Novel recombinant engineered gp 41 N - terminal heptad - repeat trimers : potential as anti - HIV - 1 therapeutics or microbicides

Peptides derived from N-terminal heptad repeat (NHR) of the HIV-1 gp41 are generally poor inhibitors of HIV-1 entry because these peptides tend to aggregate and do not form a trimeric coiled coil. In this study, we have fused portions of gp41 NHR, e.g., N36 or N28, to the T4 fibritin trimerization domain, Foldon (Fd), thus constructing novel NHR-trimers, designated N36Fd or N28Fd, which could be expressed in E. coli cells. The purified N36Fd and N28Fd exhibited SDS-resistant trimeric coiled-coil conformation with improved α-helicity compared to the corresponding N-peptides. They could interact with a C-peptide (e.g., C34) to form stable six-helix bundle and possessed potent anti-HIV-1 activity against a broad spectrum of HIV-1 strains. N28Fd was effective against T20-resistant HIV-1 variants and more resistant to proteinase K compared to T20 (enfuvirtide), a C-peptide-based HIV fusion inhibitor. Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection.