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FEBS Lett. 2004 Sep 10;574(1-3):116-20.

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

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1
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, National Defense Medical Center, Taipei 115, Taiwan, ROC.

Abstract

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).

PMID:
15358550
DOI:
10.1016/j.febslet.2004.08.015
[Indexed for MEDLINE]
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