化学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
蛋白酶
2019-20冠状病毒爆发
虚拟筛选
2019年冠状病毒病(COVID-19)
组合化学
药物发现
病毒学
酶
生物化学
传染病(医学专业)
医学
疾病
病理
爆发
生物
作者
Xiaodong Dou,Qi Sun,Yameng Liu,Yudong Lu,Caifang Zhang,Gelin Xu,Yifeng Xu,Tongyu Huo,Xin Zhao,Su L,Yunzhe Xing,Luhua Lai,Ning Jiao
标识
DOI:10.1016/j.bmcl.2023.129547
摘要
The COVID-19 caused by SARS-CoV-2 has led to a global pandemic that continues to impact societies and economies worldwide. The main protease (Mpro) plays a crucial role in SARS-CoV-2 replication and is an attractive target for anti-SARS-CoV-2 drug discovery. Herein, we report a series of 3-oxo-1,2,3,4-tetrahydropyrido[1,2-a]pyrazin derivatives as non-peptidomimetic inhibitors targeting SARS-CoV-2 Mpro through structure-based virtual screening and biological evaluation. Further similarity search and structure-activity relationship study led to the identification of compound M56-S2 with the enzymatic IC50 value of 4.0 μM. Moreover, the molecular simulation and predicted ADMET properties, indicated that non-peptidomimetic inhibitor M56-S2 might serve as a useful starting point for the further discovery of highly potent inhibitors targeting SARS-CoV-2 Mpro.
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