Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur

Zhenming Jin, Yao Zhao, Yuan Sun, Bing Zhang, Haofeng Wang, Yan Wu, Yan Zhu, Chen Zhu, Tianyu Hu, Xiaoyu Du, Yinkai Duan, Jing Yu, Xiaobao Yang, Xiuna Yang, Kailin Yang, Xiang Liu, Luke W. Guddat, Gengfu Xiao, Leike Zhang, Haitao YangZihe Rao

Research output: Contribution to journalArticlepeer-review

336 Scopus citations

Abstract

The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (Mpro). Here, the X-ray crystal structure of Mpro 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 μM) and is a promising lead compound to develop new antiviral treatment for COVID-19.

Original languageEnglish
Pages (from-to)529-532
Number of pages4
JournalNature Structural and Molecular Biology
Volume27
Issue number6
DOIs
StatePublished - 1 Jun 2020
Externally publishedYes

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