Enfurvitide prevents vertical transmission of multidrug-resistant HIV-1 in pregnancy but does not cross the placenta

Brennan-Benson, Paul; Pakianathan, Mark; Rice, Philip; Bonora, Stefano; Chakraborty, Rana; Hay, Phillip

doi:10.1097/01.aids.0000200535.02232.1b

Cited by 29 publications

(14 citation statements)

References 7 publications

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“…Enfurvitide, a 36-amino acid peptide also known as Fuzeon works by inhibiting the structural rearrangement of HIV-1 gp41 to block the fusion of HIV-1 virions with their target cell membrane. Brennan-Benson et al showed that Fuzeon prevents vertical transmission of HIV-1 in pregnancy, but does not cross the placenta [55]. We have shown that some peptides are effective at preventing HCMV infection.…”

Section: Discussionmentioning

confidence: 56%

Peptide inhibition of human cytomegalovirus infection

Melnik

Garry

Morris

2011

Virol J

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BackgroundHuman cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection.ResultsUsing the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively, and 60% at a concentration of 2.5 μM. While peptides 264-291 and 297-315, individually failed to inhibit viral infection, when combined, they showed 67% inhibition of HCMV infection at a concentration of 0.125 μM each.ConclusionsPeptides designed to target putative fusogenic domains of gB provide a basis for the development of novel therapeutics that prevent HCMV infection.

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Section: Discussionmentioning

confidence: 56%

Peptide inhibition of human cytomegalovirus infection

Melnik

Garry

Morris

2011

Virol J

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“…L'étude de la littérature retrouve, outre nos sept cas, six cas publiés [9][10][11][12]17] et 12 cas présentés [13] (Tableau 2).…”

Section: Discussionunclassified

Utilisation de l’enfuvirtide chez la femme enceinte séropositive VIH, à propos de sept cas

Jeantils

Alloui

Rodrigues

et al. 2009

Gynécologie Obstétrique & Fertilité

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“…Even though several authors describe the use of enfuvirtide in pregnancy, 6,7 cord blood testing has never been reported. Enfuvirtide was not detected in the peripheral blood of two neonates whose mothers had adequate blood levels at delivery.…”

Section: Casementioning

confidence: 99%

Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide

Weizsaecker

Kurowski

Hoffmeister³

et al. 2011

Int J STD AIDS

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The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.

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Enfurvitide prevents vertical transmission of multidrug-resistant HIV-1 in pregnancy but does not cross the placenta

Cited by 29 publications

References 7 publications

Peptide inhibition of human cytomegalovirus infection

Peptide inhibition of human cytomegalovirus infection

Utilisation de l’enfuvirtide chez la femme enceinte séropositive VIH, à propos de sept cas

Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide

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