An artificial peptide-based HIV-1 fusion inhibitor containing M-T hook structure exhibiting improved antiviral potency and drug resistance profile. (August 2015)

• Record Type: Journal Article
• Authors: Zhu, Xiaojie; Yu, Fei; Liu, Keliang; Lu, Lu; Jiang, Shibo
• Is Part Of: Future virology. Volume 10:Number 8(2015)
• Page Start: 961
• Page End: 969
• Publication Date: 2015-08
• Subjects: artificial peptide -- fusion inhibitor -- gp41 -- HIV-1; Virology -- Periodicals; Virus diseases -- Treatment -- Periodicals; 616.9101
• DOI: 10.2217/fvl.15.56
• Languages: English
• ISSNs: 1746-0794

Abstract

SUMMARY : Aim: We previously designed an artificial HIV-1 fusion inhibitor, PBDtrp-m4HR. Here, we have added two amino acid residues that can form an M-T hook structure at its N-terminus, with the aim of improving its antiviral potency and drug-resistance profile.Methods: Peptides were synthesized and tested for their inhibitory activity on HIV-1 Env-mediated cell–cell fusion and infection by HIV-1 strains, including those resistant to T2635, the third generation HIV fusion inhibitor, as well as its binding affinity to the gp41 NHR-peptide N36.Results: MT-PBDtrp-m4HR exhibited improved inhibitory activity on HIV-1 infection and Env-mediated cell–cell fusion, displayed an improved drug-resistance profile and increased NHR-binding affinity.Conclusion: The added M-T hook is able to enhance or stabilize the interaction between MT-PBDtrp-m4HR and the viral gp41 NHR domain. Therefore, MT-PBDtrp-m4HR has potential to be further developed as a new HIV fusion inhibitor. The approach described in this study can also be used for designing artificial peptides against other enveloped viruses with class I membrane fusion proteins.