Research Group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Campus Sescelades, Universitat Rovira i Virgili, 43007 Tarragona, Catalonia, Spain.
Int J Mol Sci. 2021 Dec 27;23(1):259. doi: 10.3390/ijms23010259.
In this review, we collected 1765 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M-pro inhibitors from the bibliography and other sources, such as the COVID Moonshot project and the ChEMBL database. This set of inhibitors includes only those compounds whose inhibitory capacity, mainly expressed as the half-maximal inhibitory concentration (IC) value, against M-pro from SARS-CoV-2 has been determined. Several covalent warheads are used to treat covalent and non-covalent inhibitors separately. Chemical space, the variation of the IC inhibitory activity when measured by different methods or laboratories, and the influence of 1,4-dithiothreitol (DTT) are discussed. When available, we have collected the values of inhibition of viral replication measured with a cellular antiviral assay and expressed as half maximal effective concentration (EC) values, and their possible relationship to inhibitory potency against M-pro is analyzed. Finally, the most potent covalent and non-covalent inhibitors that simultaneously inhibit the SARS-CoV-2 M-pro and the virus replication in vitro are discussed.
在这篇综述中，我们从文献和其他来源（如 COVID 登月计划和 ChEMBL 数据库）中收集了 1765 种严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) Mpro 抑制剂。这组抑制剂仅包括那些其抑制能力（主要表示为半最大抑制浓度 (IC) 值）针对 SARS-CoV-2 Mpro 已确定的化合物。几个共价弹头用于分别治疗共价和非共价抑制剂。讨论了化学空间、用不同方法或实验室测量时 IC 抑制活性的变化以及 1,4-二硫苏糖醇 (DTT) 的影响。在有可用数据的情况下，我们还收集了用细胞抗病毒测定法测量的病毒复制抑制的 EC 值，并分析了它们与对 M-pro 的抑制效力之间的可能关系。最后，讨论了同时抑制 SARS-CoV-2 Mpro 和体外病毒复制的最有效共价和非共价抑制剂。
