Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women

Abstract

Microbicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.

Noncovalent PEG Coating of Nanoparticle Drug Carriers Improves the Local Pharmacokinetics of Rectal Anti-HIV Microbicides

“…Antiviral activity of NPs and free EFV was assessed using a Tat-regulated LTR-driven luciferase reporter gene assay in TZM-bl cells as previously described. 17 Briefly, TZM-bl cells (10 4 cells/well) were incubated with serial 10-fold dilutions of NPs or free EFV in medium supplemented with 19.7 μg mL −1 diethylaminoethyl-dextran for 1 h before infection with 400 TCID 50 (half-maximal tissue culture infectious dose) of HIV-1 SG3.1 or 200 TCID 50 HIV-1 NL4-3 isolates. 18 NPs or free EFV were present during incubation with the virus.…”

Antiviral peptides as promising therapeutic drugs

“…Finally, the authors suggest that P3 could be used as an alternative treatment for T-20-resistant HIV-1-infected patients. In a further assay, Bártolo et al [151] formulated P3 in a gel of hydroxyethyl cellulose (HEC) and performed in vivo tests with Balb/c mice. The idea was to create a microbicide that could be used intravaginally to prevent HIV infection.…”

Peptides to combat viral infectious diseases

“…It was suggested that the alpha-helical structure of P3 provides resistance to proteases compared to the unstructured peptides like T-20. Due to the high stability in the human vaginal environment (pH 3.5–4.5) and the ability to retain its bioactivity at 25°, 37°, and 65 °C for a weeklong period, P3 can be a potential candidate for the development of microbicides [ 15 ]. A novel lipopeptide, LP-19 that is derived from the integration of multiple design approaches, targets the conserved pocket region of gp41 and prevents viral fusion to host cells.…”