|34438124}}</ref> Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors #MMPMID34438124 Cui J; Jia J Eur J Med Chem 2021[Dec]; 225 (ä): 113789 PMID34438124show ga SARS-CoV-2 as a positive-sense single-stranded RNA coronavirus caused the global outbreak of COVID-19. The main protease (M(pro)) of the virus as the major enzyme processing viral polyproteins contributed to the replication and transcription of SARS-CoV-2 in host cells, and has been characterized as an attractive target in drug discovery. Herein, a set of 1,4-naphthoquinones with juglone skeleton were prepared and evaluated for the inhibitory efficacy against SARS-CoV-2 M(pro). More than half of the tested naphthoquinones could effectively inhibit the target enzyme with an inhibition rate of more than 90% at the concentration of 10 muM. In the structure-activity relationships (SARs) analysis, the characteristics of substituents and their position on juglone core scaffold were recognized as key ingredients for enzyme inhibitory activity. The most active compound, 2-acetyl-8-methoxy-1,4-naphthoquinone (15), which exhibited much higher potency in enzyme inhibitions than shikonin as the positive control, displayed an IC(50) value of 72.07 +/- 4.84 nM towards M(pro)-mediated hydrolysis of the fluorescently labeled peptide. It fit well into the active site cavity of the enzyme by forming hydrogen bonds with adjacent amino acid residues in molecular docking studies. The results from in vitro antiviral activity evaluation demonstrated that the most potent M(pro) inhibitor could significantly suppress the replication of SARS-CoV-2 in Vero E6 cells within the low micromolar concentrations, with its EC(50) value of about 4.55 muM. It was non-toxic towards the host Vero E6 cells under tested concentrations. The present research work implied that juglone skeleton could be a primary template for the development of potent M(pro) inhibitors. |*COVID-19 Drug Treatment[MESH] |Animals[MESH] |Binding Sites[MESH] |COVID-19/pathology/virology[MESH] |Catalytic Domain[MESH] |Cell Survival/drug effects[MESH] |Chlorocebus aethiops[MESH] |Drug Design[MESH] |Drug Evaluation, Preclinical[MESH] |Humans[MESH] |Hydrogen Bonding[MESH] |Molecular Docking Simulation[MESH] |Naphthoquinones/*chemistry/metabolism/pharmacology/therapeutic use[MESH] |Protease Inhibitors/chemistry/metabolism/pharmacology/*therapeutic use[MESH] |SARS-CoV-2/*enzymology/isolation & purification[MESH] |Structure-Activity Relationship[MESH] |Vero Cells[MESH]Discovery of juglone and its derivatives as potent SARS-CoV-2 main pro(epmc).pdf DeepDyve Pubget Overpricing