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

Jin Z, Zhao Y, Sun Y, Zhang B, Wang H, Wu Y, Zhu Y, Zhu C, Hu T, Du X, Duan Y, Yu J, Yang X, Yang X, Yang K, Liu X, Guddat LW, Xiao G, Zhang L, Yang H, Rao Z

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??M) and is a promising lead compound to develop new antiviral treatment for COVID-19.

Mesh Terms:
Animals, Betacoronavirus, Chlorocebus aethiops, Coronavirus Infections, Cysteine Endopeptidases, Fluorouracil, Models, Molecular, Pandemics, Pneumonia, Viral, Vero Cells, Viral Nonstructural Proteins

Nat. Struct. Mol. Biol.

Date: Dec. 01, 2019

PubMed ID: 32382072

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Publication Summary

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