Structure-based design and synthesis of highly potent SARS-CoV 3CL protease inhibitors

Yi Ming Shao, Wen Bin Yang, Hung Pin Peng, Min Feng Hsu, Keng Chang Tsai, Tun Hsun Kuo, Andrew H.J. Wang, Po Huang Liang, Chun Hung Lin, An Suei Yang, Chi Huey Wong

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL-3) of the SARS-CoV 3CL protease. A novel C2-symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μM). We believe that this approach has provided a platform for further lead optimization. (Chemical Equation Presented).

Original languageEnglish
Pages (from-to)1654-1657
Number of pages4
JournalChemBioChem
Volume8
Issue number14
DOIs
Publication statusPublished - Sep 24 2007
Externally publishedYes

Keywords

  • Computer modeling
  • Inhibitors
  • Medicinal chemistry
  • Proteases
  • Structure-based design

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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