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  • A cyclic GB virus C derived peptide with anti-HIV-1 activity targets the fusion peptide of HIV-1.

A cyclic GB virus C derived peptide with anti-HIV-1 activity targets the fusion peptide of HIV-1.

European journal of medicinal chemistry (2014-09-15)
Ramona Galatola, Aimee Vasconcelos, Yolanda Pérez, Antonio Cruz, Montserrat Pujol, María A Alsina, María J Gómara, Isabel Haro
ABSTRACT

The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22-39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain of the HIV-1 gp41 protein in target cell membranes.

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