Synthesis and SARS-CoV-2 3CL Protease Inhibitory Effects of Oxazolidinone Derivatives

The 3-chymotrypsin-like protease (3CLpro) is an attractive target for the development of anti-SARS (severe acute respiratory syndrome) drugs. In this work, a series of oxazolidinone derivatives 3a-3v were synthesized and their inhibitory activities against SARS coronavirus 2 (SARS-CoV-2) 3CLpro were evaluated by the fluorescence resonance energy transfer (FRET)-based enzymatic assay. Among synthesized compounds, 3g displayed the best inhibitory activity, with a half maximal inhibitory concentration (IC50) value of 14.47 μM. Also, docking studies implied that compound 3g was fitted into the active pocket of 3CLpro, forming a hydrogen bond with Glu166.

3-胰凝乳蛋白酶样蛋白酶（3-chymotrypsin-like protease，3CLpro）是抗严重急性呼吸综合征（SARS）药物研发的热门靶点。本研究合成了一系列恶唑烷酮类衍生物3a~3v，并基于荧光共振能量转移（FRET）酶促检测法评估了其对新型冠状病毒（SARS冠状病毒2型，SARS-CoV-2）3CLpro的抑制活性。在所合成的化合物中，3g展现出最优的抑制活性，其半数最大抑制浓度（IC50）值为14.47 μM。此外，分子对接研究表明，化合物3g可嵌入3CLpro的活性口袋，并与Glu166形成氢键。