BACKGROUND: Enfuvirtide (T-20), a C-terminal heptad repeat (C-HR)-derived peptide of HIV-1 glycoprotein, gp41, effectively suppresses HIV-1 replication through a putative mechanism that involves it acting as a decoy and binding to the N-terminal heptad repeat (N-HR) of the virus. In this study, we address whether the anti-HIV-1 activity of T-20 is antagonized by a variety of N-HR-derived peptides. METHODS: Multinuclear activation of galactosidase indicator assays were used to evaluate T-20 activity in the presence of N-HR-derived peptides. The gp41-derived peptides were chemically synthesized. RESULTS: We demonstrate additive anti-HIV activity when T-20 is used in combination with N-HR-derived peptides that do not have a putative binding region for the tryptophan-rich domain in T-20. The presence of a deep pocket-forming region in the N-HR-derived peptides enhanced their anti-HIV-1 activity, but had little effect on the activity of T-20. CONCLUSIONS: These results indicate that T-20-based antiviral therapies can be combined with N-HR-derived peptides.
BACKGROUND: Enfuvirtide (T-20), a C-terminal heptad repeat (C-HR)-derived peptide of HIV-1 glycoprotein, gp41, effectively suppresses HIV-1 replication through a putative mechanism that involves it acting as a decoy and binding to the N-terminal heptad repeat (N-HR) of the virus. In this study, we address whether the anti-HIV-1 activity of T-20 is antagonized by a variety of N-HR-derived peptides. METHODS: Multinuclear activation of galactosidase indicator assays were used to evaluate T-20 activity in the presence of N-HR-derived peptides. The gp41-derived peptides were chemically synthesized. RESULTS: We demonstrate additive anti-HIV activity when T-20 is used in combination with N-HR-derived peptides that do not have a putative binding region for the tryptophan-rich domain in T-20. The presence of a deep pocket-forming region in the N-HR-derived peptides enhanced their anti-HIV-1 activity, but had little effect on the activity of T-20. CONCLUSIONS: These results indicate that T-20-based antiviral therapies can be combined with N-HR-derived peptides.
Authors: Stefano Aquaro; Roberta D'Arrigo; Valentina Svicher; Giovanni Di Perri; Sergio Lo Caputo; Ubaldo Visco-Comandini; Mario Santoro; Ada Bertoli; Francesco Mazzotta; Stefano Bonora; Valerio Tozzi; Rita Bellagamba; Mauro Zaccarelli; Pasquale Narciso; Andrea Antinori; Carlo Federico Perno Journal: J Antimicrob Chemother Date: 2006-08-05 Impact factor: 5.790
Authors: Chris E Baldwin; Rogier W Sanders; Yiqun Deng; Suzanne Jurriaans; Joep M Lange; Min Lu; Ben Berkhout Journal: J Virol Date: 2004-11 Impact factor: 5.103
Authors: Maria Trott; Svenja Weiβ; Sascha Antoni; Joachim Koch; Hagen von Briesen; Michael Hust; Ursula Dietrich Journal: PLoS One Date: 2014-05-14 Impact factor: 3.240