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

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.

HIV-1 inhibiting capacity of novel forms of presentation of GB virus C peptide domains is enhanced by coordination to gold compounds.

Following the report of beneficial effects of co-infection by GB virus C (GBV-C) for HIV-infected patients, we have studied synthetic GBV-C peptides and their relationship with HIV type-1. This paper reports the design and synthesis of new forms of presentation of two peptide inhibitors corresponding to the envelope proteins E1 and E2 of GBV-C, together with a study of their anti-HIV-1 activity. Homogeneous and heterogeneous multiple antigenic peptides (MAPs), lipophilic derivatizations, cyclization and peptide-gold conjugations are the chemical design strategies adopted. Our aim is to enhance the anti-viral potency of the GBV-C peptide domains. Of all the GBV-C peptide derivatives studied, peptide-gold complexes derived from the (22-39) sequence of the GBV-C E1 protein were the most active entry inhibitors. These results support the putative modulation of HIV-1 infection by the GBV-C E1 protein and open new perspectives for the development of novel peptide-derived HIV-1 entry inhibitors.

Effect of synthetic peptides belonging to E2 envelope protein of GB virus C on human immunodeficiency virus type 1 infection.

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.