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Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): In search of potent SARS-CoV entry inhibitors
Chu, Ling-Hon Matthew ; Chan, Siu-Hong ; Tsai, Sau-Na ; Wang, Yi ; Cheng, Christopher Hon-Ki ; Wong, Kam-Bo ; Waye, Mary Miu-Yee ; Ngai, Sai-Ming
刊名细胞生物化学杂志
2008
关键词SARS-CoV fusion core peptide HEPTAD-REPEAT REGIONS SPIKE PROTEIN COILED-COILS HONG-KONG PEPTIDE GLYCOPROTEIN IDENTIFICATION REPLICATION OUTBREAK DESIGN
DOI10.1002/jcb.21790
英文摘要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.; Biochemistry & Molecular Biology; Cell Biology; SCI(E); 4; ARTICLE; 6; 2335-2347; 104
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/290136]  
专题生命科学学院
推荐引用方式
GB/T 7714
Chu, Ling-Hon Matthew,Chan, Siu-Hong,Tsai, Sau-Na,et al. Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): In search of potent SARS-CoV entry inhibitors[J]. 细胞生物化学杂志,2008.
APA Chu, Ling-Hon Matthew.,Chan, Siu-Hong.,Tsai, Sau-Na.,Wang, Yi.,Cheng, Christopher Hon-Ki.,...&Ngai, Sai-Ming.(2008).Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): In search of potent SARS-CoV entry inhibitors.细胞生物化学杂志.
MLA Chu, Ling-Hon Matthew,et al."Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): In search of potent SARS-CoV entry inhibitors".细胞生物化学杂志 (2008).
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