Enfuvirtide acetate

Enfuvirtide is a biomimetic peptide inhibitor of HIV-1 fusion with CD4⁺ cells.¹ It inhibits HIV-1 infectivity of HeLa cells stably expressing CD4 by the HXB2 strain (IC₅₀ = 692 pM) and by clinical isolates (IC₉₀s = 6.1-61 nM) in a single-cycle infectivity assay. It also inhibits genomic integration of HIV-1 into human intraepithelial vaginal cells and peripheral blood mononuclear cells (PBMCs; IC₅₀s = 51.2 and 13.58 μM, respectively).² Enfuvirtide binds to a recombinant molecular mimic of HIV-1 glycoprotein gp41 that contains three N-terminal heptad and two C-terminal heptad repeat regions (K_d = 32 nM).³ It also binds to recombinant formyl peptide receptors (FPR) expressed in rat basophilic leukemia cells (IC₅₀ = 5 nM) and attracts and activates human peripheral blood phagocytes, but not T lymphocytes, in vitro when used at a concentration of 100 nM.⁴ Formulations containing enfuvirtide have been used in combination therapy for the treatment of HIV-1/AIDS.

1.Ingallinella, P., Bianchi, E., Ladwa, N.A., et al.Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potencyProc. Natl. Acad. Sci. USA106(14)5801-5806(2009) 2.McElrath, M.J., Ballweber, L., Terker, A., et al.Ex vivo comparison of microbicide efficacies for preventing HIV-1 genomic integration in intraepithelial vaginal cellsAntimicrob. Agents Chemother.54(2)763-772(2010) 3.Champagne, K., Shishido, A., and Root, M.J.Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coilJ. Biol. Chem.284(6)3619-3627(2009) 4.Sun, S.B., Gong, W.H., Gao, J.L., et al.T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptorBlood93(11)3885-3892(1999)