COMPARATIVE INHIBITORY EFFECTS OF VARIOUS NUCLEOSIDE AND NONNUCLEOSIDE ANALOGS ON REPLICATION OF INFLUENZA-VIRUS TYPE-A AND TYPE-B IN-VITRO AND INOVO

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 mug/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 mug/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.