Departament de Nutrició, Ciències de l'Alimentació I Gastronomía, Institut de Biomedicina (IBUB) and Institut de Química Teórica I Computacional (IQTCUB), Facultat de Farmàcia i Ciències de l'Alimentació, Prat de la Riba 171, 08921, Santa Coloma de Gramenet, Spain.
Instituto de Química Médica (IQM-CSIC), Consejo Superior de Investigaciones Científicas, Juan de la Cierva 6, 28006, Madrid, Spain.
ChemMedChem. 2021 Jan 8;16(1):105-107. doi: 10.1002/cmdc.202000411. Epub 2020 Sep 1.
Here we highlight a sound and unique work reported by Chen and co-workers entitled "HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes" (Xiao et al., Nat. Chem. Biol. 2020, 16, 529). In this article, the authors identify, by means of a clever antibody-guided strategy, several small molecules as fusion inhibitors of HIV-1 replication acting at the membrane proximal external region (MPER) of the HIV-1 envelope (Env) spike. MPER, which was previously recognized as a vaccine target, emerges as a novel druggable target for the discovery of HIV-1 fusion inhibitors. The compounds (exemplified by dequalinium and dequalinium-inspired analogues) prevent the conformational changes of Env from the prefusion species to the intermediate states required for membrane fusion. This work not only paves the way to novel, specific and useful anti-HIV-1 inhibitors, but also discloses new therapeutic strategies against other infectious diseases.
在这里，我们重点介绍了陈及其同事题为“靶向Env 刺突膜近端外部区的 HIV-1 融合抑制剂”的一项出色而独特的工作（Xiao 等人，Nat. Chem. Biol. 2020, 16, 529）。在这篇文章中，作者通过巧妙的抗体导向策略，发现了几种小分子作为 HIV-1 复制的融合抑制剂，这些抑制剂作用于 HIV-1 包膜 (Env) 刺突的膜近端外部区 (MPER)。MPER 先前被认为是疫苗靶点，现在作为发现 HIV-1 融合抑制剂的新的可成药靶点出现。这些化合物（以地喹氯铵和地喹氯铵类似物为例）阻止了 Env 从预融合状态到膜融合所需的中间状态的构象变化。这项工作不仅为新型、特异和有用的抗 HIV-1 抑制剂铺平了道路，也为其他传染病的治疗策略提供了新的思路。
