Nsp3 macrodomain of SARS-CoV-2 ; A Target Enabling Package

The conserved macrodomain encoded as non-structural protein 3 (Nsp3 Mac1) is employed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to remove host-derived ribosylation, which is a post-translational modification involved in the production of antiviral cytokines. This TEP provides early tools to develop Nsp3 Mac1 inhibitors, including purification protocols of recombinant proteins, reproducible crystallisation condition suitable for X-ray crystallography fragment screening, biophysical (activity and binding) assays and over 200 fragment hits representing a wide range of chemotypes, that are a starting point for the development of more selective and potent compounds.由非结构蛋白3（Nsp3 Mac1）编码的保守性宏结构域（macrodomain），被严重急性呼吸综合征冠状病毒2（SARS-CoV-2）用于清除宿主来源的核糖基化修饰——该修饰是一种参与抗病毒细胞因子生成的翻译后修饰。本技术实验包（TEP）为Nsp3 Mac1抑制剂的开发提供了早期工具，包括重组蛋白纯化方案、适用于X射线晶体学片段筛选的可重现结晶条件、生物物理（活性与结合）检测方法，以及200余种覆盖多种化学型的片段命中物，可作为开发选择性更强、活性更优的化合物的起始基点。