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

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 IC50 of 1.04 +/- 0.22 mu M. 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 pepticle, N46, and its mutated version, N46eg, shows synergistic inhibition with an IC50 of 1.39 +/- 0.05 mu M 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. (C) 2008 Elsevier B.V. All rights reserved.