Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of the coronavirus disease 2019, for which no effective antiviral therapeutics are available. The SARS-CoV-2 main protease (M^pro) is essential for viral replication and constitutes a promising therapeutic target. Many efforts aimed at deriving effective M^pro inhibitors are currently underway, including an international open-science discovery project, codenamed COVID Moonshot. As part of COVID Moonshot, we used saturation transfer difference nuclear magnetic resonance (STD-NMR) spectroscopy to assess the binding of putative M^pro ligands to the viral protease, including molecules identified by crystallographic fragment screening and novel compounds designed as M^pro inhibitors. In this manner, we aimed to complement enzymatic activity assays of M^pro performed by other groups with information on ligand affinity. We have made the M^pro STD-NMR data publicly available. Here, we provide detailed information on the NMR protocols used and challenges faced, thereby placing these data into context. Our goal is to assist the interpretation of M^pro STD-NMR data, thereby accelerating ongoing drug design efforts.

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是2019年冠状病毒疾病的病因，目前尚无有效的抗病毒治疗方法。SARS-CoV-2主蛋白酶（M ^pro）对于病毒复制是必不可少的，并且构成了有希望的治疗靶标。目前正在进行许多旨在获得有效M ^pro抑制剂的努力，包括代号为COVID Moonshot的国际开放科学发现项目。作为COVID Moonshot的一部分，我们使用饱和转移差异核磁共振（STD-NMR）光谱来评估推定的M ^pro配体与病毒蛋白酶的结合，包括通过晶体学片段筛选鉴定的分子和设计为M的新型化合物^亲抑制剂。通过这种方式，我们旨在补充其他基团对M ^pro的酶活性测定，并提供有关配体亲和力的信息。我们已公开提供M ^pro STD-NMR数据。在这里，我们提供了有关所用NMR协议和面临的挑战的详细信息，从而将这些数据置于上下文中。我们的目标是协助对M ^pro STD-NMR数据的解释，从而加快正在进行的药物设计工作。