Novel Small-Molecule Inhibitors of Transmissible Gastroenteritis Virus
Author(s) -
ChengWei Yang,
YungNing Yang,
PoHuang Liang,
ChiMin Chen,
WeiLiang Chen,
HwanYou Chang,
YuSheng Chao,
ShiowJu Lee
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00408-07
Subject(s) - virology , small molecule , virus , biology , microbiology and biotechnology , medicine , genetics
We used swine testicle (ST) cells infected with transmissible gastroenteritis virus (TGEV) and an indirect immunofluorescent assay with antibodies against TGEV spike and nucleocapsid proteins to screen small-molecule compounds that inhibit TGEV replication. Analogues of initial hits were collected and subjected to a 3CL protease (3CL(pro)) inhibition assay with recombinant 3CL(pro) and a fluorogenic peptide substrate. A series of benzothiazolium compounds were found to have inhibitory activity against TGEV 3CL(pro) and to exert anti-TGEV activities in terms of viral protein and RNA replication in TGEV-infected ST cells, with consequent protection of TGEV-infected ST cells from cytopathic effect by blocking the activation of caspase-3.
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