Hosoya M, Shigeta S, Ishii T, Suzuki H, De Clercq E
Department of Microbiology, Fukushima Medical College, Japan.
J Infect Dis. 1993 Sep;168(3):641-6. doi: 10.1093/infdis/168.3.641.
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.
对六种核苷类似物、两种硫酸化多糖和四种蛋白酶抑制剂进行了体外评估，以确定它们作为流感病毒复制抑制剂的效果。四种鸟苷类似物（米唑立宾、利巴韦林、吡唑呋喃和5-乙炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺）、硫酸化多糖硫酸葡聚糖（分子量500,000）和两种蛋白酶抑制剂（甲磺酸卡莫司他和甲磺酸萘莫司他）在浓度低至0.3微克/毫升时对甲型和乙型流感病毒株的复制具有抑制作用。在这七种化合物中，利巴韦林、甲磺酸卡莫司他和甲磺酸萘莫司他在降低病毒滴度和提高流感病毒感染鸡胚的存活率方面均有效。对于甲磺酸卡莫司他，使流感病毒感染鸡胚存活率提高50%所需的半数有效剂量（ED50）为0.80微克/克，基于半数毒性剂量（使鸡胚活力降低50%所需剂量）与ED50的比值计算的选择性指数为280。甲磺酸卡莫司他在治疗流感病毒感染方面的潜力值得进一步探索。
