Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
J Formos Med Assoc. 2010 Feb;109(2):94-105. doi: 10.1016/S0929-6646(10)60029-0.
Human immunodeficiency virus (HIV)-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4) and a coreceptor (CXCR4 or CCR5), followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR) peptide with the N-heptad repeat (NHR) trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.
人类免疫缺陷病毒（HIV）-1 感染是由包膜糖蛋白 gp120 与其细胞受体（CD4）和辅助受体（CXCR4 或 CCR5）结合启动的，随后 gp41 跨膜亚基发生一系列构象变化。这些变化包括融合肽插入靶细胞膜和 C 七肽重复（CHR）肽与 N 七肽重复（NHR）三聚体的结合，形成前发夹融合中间物。然后形成稳定的六螺旋束核心，使病毒包膜和靶细胞膜紧密靠近融合。来自 CHR 区域的肽，如 T20 和 C34，通过与 gp41 融合中间物相互作用来抑制 HIV-1 融合。已经鉴定出许多针对 gp41 NHR-三聚体的抗 HIV-1 肽和小分子化合物。通过结合针对 gp41 融合中间物不同部位的 HIV 融合/进入抑制剂，会产生强大的协同作用，为 HIV 感染/艾滋病带来一种新的潜在治疗策略。在这里，我们概述了抗 HIV 药物的最新发展情况，特别是针对 gp41 融合中间物的药物。
