title: A novel enzyme-linked immunosorbent assay for screening HIV-1 fusion inhibitors targeting HIV-1 Gp41 core structure.
abstract: The gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein mediates the fusion of viral and host cell membranes. As the HIV-1 enters the host cells, the 2 helical regions, HR1 and HR2, in the ectodomain of gp41 can form a 6-helix bundle, which brings the viral and target cell membranes to close proximity and serves as an attractive target for developing HIV-1 fusion inhibitors. Now, there are several cell- and molecule-based assays to identify potential HIV-1 fusion inhibitors targeting gp41. However, these assays cannot be used universally because they are time-consuming, inconvenient, and expensive. In the present study, the authors expressed and purified GST-HR121 and C43-30a proteins that were derived from the HIV-1 gp41 ectodomain region. GST-HR121 has a function similar to the HR1 peptide of gp41, whereas C43-30a is an HR2-derived peptide that added 50 amino acid residues (aa) in the N-terminal of C43. Further research found they could interact with each other, and a potential HIV-1 fusion inhibitor could inhibit this interaction. On the basis of this fact, a novel, rapid, and economic enzyme-linked immunosorbent assay was established, which can be developed for high-throughput screening of HIV-1 fusion inhibitors.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.forename: Yue-Dong
authors.initials: YD
authors.lastname: Gao
authors.forename: Liu-Meng
authors.initials: LM
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Huang
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D015726:Giant Cells / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010455:Peptides; D011993:Recombinant Fusion Proteins