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Potential treatment of COVID-19 by inhibitors of human dihydroorotate dehydrogenase

  • Yechun Xu 1,2 ,
  • Hualiang Jiang , 1,2,3
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  • 1. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • 2. University of Chinese Academy of Sciences, Beijing 100049, China
  • 3. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

Published date: 15 Oct 2020

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2020 The Author(s)

Cite this article

Yechun Xu , Hualiang Jiang . Potential treatment of COVID-19 by inhibitors of human dihydroorotate dehydrogenase[J]. Protein & Cell, 2020 , 11(10) : 699 -702 . DOI: 10.1007/s13238-020-00769-9

1
Boschi D, Pippione AC, Sainas S, Lolli ML (2019) Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. Eur J Med Chem 183:111681

DOI

2
Chi X, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, Zhang Z, Fan P, Dong Y, Yang Y (2020) A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. https://doi.org/10.1126/science.abc6952

DOI

3
Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Peng J, Liu F (2020) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 368:1331–1335

DOI

4
Diao Y, Lu W, Jin H, Zhu J, Han L, Xu M, Gao R, Shen X, Zhao Z, Liu X (2012) Discovery of diverse human dihydroorotate dehydrogenase inhibitors as immunosuppressive agents by structure-based virtual screening. J Med Chem 55:8341–8349

DOI

5
Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368:779–782

DOI

6
Herrmann ML, Schleyerbach R, Kirschbaum BJ (2000) Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 47:273–289

DOI

7
Ji X, Li Z (2020) Medicinal chemistry strategies toward host targeting antiviral agents. Med Res Rev. https://doi.org/10.1002/med.21664

DOI

8
Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582:289–293

DOI

9
Li S, Luan G, Ren X, Song W, Xu L, Xu M, Zhu J, Dong D, Diao Y, Liu X (2015) Rational design of benzylidenehydrazinylsubstituted thiazole derivatives as potent inhibitors of human dihydroorotate dehydrogenase with in vivo anti-arthritic activity. Sci Rep 5:14836

DOI

10
Loffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA (2005) Pyrimidine pathways in health and disease. Trends Mol Med 11:430–437

DOI

11
Lolli ML, Sainas S, Pippione AC, Giorgis M, Boschi D, Dosio F (2018) Use of human dihydroorotate dehydrogenase (hDHODH) inhibitors in autoimmune diseases and new perspectives in cancer therapy. Recent Pat Anticancer Drug Discov 13:86–105

DOI

12
Madak JT, Bankhead A 3rd, Cuthbertson CR, Showalter HD, Neamati N (2019) Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer. Pharmacol Ther 195:111–131

DOI

13
Reis RAG, Calil FA, Feliciano PR, Pinheiro MP, Nonato MC (2017) The dihydroorotate dehydrogenases: past and present. Arch Biochem Biophys 632:175–191

DOI

14
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30:269–271

DOI

15
Xiong R, Zhang L, Li S, Sun Y, Ding M, Wang Y, Zhao Y, Wu Y, Shang W, Jiang X (2020) Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein Cell. https://doi.org/10.1007/s13238-020-00768-w

DOI

16
Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367:1444–1448

DOI

17
Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M (2020) Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 368:1499–1504

DOI

18
Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R (2020) Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alphaketoamide inhibitors. Science 368:409–412

DOI

19
Zhu J, Han L, Diao Y, Ren X, Xu M, Xu L, Li S, Li Q, Dong D, Huang J (2015) Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase. J Med Chem 58:1123–1139

DOI

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