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

Yechun Xu; Hualiang Jiang

doi:10.1007/s13238-020-00769-9

Volume 11 Issue 10

Sep. 2020

Turn off MathJax

Article Contents

Article Navigation > Protein&Cell > 2020 > 11(10): 699-702

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

Citation:

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

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

Citation:

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

PDF( 737 KB)

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

doi: 10.1007/s13238-020-00769-9

Yechun Xu^1,2,
Hualiang Jiang^{1,2,3
,
,}

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

Publish Date: 2020-09-27

Abstract

FullText(HTML)

References(19)

References

[1]	Boschi D, Pippione AC, Sainas S, Lolli ML (2019) Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. Eur J Med Chem 183:111681
[2]	Chi X, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, Zhang Z, Fan P, Dong Y, Yang Y et al (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
[3]	Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Peng J, Liu F et al (2020) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 368:1331-1335
[4]	Diao Y, Lu W, Jin H, Zhu J, Han L, Xu M, Gao R, Shen X, Zhao Z, Liu X et al (2012) Discovery of diverse human dihydroorotate dehydrogenase inhibitors as immunosuppressive agents by structure-based virtual screening. J Med Chem 55:8341-8349
[5]	Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L et al (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368:779-782
[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
[7]	Ji X, Li Z (2020) Medicinal chemistry strategies toward host targeting antiviral agents. Med Res Rev. https://doi.org/10.1002/med.21664
[8]	Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C et al (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582:289-293
[9]	Li S, Luan G, Ren X, Song W, Xu L, Xu M, Zhu J, Dong D, Diao Y, Liu X et al (2015) Rational design of benzylidenehydrazinyl-substituted thiazole derivatives as potent inhibitors of human dihydroorotate dehydrogenase with in vivo anti-arthritic activity. Sci Rep 5:14836
[10]	Loffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA (2005) Pyrimidine pathways in health and disease. Trends Mol Med 11:430-437
[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
[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
[13]	Reis RAG, Calil FA, Feliciano PR, Pinheiro MP, Nonato MC (2017) The dihydroorotate dehydrogenases:past and present. Arch Biochem Biophys 632:175-191
[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
[15]	Xiong R, Zhang L, Li S, Sun Y, Ding M, Wang Y, Zhao Y, Wu Y, Shang W, Jiang X et al (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
[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
[17]	Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M et al (2020) Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 368:1499-1504
[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 alpha-ketoamide inhibitors. Science 368:409-412
[19]	Zhu J, Han L, Diao Y, Ren X, Xu M, Xu L, Li S, Li Q, Dong D, Huang J et al (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