Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur
Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur
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DOI：
10.1038/s41594-020-0440-6
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发表时间：
2020-05-07
影响因子：
16.8
通讯作者：
Rao, Zihe
中科院分区：
文献类型：
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作者：
Jin, Zhenming;Zhao, Yao;Rao, Zihe
SARS-CoV-2与抑制剂卡莫氟的晶体结构揭示了这种化合物的作用机制，并为开发更有效的药物开辟了道路。该药物卡莫氟显示出抑制SARS-CoV-2主要蛋白酶（M-pro）。在这里，与卡莫氟复合的M-pro的X-射线晶体结构显示，卡莫氟的羰基反应基团与催化Cys 145共价结合，而其脂肪酸尾占据疏水S2亚位点。卡莫氟抑制细胞中的病毒复制（EC 50 = 24.30 μ M），是一种有希望开发新的COVID-19抗病毒治疗的先导化合物。
A crystal structure of SARS-CoV-2 with inhibitor carmofur reveals the mechanism of action of this compound and opens the way to develop more potent drugs.The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (M-pro). Here, the X-ray crystal structure of M-pro in complex with carmofur reveals that the carbonyl reactive group of carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 mu M) and is a promising lead compound to develop new antiviral treatment for COVID-19.