期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms232416011
关键词
severe acute respiratory syndrome coronavirus 2; 3CL(pro); anti-coronavirus drug; screening assay; protease
资金
- CAMS Innovation Fund for Medical Sciences [2021-I2M-1-038, 2021-I2M-1-055, 2022-I2M-JB-014]
- National Natural Science Foundation of China [81903679, 81971950]
In this study, Darunavir derivatives that inhibit SARS-CoV-2 3CL(pro) were identified through a high-throughput screening method. These compounds showed favorable antiviral activity and similar potency against Omicron variants.
The effective antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed around the world. The 3C-like protease (3CL(pro)) of SARS-CoV-2 plays a pivotal role in virus replication; it also has become an important therapeutic target for the infection of SARS-CoV-2. In this work, we have identified Darunavir derivatives that inhibit the 3CL(pro) through a high-throughput screening method based on a fluorescence resonance energy transfer (FRET) assay in vitro. We found that the compounds 29# and 50# containing polyphenol and caffeine derivatives as the P2 ligand, respectively, exhibited favorable anti-3CL(pro) potency with EC50 values of 6.3 mu M and 3.5 mu M and were shown to bind to SARS-CoV-2 3CL(pro) in vitro. Moreover, we analyzed the binding mode of the DRV in the 3CL(pro) through molecular docking. Importantly, 29# and 50# exhibited a similar activity against the protease in Omicron variants. The inhibitory effect of compounds 29# and 50# on the SARS-CoV-2 3CL(pro) warrants that they are worth being the template to design functionally improved inhibitors for the treatment of COVID-19.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据