Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2

被引：0
|
作者：
Yan, Yong [1 ]
Liu, Hanwen [1 ]
Wu, Di [1 ]
Gu, Zhihao [1 ,2 ,3 ]
Guo, Wenhao [1 ]
Yao, Hequan [1 ]
Lin, Kejiang [1 ]
Li, Xuanyi [1 ]
机构：
[1] China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Nanjing 210009, Peoples R China
[2] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
[3] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
来源：
FUTURE MEDICINAL CHEMISTRY | 2024年 / 16卷 / 09期
基金：
中国国家自然科学基金;
关键词：
3CLpro; 3CLpro inhibitors; molecular docking; SARS-CoV-2; virtual screening based on pharmacophore; MAIN PROTEASE; DISCOVERY;
D O I：
10.4155/fmc-2024-0015
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Background: The epidemic caused by SARS-CoV-2 swept the world in 2019. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in viral replication, and its inhibition could inhibit viral replication. Materials & methods: The virtual screen based on receptor-ligand pharmacophore models and molecular docking were conducted to obtain the novel scaffolds of the 3CLpro. The molecular dynamics simulation was also carried out. All compounds were synthesized and evaluated in biochemical assays. Results: The compound C2 could inhibit 3CLpro with a 72% inhibitory rate at 10 mu M. The covalent docking showed that C2 could form a covalent bond with the Cys145 in 3CLpro. Conclusion: C2 could be a potent lead compound of 3CLpro inhibitors against SARS-CoV-2. [GRAPHICS] .
引用
收藏
页码：887 / 903
页数：17
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