Lens-epithelium-derived growth-factor (LEDGF/p75)-binding site on HIV-1 integrase (IN), is an attractive target for antiviral chemotherapy. Small-molecule compounds binding to this site are referred as LEDGF-IN inhibitors (LEDGINs). In this study, compound libraries were screened to identify new inhibitors of LEDGF/p75-IN interaction. Ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a reported anti-HIV-1 agent, was identified as a moderate micromolar inhibitor of LEDGF/p75-IN interaction. Ebselen inhibited the interaction by binding to LEDGF/p75 and the ability of ebselen to inhibit the interaction could be reversed by dithiothreitol (DTT). BLI experiment showed that ebselen probably formed selenium-sulphur bonds with reduced thiols in LEDGF/p75. To the best of our knowledge, we showed for the first time that small-molecule compound, ebselen inhibited LEDGF/p75-IN interaction by directly binding to LEDGF/p75. The compound discovered here could be used as probe compounds to design and develop new disrupter of LEDGF/p75-IN interaction.

中文翻译：

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通过靶向LEDGF / p75，含硒药物依布硒仑可有效破坏LEDGF / p75-HIV-1整合酶的相互作用。

HIV-1整合酶（IN）上的晶状体上皮细胞衍生生长因子（LEDGF / p75）结合位点是抗病毒化疗的一个有吸引力的靶标。与该位点结合的小分子化合物称为LE​​DGF-IN抑制剂（LEDGIN）。在这项研究中，筛选化合物文库以鉴定LEDGF / p75-IN相互作用的新抑制剂。Ebselen（2-苯基-1，2-苯并硒基吲哚-3-酮），一种已报道的抗HIV-1药物，被鉴定为LEDGF / p75-IN相互作用的中度微摩尔抑制剂。Ebselen通过与LEDGF / p75结合来抑制相互作用，而ebselen抑制相互作用的能力可以被二硫苏糖醇（DTT）逆转。BLI实验表明依布硒仑可能在LEDGF / p75中形成了硫醇还原的硒硫键。据我们所知，我们首次展示了小分子化合物，依伯硒仑通过直接结合LEDGF / p75抑制LEDGF / p75-IN相互作用。此处发现的化合物可以用作探针化合物，以设计和开发LEDGF / p75-IN相互作用的新型破坏剂。