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Antimicrobial Agents and Chemotherapy, November 2007, p. 3924-3931, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00408-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Novel Small-Molecule Inhibitors of Transmissible Gastroenteritis Virus{triangledown}

Cheng-Wei Yang,1 Yung-Ning Yang,1 Po-Huang Liang,2,{dagger} Chi-Min Chen,3,{dagger} Wei-Liang Chen,1 Hwan-You Chang,4 Yu-Sheng Chao,1 and Shiow-Ju Lee*

Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes,1 Animal Technology Institute Taiwan, Miaoli,3 Institute of Biological Chemistry, Academia Sinica, Taipei,2 Institute of Molecular Medicine, National Tsing Hua University, Hsin Chu, Taiwan, Republic of China4

Received 25 March 2007/ Returned for modification 3 May 2007/ Accepted 14 August 2007

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 (3CLpro) inhibition assay with recombinant 3CLpro and a fluorogenic peptide substrate. A series of benzothiazolium compounds were found to have inhibitory activity against TGEV 3CLpro 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.

* Corresponding author. Mailing address: Division of Biotechnology and Pharmaceutical Research, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China. Phone: 886-37-246166, ext. 35715. Fax: 886-37-586456. E-mail: slee{at}nhri.org.tw

{triangledown} Published ahead of print on 20 August 2007.

{dagger} P.-H.L. and C.-M.C. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, November 2007, p. 3924-3931, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00408-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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