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10.1016/j.ijbiomac.2021.02.011 http://scihub22266oqcxt.onion/10.1016/j.ijbiomac.2021.02.011 33548321!7859708!33548321     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Int+J+Biol+Macromol 2021 ; 175 (ä): 131-139 Nephropedia Template TP {{tp|p=33548321|t=2021. Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein |pdf=|usr=}}{{33548321}} gab.com Text Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein JO: Int J Biol Macromol http://www.kidney.de/pget.php?&tw=1&pmid=33548321 #FOAvip One of the most crucial characteristic traits of Envelope (E) proteins in the severe acute respiratory syndrome SARS-CoV-1 and NCOVID19 viruses is their membrane-associated oligomerization led ion channel activity, virion assembly, and replication. NMR spectroscopic structural studies of envelope proteins from both the SARS CoV-1/2 reveal that this protein assembles into a homopentamer. Proof of concept studies via truncation mutants on either transmembrane (VFLLV), glycosylation motif (CACCN), hydrophobic helical bundle (PVYVY) as well as replacing C-terminal "DLLV" segments or point mutants such as S68, E69 residues with cysteine have significantly reduced viral titers of SARS-CoV-1. In this present study, we have first developed SARS-2 E protein homology model based on the pentamer coordinates of SARS-CoV-1 E protein (86.4% structural identity) with good stereochemical quality. Next, we focused on the glycosylation motif and hydrophobic helical bundle regions of E protein shown to be important for viral replication. A four feature (4F) model comprising of an acceptor targeting S60 hydroxyl group, a donor feature anchoring the C40 residue, and two hydrophobic features anchoring the V47 L28, L31, Y55, and P51 residues formed the protein based pharmacophore model targeting the glycosylation motif and helical bundle of E protein. Database screening with this 4F protein pharmacophore, ADMET property filtering on enamine small molecule discovery collection yielded a focused library of ~7000 hits. Further molecular docking and visual inspection of docked pose interactions at the above mention V47 L28, L31, Y55, P51, S60, C40 residues led to the identification of 10 best hits. Our STD NMR binding assay results demonstrate that the ligand 3, 2-(2-amino-2-oxo-ethoxy)-N-benzyl-benzamide, binds to NCOVID19 E protein with a binding affinity (K(D)) of 141.7 +/- 13.6 muM. Furthermore, the ligand 3 also showed binding to C-terminal peptide (NR25) as evidenced with the STD spectrums of wild type E protein would serve to confirm the involvement of C-terminal helical bundle as envisaged in this study. Twit Text FOAVip Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein ????Int J Biol Macromol http://www.kidney.de/pget.php?&tw=1&pmid=33548321 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33548321 #FOAvip English Wikipedia <ref>{{Cite pmid|33548321}}</ref> Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein #MMPMID33548321 Mukherjee S; Harikishore A; Bhunia A Int J Biol Macromol 2021[Apr]; 175 (ä): 131-139 PMID33548321show ga One of the most crucial characteristic traits of Envelope (E) proteins in the severe acute respiratory syndrome SARS-CoV-1 and NCOVID19 viruses is their membrane-associated oligomerization led ion channel activity, virion assembly, and replication. NMR spectroscopic structural studies of envelope proteins from both the SARS CoV-1/2 reveal that this protein assembles into a homopentamer. Proof of concept studies via truncation mutants on either transmembrane (VFLLV), glycosylation motif (CACCN), hydrophobic helical bundle (PVYVY) as well as replacing C-terminal "DLLV" segments or point mutants such as S68, E69 residues with cysteine have significantly reduced viral titers of SARS-CoV-1. In this present study, we have first developed SARS-2 E protein homology model based on the pentamer coordinates of SARS-CoV-1 E protein (86.4% structural identity) with good stereochemical quality. Next, we focused on the glycosylation motif and hydrophobic helical bundle regions of E protein shown to be important for viral replication. A four feature (4F) model comprising of an acceptor targeting S60 hydroxyl group, a donor feature anchoring the C40 residue, and two hydrophobic features anchoring the V47 L28, L31, Y55, and P51 residues formed the protein based pharmacophore model targeting the glycosylation motif and helical bundle of E protein. Database screening with this 4F protein pharmacophore, ADMET property filtering on enamine small molecule discovery collection yielded a focused library of ~7000 hits. Further molecular docking and visual inspection of docked pose interactions at the above mention V47 L28, L31, Y55, P51, S60, C40 residues led to the identification of 10 best hits. Our STD NMR binding assay results demonstrate that the ligand 3, 2-(2-amino-2-oxo-ethoxy)-N-benzyl-benzamide, binds to NCOVID19 E protein with a binding affinity (K(D)) of 141.7 +/- 13.6 muM. Furthermore, the ligand 3 also showed binding to C-terminal peptide (NR25) as evidenced with the STD spectrums of wild type E protein would serve to confirm the involvement of C-terminal helical bundle as envisaged in this study. |Amino Acid Sequence[MESH] |Ligands[MESH] |Peptides/metabolism[MESH] |Protein Binding/drug effects[MESH] |SARS-CoV-2/drug effects/*metabolism[MESH] |Small Molecule Libraries/pharmacology[MESH]Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein (epmc).pdf DeepDyve Pubget Overpricing