title: Novel small-molecule inhibitors of transmissible gastroenteritis virus.
abstract: 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.
authors: Division of Biotechnology and Pharmaceutical Research, National Health Research Institute, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
authors: Cheng-Wei
authors: CW
authors: Yang
authors: Yung-Ning
authors: YN
authors: Yang
authors: Po-Huang
authors: PH
authors: Liang
authors: Chi-Min
authors: CM
authors: Chen
authors: Wei-Liang
authors: WL
authors: Chen
authors: Hwan-You
authors: HY
authors: Chang
authors: Yu-Sheng
authors: YS
authors: Chao
authors: Shiow-Ju
authors: SJ
authors: Lee
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D052160:Benzothiazoles; D012367:RNA, Viral; D053148:Caspase 3
references: Adv Exp Med Biol. 1993;342:23-8
references: 8209736
references: Can J Vet Res. 1992 Apr;56(2):170-2
references: 1317247
references: Bioorg Med Chem. 2005 Jan 3;13(1):257-64
references: 15582469
references: J Comput Chem. 2005 Apr 15;26(5):484-90
references: 15693056
references: J Virol. 2005 Jun;79(11):7095-103
references: 15890949
references: Dtsch Tierarztl Wochenschr. 2006 Apr;113(4):157-9
references: 16716052
references: Curr Opin Investig Drugs. 2000 Nov;1(3):297-302
references: 11249711
references: J Virol. 2001 Jul;75(14):6402-9
references: 11413307
references: J Gen Virol. 2002 Mar;83(Pt 3):595-9
references: 11842254
references: EMBO J. 2002 Jul 1;21(13):3213-24
references: 12093723
references: Virology. 2002 Oct 25;302(2):321-32
references: 12441076
references: Acta Pharmacol Sin. 2003 Jun;24(6):497-504
references: 12791174
references: Vet Microbiol. 2003 Sep 1;95(3):175-86
references: 12935745
references: J Virol. 2003 Nov;77(22):11952-63
references: 14581532
references: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13190-5
references: 14585926
references: J Biol Chem. 2004 Jan 16;279(3):1637-42
references: 14561748
references: Biochemistry. 2004 May 4;43(17):4906-12
references: 15109248
references: Biochem Biophys Res Commun. 2004 Jun 11;318(4):862-7
references: 15147951
references: Biochem Biophys Res Commun. 2004 Jul 9;319(4):1228-34
references: 15194498
references: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10012-7
references: 15226499
references: Am J Health Syst Pharm. 2004 Jul 1;61(13):1365-74
references: 15287232
references: Curr Opin Drug Discov Devel. 2004 Jul;7(4):446-59
references: 15338954
references: Biochem Biophys Res Commun. 2004 Aug 20;321(2):370-8
references: 15358186
references: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5516-21
references: 10805807
references: J Virol. 2000 Oct;74(19):8793-802
references: 10982321
references: J Virol. 1998 Jun;72(6):4918-24
references: 9573259