Definition of an 18-mer Synthetic Peptide Derived from the GB virus C E1 Protein as a New HIV-1 Entry Inhibitor

In this article we report the construction of several peptide libraries scanning the GB virus C (GBV-C) E1 protein and the evaluation of their anti-HIV-1 activity. On the basis of the results, an 18-mer synthetic peptide, specifically the sequence E1(139-156) (namely E1P47), is defined as a new anti-HIV-1 peptide entry inhibitor. The peptide showed similar antiviral activity against viruses from clades A, B, C, D and AE. The broad spectrum of activity against HIV-1 that E1P47 has been demonstrated to have, as well as its capacity to prevent HIV infection by inhibiting (at least partially) viral entry, constitute favourable properties when evaluating this small peptide as a microbicide lead. We consider that these results are of interest for people working in the field of discovering new peptides with the ability of inhibiting HIV and more specifically those involved in studying the relationship of GB virus C and HIV viruses. The results described in the present work indicate the implication of the E1 envelope of the GB virus C in the inhibition of HIV-1. Moreover, our results also highlight the definition of one inhibiting domain within this protein. Thus, taken together the results allow us to consider also the non-pathogenic E1 GB virus C protein as an attractive source of peptides for the development of novel anti-HIV therapies. We strongly believe that the results reported here are important in themselves, so far as we have defined a novel lead compound as in that for the first time the inhibitory role of a highly conserved fragment of the E1 protein is reported.

Group information

The research interests of the Unit of Synthesis and Biomedical Applications of Peptides deal with the use of peptides for the development of new biosensors for the diagnosis of human illnesses and on the selection of therapeutic agents of peptide origin through biophysical testing.

Specifically, in the field of synthetic peptides for the diagnosis and prognosis of rheumatoid arthritis, we aim to identify new antigen peptides, derived from citrullinated/homocitrullinated proteins present in rheumatoid synovial fluid (fibrin, filaggrin, vimentin and enolase) in order to thereby identify those patients who require more aggressive therapies right from the moment of diagnosis of the disease. That would allow greater control of the disease and, consequently, less harm to the articulations and a better prognosis. Moreover, the detection of a single biomarker is not always sufficiently sensitive or precise to discriminate between RA patients with different prognoses, clinical characteristics or responses to therapy. Through the simultaneous analysis of the target peptides, incorporated into a multiplex test, we aim to facilitate the biological fingerprinting of autoantibodies in serum that will be able to identify subgroups of patients with specific clinical characteristics; different prognoses; and who either respond well to, or suffer negative effects from, certain therapeutic interventions. These results could have far-reaching practical implications for establishing the most appropriate therapeutic strategy for RA patients.

Related with the study of peptide human immunodeficiency virus entry inhibitors, we propose the study of new therapeutic agents for the treatment of AIDS, together with the development of a biosensor platform that can be used to detect antibodies against GB virus C in patients co-infected with HIV-1.

Finally, the objective of the research line on peptide controlled-release nanosystems for ocular administration of drugs includes the development of new systems of administration based on liposomes and nanoparticles that are targeted via the use of peptides and that can ensure low levels of irritation, sufficient bioavailability and compatibility with ocular tissues.