Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors.
Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors.
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DOI：
10.1038/s41467-021-22362-2
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发表时间：
2021-04-01
影响因子：
16.6
通讯作者：
Ho DD
中科院分区：
文献类型：
--
作者：
Iketani S;Forouhar F;Liu H;Hong SJ;Lin FY;Nair MS;Zask A;Huang Y;Xing L;Stockwell BR;Chavez A;Ho DD
我们报告了三种结构不同的化合物-化合物4，GC 376和MAC-5576 -作为SARS-CoV-2 3CL蛋白酶抑制剂的鉴定。这些化合物与蛋白酶复合的结构揭示了进一步开发的策略，以及设计SARS-CoV-2 3CL蛋白酶抑制剂的一般原则。因此，这些化合物可以作为先导化合物，为构建有效的SARS-CoV-2 3CL蛋白酶抑制剂奠定基础。重要的SARS-CoV-2 3CL蛋白酶作为药物靶点是令人感兴趣的。在这里，作者鉴定了三种3CL抑制剂，并在体外和基于细胞的测定中对它们进行了表征，并且他们还提出了与受体结合的3CL晶体结构，这可能允许设计改进的化合物。
We report the identification of three structurally diverse compounds – compound 4, GC376, and MAC-5576 – as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors. The essential SARS-CoV-2 3CL protease is of interest as a drug target. Here, the authors identify three 3CL inhibitors and characterize them both in vitro and with a cell-based assay, and they also present the inhibitor-bound 3CL crystal structures, which may allow for the design of improved compounds.