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

FEBS Lett. 2004 Sep 10;574(1-3):116-20. doi: 10.1016/j.febslet.2004.08.015.


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 microM 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 (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ 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=0.17 microM) than using the ion alone (Ki=1.1 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chlorocebus aethiops
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases
  • Endopeptidases
  • Metals / chemistry*
  • Molecular Sequence Data
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Vero Cells
  • Viral Proteins / antagonists & inhibitors*


  • Metals
  • Protease Inhibitors
  • Viral Proteins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases