title: Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor.
abstract: Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugate to serum albumin. Previous studies demonstrated its in vivo long half-life and potent anti-HIV activity. Here, we focused to characterize its biophysical properties and evaluate its antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to form a stable α-helical conformation with the target sequence and block the fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation. The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B', CRF07_BC and CRF01_AE recombinants that are currently circulating in China. Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20. Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor.
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Chong
authors.forename: Xue
authors.initials: X
authors.lastname: Yao
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Cai
authors.forename: Sheng
authors.initials: S
authors.lastname: Cui
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000821:virology; D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D002460:Cell Line; D055808:Drug Discovery; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D008301:Maleimides / Q000737:chemistry* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D008301:Maleimides; D010446:Peptide Fragments; D010455:Peptides; D000077560:Enfuvirtide; C573334:albuvirtide