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Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS‐CoV): In search of potent SARS‐CoV entry inhibitors
Author(s) -
Chu LingHon Matthew,
Chan SiuHong,
Tsai SauNa,
Wang Yi,
Cheng Christopher HonKi,
Wong KamBo,
Waye Mary MiuYee,
Ngai SaiMing
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21790
Subject(s) - covid-19 , severe acute respiratory syndrome , coronavirus , virology , betacoronavirus , severe acute respiratory syndrome coronavirus , sars virus , pandemic , medicine , outbreak , infectious disease (medical specialty) , pathology , disease
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. J. Cell. Biochem. 104: 2335–2347, 2008. © 2008 Wiley‐Liss, Inc.