title: Anti-influenza virus activity of the compound LY253963.
abstract: The compound LY253963 (1,3,4-thiadiazol-2-ylcyanamide) inhibited the in vitro replication of representative influenza A and B viruses in Madin-Darby canine kidney (MDCK) cells at concentrations of 1-3.2 micrograms/ml. The yield of an influenza A (H3N2) virus in primary rhesus monkey kidney (RMK) cells was inhibited at 0.1-0.3 micrograms/ml. However, similar concentrations were inhibitory for the growth of uninfected MCDK or RMK cells. Combination drug studies generally found indifferent interactions between LY253963 and ribavirin or rimantadine. In timing of additional studies, hemagglutinin expression was inhibited to the greatest extent when LY253963 exposure was begun at least 8 h before viral infection, which suggested either slow uptake or intracellular metabolism of LY253963 to an active form. Virus-specific protein synthesis was inhibited to a greater extent by ribavirin 10 micrograms/ml or rimantadine 1 microgram/ml than by LY253963 10 micrograms/ml. No drug-resistant mutants were detected during serial passage of an influenza A (H3N2) virus in the presence of LY253963 1-16 micrograms/ml. In summary, we found that LY253963 inhibited influenza A and B virus replication in several cell types, but that it was associated with cytostatic effects at low concentrations. These studies failed to identify a selective anti-influenza action.
authors.affiliation: Department of Internal Medicine, University of Virginia, School of Medicine, Charlottesville.
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
authors.forename: B S
authors.initials: BS
authors.lastname: Rollins
authors.forename: A J
authors.initials: AJ
authors.lastname: Hay
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D009980:Influenza A virus / Q000187:drug effects / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D013830:Thiadiazoles / Q000494:pharmacology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D009570:Nitriles; D012333:RNA, Messenger; D013830:Thiadiazoles; D014764:Viral Proteins; C067593:1,3,4-thiadiazol-2-ylcyanamide