A COVID Moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy
A COVID Moonshot: assessment of ligand binding to the SARS-CoV-2 main protease by saturation transfer difference NMR spectroscopy
复制标题
COVID Moonshot：通过饱和转移差核磁共振波谱评估配体与 SARS-CoV-2 主要蛋白酶的结合
DOI：
10.1101/2020.06.17.156679
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kantsadi A
中科院分区：
文献类型：
--
作者：
Kantsadi A
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019年冠状病毒病的病因，目前尚无有效的抗病毒治疗方法。SARS-CoV-2主要蛋白酶（Mpro）是病毒复制所必需的，并且构成了有希望的治疗靶点。目前正在进行许多旨在获得有效Mproinhibitors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分核磁共振（STD-NMR）光谱来评估推定的Mpro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Mpro抑制剂的新型化合物。以这种方式，我们的目的是补充酶活性测定Mproperformed由其他组配体亲和力的信息。我们已经公开了MproSTD-NMR数据。在这里，我们提供了有关所使用的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。我们的目标是帮助解释MproSTD-NMR数据，从而加速正在进行的药物设计工作。
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 (Mpro) is essential for viral replication and constitutes a promising therapeutic target. Many efforts aimed at deriving effective Mproinhibitors 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 Mproligands to the viral protease, including molecules identified by crystallographic fragment screening and novel compounds designed as Mproinhibitors. In this manner, we aimed to complement enzymatic activity assays of Mproperformed by other groups with information on ligand affinity. We have made the MproSTD-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 MproSTD-NMR data, thereby accelerating ongoing drug design efforts.