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10.1002/jcb.21790

http://scihub22266oqcxt.onion/10.1002/jcb.21790
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18442051!7166385!18442051
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suck abstract from ncbi


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pmid18442051      J+Cell+Biochem 2008 ; 104 (6): 2335-47
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  • Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): in search of potent SARS-CoV entry inhibitors #MMPMID18442051
  • Chu LH; Chan SH; Tsai SN; Wang Y; Cheng CH; Wong KB; Waye MM; Ngai SM
  • J Cell Biochem 2008[Aug]; 104 (6): 2335-47 PMID18442051show ga
  • Severe acute respiratory coronavirus (SARS-CoV) spike (S) glycoprotein fusion core consists of a six-helix bundle with the three C-terminal heptad repeat (HR2) helices packed against a central coiled-coil of the other three N-terminal heptad repeat (HR1) helices. Each of the three peripheral HR2 helices shows prominent contacts with the hydrophobic surface of the central HR1 coiled-coil. The concerted protein-protein interactions among the HR helices are responsible for the fusion event that leads to the release of the SARS-CoV nucleocapsid into the target host-cell. In this investigation, we applied recombinant protein and synthetic peptide-based biophysical assays to characterize the biological activities of the HR helices. In a parallel experiment, we employed a HIV-luc/SARS pseudotyped virus entry inhibition assay to screen for potent inhibitory activities on HR peptides derived from the SARS-CoV S protein HR regions and a series of other small-molecule drugs. Three HR peptides and five small-molecule drugs were identified as potential inhibitors. ADS-J1, which has been used to interfere with the fusogenesis of HIV-1 onto CD4+ cells, demonstrated the highest HIV-luc/SARS pseudotyped virus-entry inhibition activity among the other small-molecule drugs. Molecular modeling analysis suggested that ADS-J1 may bind to the deep pocket of the hydrophobic groove on the surface of the central coiled-coil of SARS-CoV S HR protein and prevent the entrance of the SARS-CoV into the host cells.
  • |Amino Acid Sequence[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Computational Biology[MESH]
  • |HIV-1/metabolism[MESH]
  • |Lasers[MESH]
  • |Luciferases/metabolism[MESH]
  • |Models, Molecular[MESH]
  • |Molecular Sequence Data[MESH]
  • |Peptides/chemistry/metabolism[MESH]
  • |Protein Binding[MESH]
  • |Protein Folding[MESH]
  • |Protein Structure, Secondary[MESH]
  • |Recombinant Proteins/chemistry/metabolism[MESH]
  • |Repetitive Sequences, Nucleic Acid[MESH]
  • |Scattering, Radiation[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/*chemistry[MESH]
  • |Thermodynamics[MESH]
  • |Viral Fusion Proteins/*chemistry[MESH]


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