Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;27(6):529-532.
doi: 10.1038/s41594-020-0440-6. Epub 2020 May 7.

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

Zhenming Jin #  1   2 , Yao Zhao #  1 , Yuan Sun #  3 , Bing Zhang  1 , Haofeng Wang  1   4 , Yan Wu  3 , Yan Zhu  1 , Chen Zhu  1 , Tianyu Hu  1 , Xiaoyu Du  1   2 , Yinkai Duan  1 , Jing Yu  1 , Xiaobao Yang  1 , Xiuna Yang  1 , Kailin Yang  5 , Xiang Liu  6 , Luke W Guddat  7 , Gengfu Xiao  3 , Leike Zhang  8 , Haitao Yang  9 , Zihe Rao  1   2   6
Affiliations

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

Zhenming Jin et al. Nat Struct Mol Biol. 2020 Jun.

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.

PubMed Disclaimer

Comment in

  • Structure of SARS-CoV-2 main protease in the apo state.
    Zhou X, Zhong F, Lin C, Hu X, Zhang Y, Xiong B, Yin X, Fu J, He W, Duan J, Fu Y, Zhou H, McCormick PJ, Wang Q, Li J, Zhang J. Zhou X, et al. Sci China Life Sci. 2021 Apr;64(4):656-659. doi: 10.1007/s11427-020-1791-3. Epub 2020 Sep 1. Sci China Life Sci. 2021. PMID: 32880863 Free PMC article. No abstract available.

References

    1. Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). - DOI
    1. Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). - DOI
    1. Hegyi, A. & Ziebuhr, J. Conservation of substrate specificities among coronavirus main proteases. J. Gen. Virol. 83, 595–599 (2002). - DOI
    1. Anand, K. et al. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain. EMBO J. 21, 3213–3224 (2002). - DOI
    1. Yang, H. et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc. Natl Acad. Sci. USA 100, 13190–13195 (2003). - DOI

Publication types

MeSH terms

LinkOut - more resources