Peptides derived from HIV-1 gp41 N-terminal heptad repeat(NHR)region(N-peptide)are weak fusion inhibitors due to their tendency to aggregate instead of forming active trimer.We introduced hydrophobic mutations and salt-bridge to stabilize the trimerized N-peptide coiled-coil structure and improve the solubility of the N-peptide.The salt-bridge modified N-peptide LKC142 showed significantly improved inhibitory potency against virus-cell membrane fusion and target binding ability with CHR.Its IC50 was 30 folders lower than the native N-peptide N38MC against T20 sensitive or T20-resistant strains.