Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA.
Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907 USA.
Bioorg Med Chem Lett. 2023 Nov 15;96:129489. doi: 10.1016/j.bmcl.2023.129489. Epub 2023 Sep 27.
We report here the synthesis and biological evaluation of a series of small molecule SARS-CoV-2 PLpro inhibitors. We compared the activity of selected compounds in both SARS-CoV-1 and SARS-CoV-2 PLpro inhibitory and antiviral assays. We have synthesized and evaluated several new structural variants of previous leads against SARS-CoV-2 PLpro. The replacement of the carboxamide functionality with sulfonamide derivatives resulted in PLpro inhibitors with potent PLpro inhibitory and antiviral activity in VeroE6 cells similar to GRL0617. To obtain molecular insight, we created an optimized model of a potent sulfonamide derivative in the SARS-CoV-2 PLpro active site.
我们在此报告一系列小分子 SARS-CoV-2 PLpro 抑制剂的合成和生物学评估。我们比较了选定化合物在 SARS-CoV-1 和 SARS-CoV-2 PLpro 抑制和抗病毒测定中的活性。我们已经合成并评估了几种针对 SARS-CoV-2 PLpro 的先前先导化合物的新结构变体。用磺酰胺衍生物替代羧酰胺官能团，得到了对 SARS-CoV-2 PLpro 具有强效 PLpro 抑制和抗病毒活性的抑制剂，其活性与 GRL0617 相似。为了获得分子见解，我们在 SARS-CoV-2 PLpro 的活性位点创建了一个优化的强效磺酰胺衍生物模型。
