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Antiviral Res. 2009 Jan;81(1):82-7. doi: 10.1016/j.antiviral.2008.10.001. Epub 2008 Nov 5.

Identification of a minimal peptide derived from heptad repeat (HR) 2 of spike protein of SARS-CoV and combination of HR1-derived peptides as fusion inhibitors.

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Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.


The heptad repeats (HR1 and HR2) of the spike protein of SARS-CoV are highly conserved regions forming a critical 6-helix bundle during the fusion step of virus entry and are attractive targets of entry inhibitors. In this study, we report that a minimal HR2 peptide, P6 of 23-mer, can block the fusion of SARS-CoV with an IC(50) of 1.04+/-0.22 microM. This finding supports the structural prediction of the deep groove of HR1 trimer as a target for fusion inhibitors, and suggests P6 as a potential lead peptide for future drug development. Moreover, combination of an HR-1 peptide, N46, and its mutated version, N46eg, shows synergistic inhibition with an IC(50) of 1.39+/-0.05 microM and combination index of 0.75+/-0.15, suggesting a common strategy to achieve promising inhibition by HR1 peptide for other class I envelope viruses.

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