Novel small-molecule inhibitors of transmissible gastroenteritis virus.
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.
Yang
Cheng-Wei
CW
Division of Biotechnology and Pharmaceutical Research, National Health Research Institute, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
Yang
Yung-Ning
YN
Liang
Po-Huang
PH
Chen
Chi-Min
CM
Chen
Wei-Liang
WL
Chang
Hwan-You
HY
Chao
Yu-Sheng
YS
Lee
Shiow-Ju
SJ
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D008297:Male; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D052160:Benzothiazoles; D012367:RNA, Viral; D053148:Caspase 3
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