A Novel Peptide That Inhibits HIV-1 Entry

The global epidemic of infection by HIV, the cause of AIDS has created an urgent need for novel classes of antiretroviral agent. Besides reverse transcriptase and protease, the viral entry process provides some anti-HIV-1 targets. A new generation of antiviral drugs intended to counter HIV entry into host cells is now under developmentThe CCR5 binding site of gpl20 is also an interesting target for antiHIV-1 drug development, and this binding site can be overlapped by 17b, which is a broadly neutralizing human monoclonal antibody. The hydrophobic and acidic surface of the 17b heavy chain may mimic the tyrosinerich acidic N-tcrminal region of CCR5, which in important for gpl20 binding and HIVl entry, and there is a salt bridge between Arg419 of gp120 and Glu106 of 17b In this study, we have designed a series of peptide mimetics of 17b, based on the co-crystal structure of gp120-CD4-17b. One of these peptides, P20, has been synthesized by the solidphase-pcptide-synthesis method and tested by using two single-cycle HIV-1 that entries into human PBMC, mediated by HIV-1_JR-FL envelope glycoprotein and HIV-1_HXB2 envelope glycoprotein. We have found that this peptide can inhibit R5 HIVl entry effectively, but has no effect on the entry of R4 HIV-1. We concluded that P20 maybe especially bind to R5 HIV-1 envelope glycoprotein (gp120), and inhibits the R5 HIV-1 entry through blocking the interaction between gp120 and co-receptor CCR5.