Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2.
Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2.
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Merbromin 是 SARS-CoV-2 3-胰凝乳蛋白酶样蛋白酶的混合型抑制剂
DOI：
10.1016/j.bbrc.2021.12.108
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发表时间：
2022-02-05
影响因子：
3.1
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Chen J;Zhang Y;Zeng D;Zhang B;Ye X;Zeng Z;Zhang XK;Wang Z;Zhou H
3-胰凝乳蛋白酶样蛋白酶（3CLpro）被认为是开发抗SARS-CoV-2药物的有前景的靶点。在此，通过使用酶活性模型的高通量筛选分析了约6000个化合物，并且确定抗菌剂红溴素是3CLpro的有效抑制剂。红汞强烈抑制3CLpro的蛋白水解活性，但不抑制其他三种蛋白酶蛋白酶K、胰蛋白酶和木瓜蛋白酶。Michaelis-Menten动力学分析表明，红溴素对3CLpro的抑制作用为混合型抑制剂，其抑制作用主要表现为增加3CLpro的Km值，降低3CLpro的Kcat值。结合实验和分子对接表明，3CLpro具有两个结合位点。一致地，红溴素显示出与其他三种蛋白酶的弱结合。总之，这些发现表明，红溴素是3CLpro的选择性抑制剂，并提供了一个支架，设计有效的抑制剂SARS-CoV-2。
3-chyomotrypsin like protease (3CLpro) has been considered as a promising target for developing anti-SARS-CoV-2 drugs. Herein, about 6000 compounds were analyzed by high-throughput screening using enzyme activity model, and Merbromin, an antibacterial agent, was identified as a potent inhibitor of 3CLpro. Merbromin strongly inhibited the proteolytic activity of 3CLpro but not the other three proteases Proteinase K, Trypsin and Papain. Michaelis-Menten kinetic analysis showed that Merbromin was a mixed-type inhibitor of 3CLpro, due to its ability of increasing the KM and decreasing the Kcat of 3CLpro. The binding assays and molecular docking suggested that 3CLpro possessed two binding sites for Merbromin. Consistently, Merbromin showed a weak binding to the other three proteases. Together, these findings demonstrated that Merbromin is a selective inhibitor of 3CLpro and provided a scaffold to design effective inhibitors of SARS-CoV-2.
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DOI：
10.1074/jbc.m115.651463
发表时间：
2015-08-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tomar S;Johnston ML;St John SE;Osswald HL;Nyalapatla PR;Paul LN;Ghosh AK;Denison MR;Mesecar AD
通讯作者：
Mesecar AD
影响因子：
5
作者：
Grum-Tokars, Valerie;Ratia, Kiira;Begaye, Adrian;Baker, Susan C.;Mesecar, Andrew D.
通讯作者：
Mesecar, Andrew D.
影响因子：
5.9
作者：
Mody V;Ho J;Wills S;Mawri A;Lawson L;Ebert MCCJC;Fortin GM;Rayalam S;Taval S
通讯作者：
Taval S
影响因子：
64.8
作者：
Hoffmann, Markus;Moesbauer, Kirstin;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
--
作者：
Wright, Christopher;Ross, Carly;Mc Goldrick, Niall
通讯作者：
Mc Goldrick, Niall