Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV

John T.A. Hsu, Chih Jung Kuo, Hsing Pang Hsieh, Yeau Ching Wang, Kuo Kuei Huang, Coney P.C. Lin, Ping Fang Huang, Xin Chen, Po Huang Liang

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92 Citations (Scopus)


3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 μM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (K i=0.7, 2.4, and 13.7 μM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn 2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17μM) than using the ion alone (Ki=1.1μM).

Original languageEnglish
Pages (from-to)116-120
Number of pages5
JournalFEBS Letters
Issue number1-3
Publication statusPublished - 2004 Sep 10

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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