摘要HIV-1 envelope conformational changes necessary for viral infection make the gp41 subunit a key target for antiviral drugs.Using reverse vaccinology applied to a mucosal HIV-1 neutralizing IgA,we identified P7,a 12 amino-acid peptide at the interface of the N and C-helices of gp41.We now show that P7 interacts with the trimeric HIV-1 envelope cross-clade with a nanomolar affinity,captures gp41 in a 6-Helix Bundle conformation,and binds to infected cells and free virus.Functionally,P7 neutralizes HIV infection cross-clade and inhibits cell-to-cell viral transfer.Adding a lipid tail to P7(Lipo-P7)improved neutralization of primary CD4+T cells by Transmitted/Founder clade B and primary clades A and C viruses.Lipo-P7 also neutralized a T20-resistant virus harboring gp41 G36D,V38M mutations.Altogether,P7 appears as a promising cross-clade HIV-1 antiviral peptide that could also induce protective mucosal IgA levels to prevent sexual HIV infection.