The nsP3 macrodomain is a conserved protein interaction module that plays essential regula-tory roles in host immune response by recognizing and removing posttranslational ADP-ribosylation sites during SARS-CoV-2 infection. Thus, targeting this protein domain may offer a therapeutic strategy to combat the current and future virus pandemics. To assist in-hibitor development efforts, we report here a comprehensive set of macrodomain crystal structures complexed with diverse naturally-occurring nucleotides, small molecules as well as nucleotide analogues including GS-441524 and its phosphorylated analogue, active me-tabolites of remdesivir. The presented data strengthen our understanding of the SARS-CoV-2 macrodomain structural plasticity and it provides chemical starting points for future inhibi-tor development.

中文翻译：

---

在SARS-CoV-2宏域中对可塑性的结构见解和瑞姆昔韦韦代谢产物GS-441524的结合发现

nsP3宏域是一个保守的蛋白质相互作用模块，通过识别和去除SARS-CoV-2感染期间的翻译后ADP-核糖基化位点，在宿主的免疫反应中发挥重要的调控作用。因此，靶向该蛋白结构域可以提供治疗策略来对抗当前和未来的病毒大流行。为协助抑制剂的开发，我们在此报告了一套完整的宏结构域晶体结构，与各种天然存在的核苷酸，小分子以及包括GS-441524的磷酸化类似物，瑞姆昔韦的活性代谢物等核苷酸类似物复合。提出的数据加深了我们对SARS-CoV-2宏观结构可塑性的理解，并为未来抑制剂的开发提供了化学起点。