Development of potent inhibitors of the coxsackievirus 3C protease

Eui Seung Lee, Won Gil Lee, Soo Hyeon Yun, Seong Hwan Rho, Isak Im, Sung Tae Yang, Saravanan Sellamuthu, Yong Jae Lee, Sun Jae Kwon, Ohkmae K. Park, Eun Seok Jeon, Woo Jin Park, Yong Chul Kim

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Abstract

Coxsackievirus B3 (CVB3) 3C protease (3CP) plays essential roles in the viral replication cycle, and therefore, provides an attractive therapeutic target for treatment of human diseases caused by CVB3 infection. CVB3 3CP and human rhinovirus (HRV) 3CP have a high degree of amino acid sequence similarity. Comparative modeling of these two 3CPs revealed one prominent distinction; an Asn residue delineating the S2′ pocket in HRV 3CP is replaced by a Tyr residue in CVB3 3CP. AG7088, a potent inhibitor of HRV 3CP, was modified by substitution of the ethyl group at the P2′ position with various hydrophobic aromatic rings that are predicted to interact preferentially with the Tyr residue in the S2′ pocket of CVB3 3CP. The resulting derivatives showed dramatically increased inhibitory activities against CVB3 3CP. In addition, one of the derivatives effectively inhibited the CVB3 proliferation in vitro.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalBiochemical and biophysical research communications
Volume358
Issue number1
DOIs
Publication statusPublished - 2007 Jun 22

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Keywords

  • 3C protease
  • Coaxsackievirus
  • Inhibitor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, E. S., Lee, W. G., Yun, S. H., Rho, S. H., Im, I., Yang, S. T., Sellamuthu, S., Lee, Y. J., Kwon, S. J., Park, O. K., Jeon, E. S., Park, W. J., & Kim, Y. C. (2007). Development of potent inhibitors of the coxsackievirus 3C protease. Biochemical and biophysical research communications, 358(1), 7-11. https://doi.org/10.1016/j.bbrc.2007.03.208