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

Galatola, Ramona; Vasconcelos, Aimee; Pérez, Yolanda; Cruz, Antonio; Pujol, Montserrat; Alsina, M. A.; Gómara, María J.; Haro, Isabel

doi:10.1016/j.ejmech.2014.09.020

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…Antiviral agents that block the HIV‐1 entry (entry inhibitors) are considered as an effective class of drugs and have been increasingly exploited in recent years . At present, only two members have been clinically approved: Enfuvirtide (T20), a 36‐mer water‐soluble peptide derived from the C‐terminal heptad repeat region of gp41 and Maraviroc (MVC), [7 ] which binds to the CCR5 co‐receptor and inhibits HIV‐1 entry by blocking the gp120‐CCR5 interaction.…”

Section: Introductionmentioning

confidence: 99%

Structural Study of a New HIV‐1 Entry Inhibitor and Interaction with the HIV‐1 Fusion Peptide in Dodecylphosphocholine Micelles

Pérez

Gómara

Yuste

et al. 2017

Chemistry A European J

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Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment.

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Section: Introductionmentioning

confidence: 99%

Structural Study of a New HIV‐1 Entry Inhibitor and Interaction with the HIV‐1 Fusion Peptide in Dodecylphosphocholine Micelles

Pérez

Gómara

Yuste

et al. 2017

Chemistry A European J

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“…The contribution of the vesicles was subtracted from every measurement. The percentage efficiency of the energy transfer was determined from the ratio of the donor in the presence and the absence of the acceptor, at the wavelength of the maximal emission of the donor (λ = 530 nm) 30 .…”

Section: Methodsmentioning

confidence: 99%

Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides

Gómara

Pérez

Martinez

et al. 2019

Sci Rep

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Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139–156) which interacts with the HIV-1 fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target.

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“…At present, it is reported that co-infection of GBV-C (a lymphotropic virus that replicates in primary T and B lymphocytes) with HIV-1 is beneficial to patients with HIV-1 disease [144,145,146], but different views prevail [147]. For safety reasons, the researchers used GBV-C proteins, such as E1 and E2, to study their anti-HIV-1 activity, and they found that some peptides derived from E1 or E2 may inhibit HIV-1 infection by interacting with HIV-1 FP [148,149,150,151,152,153]. The 18-amino acid peptide E1P47 was screened from the E1 protein overlapping peptide library, and it has a broad spectrum of HIV-1 inhibitory activity [154].…”

Section: Protein-and Peptide-based Hiv Entry Inhibitors Targeting mentioning

confidence: 99%

Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41

Wang

et al. 2019

Viruses

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Application of highly active antiretroviral drugs (ARDs) effectively reduces morbidity and mortality in HIV-infected individuals. However, the emergence of multiple drug-resistant strains has led to the increased failure of ARDs, thus calling for the development of anti-HIV drugs with targets or mechanisms of action different from those of the current ARDs. The first peptide-based HIV entry inhibitor, enfuvirtide, was approved by the U.S. FDA in 2003 for treatment of HIV/AIDS patients who have failed to respond to the current ARDs, which has stimulated the development of several series of protein- and peptide-based HIV entry inhibitors in preclinical and clinical studies. In this review, we highlighted the properties and mechanisms of action for those promising protein- and peptide-based HIV entry inhibitors targeting the HIV-1 gp120 or gp41 and discussed their advantages and disadvantages, compared with the current ARDs.

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

Cited by 10 publications

References 46 publications

Structural Study of a New HIV‐1 Entry Inhibitor and Interaction with the HIV‐1 Fusion Peptide in Dodecylphosphocholine Micelles

Structural Study of a New HIV‐1 Entry Inhibitor and Interaction with the HIV‐1 Fusion Peptide in Dodecylphosphocholine Micelles

Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides

Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41

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