Novel small-molecule inhibitors of transmissible gastroenteritis virus

Antimicrob Agents Chemother. 2007 Nov;51(11):3924-31. doi: 10.1128/AAC.00408-07. Epub 2007 Aug 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacology
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique, Indirect / methods
  • Male
  • Microbial Sensitivity Tests
  • Molecular Structure
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Transmissible gastroenteritis virus / drug effects*
  • Transmissible gastroenteritis virus / genetics
  • Transmissible gastroenteritis virus / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Benzothiazoles
  • RNA, Viral
  • Caspase 3