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Evaluation of metal‐conjugated compounds as inhibitors of 3CL protease of SARS‐CoV
Author(s) -
Hsu John T.-A.,
Kuo Chih-Jung,
Hsieh Hsing-Pang,
Wang Yeau-Ching,
Huang Kuo-Kuei,
Lin Coney P.-C.,
Huang Ping-Fang,
Chen Xin,
Liang Po-Huang
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.015
Subject(s) - protease , chemistry , thimerosal , vero cell , coronavirus , covid-19 , biochemistry , enzyme , medicine , in vitro , disease , pathology , infectious disease (medical specialty) , dermatology
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; M) than using the ion alone ( M).