title: Comparative inhibitory effects of various nucleoside and nonnucleoside analogues on replication of influenza virus types A and B in vitro and in ovo.
abstract: Six nucleoside analogues, two sulfated polysaccharides, and four protease inhibitors were evaluated in vitro as inhibitors of influenza virus replication. Four guanosine analogues (mizoribine, ribavirin, pyrazofurin, and 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide), the sulfated polysaccharide dextran sulfate (molecular weight 500,000), and two protease inhibitors (camostat mesilate and nafamostat mesilate) were inhibitory to the replication of strains of influenza virus types A and B at concentrations down to 0.3 micrograms/mL. Of these seven compounds, ribavirin, camostat mesilate, and nafamostat mesilate were efficacious in both reducing the virus titer and increasing the survival rate of influenza virus-infected chick embryos. For camostat mesilate, the ED50 (required to improve the survival rate of influenza virus-infected chick embryos by 50%) was 0.80 micrograms/g, and its selectivity index, based on the ratio of the 50% toxic dose (required to reduce the viability of chick embryos by 50%) to ED50, was 280. Camostat mesilate deserves further exploration for its potential in the treatment of influenza virus infection.
authors.affiliation: Department of Microbiology, Fukushima Medical College, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hosoya
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001550:Benzamidines; D002478:Cells, Cultured; D002642:Chick Embryo; D016264:Dextran Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives; D009980:Influenza A virus / Q000187:drug effects* / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects* / Q000254:growth & development; D009705:Nucleosides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012254:Ribavirin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001550:Benzamidines; D004952:Esters; D006146:Guanidines; D009705:Nucleosides; D011480:Protease Inhibitors; C034532:camostat; D006151:Guanosine; D012254:Ribavirin; D016670:Gabexate; D016264:Dextran Sulfate; D000241:Adenosine; C032855:nafamostat