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10.1021/acs.jmedchem.9b01913 http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.9b01913 32105468!ä!32105468 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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\32105468.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Med+Chem 2020 ; 63 (6): 3131-3141 Nephropedia Template TP {{tp|p=32105468|t=2020. Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design |pdf=|usr=}}{{32105468}} gab.com Text Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=32105468 #FOAvip Structure-based stabilization of protein-protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases. Twit Text FOAVip Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=32105468 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32105468 #FOAvip English Wikipedia <ref>{{Cite pmid|32105468}}</ref> Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design #MMPMID32105468 Lin SM; Lin SC; Hsu JN; Chang CK; Chien CM; Wang YS; Wu HY; Jeng US; Kehn-Hall K; Hou MH J Med Chem 2020[Mar]; 63 (6): 3131-3141 PMID32105468show ga Structure-based stabilization of protein-protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases. |Alkaloids/chemistry/metabolism/*pharmacology[MESH] |Amino Acid Sequence[MESH] |Animals[MESH] |Antiviral Agents/chemistry/metabolism/*pharmacology[MESH] |Chlorocebus aethiops[MESH] |Coronavirus Nucleocapsid Proteins[MESH] |Crystallography, X-Ray[MESH] |Drug Design[MESH] |Hydrophobic and Hydrophilic Interactions[MESH] |Indoles/chemistry/metabolism/*pharmacology[MESH] |Middle East Respiratory Syndrome Coronavirus/chemistry/drug effects[MESH] |Molecular Docking Simulation[MESH] |Nucleocapsid Proteins/chemistry/*metabolism[MESH] |Protein Binding[MESH] |Protein Domains[MESH] |Protein Multimerization/*drug effects[MESH] |Sequence Alignment[MESH]Structure-Based Stabilization of Non-native Protein-Protein Interactio(epmc).pdf DeepDyve Pubget Overpricing