Shigeta S, Konno K, Yokota T, Nakamura K, De Clercq E
Department of Bacteriology, Fukushima Medical College, Japan.
Antimicrob Agents Chemother. 1988 Jun;32(6):906-11. doi: 10.1128/AAC.32.6.906.
A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited viral cytopathogenicity at concentrations that were lower than those found cytotoxic for the MDCK cells. No differences were observed in the 50% effective doses (based on inhibition of viral cytopathogenicity) of these five compounds for a number of influenza virus type A (subtypes H1N1 and H3N2), B, and C strains. Pyrazofurin showed the lowest 50% effective dose (0.15 microgram/ml), which was about 20- to 30-fold lower than those of the other four compounds. The selectivity indices of the five compounds, calculated as the ratio of the 50% cytotoxic dose (determined by trypan blue exclusion) to the 50% effective dose, were greater than 100. When the selectivity indices were calculated as the ratios of the 50% inhibitory doses for cellular RNA synthesis to the 50% effective doses, they were greater than 100 for ribavirin, pyrazofurin, and 3-deazaguanine but less than 2 for carbodine and cyclopentenyl cytosine. All five compounds inhibited the growth of influenza virus types A and B in MDCK cells at a concentration which was well below their cytotoxicity threshold for MDCK cells and, therefore, deserve further exploration for their potential in the treatment of influenza virus type A, B, and C infections.
检测了一组20种核苷类似物对甲型、乙型和丙型流感病毒株在犬肾传代细胞（MDCK）中的细胞病变效应和生长的抑制作用。在所评估的化合物中，吡唑呋喃、3-脱氮鸟嘌呤、利巴韦林、卡波定和环戊烯基胞嘧啶在低于对MDCK细胞具有细胞毒性的浓度下即可抑制病毒的细胞病变效应。对于多种甲型（H1N1和H3N2亚型）、乙型和丙型流感病毒株，这五种化合物的50%有效剂量（基于对病毒细胞病变效应的抑制）未观察到差异。吡唑呋喃的50%有效剂量最低（0.15微克/毫升），比其他四种化合物低约20至30倍。这五种化合物的选择性指数（计算为50%细胞毒性剂量（通过台盼蓝排斥法测定）与50%有效剂量之比）大于100。当选择性指数计算为细胞RNA合成的50%抑制剂量与50%有效剂量之比时，利巴韦林、吡唑呋喃和3-脱氮鸟嘌呤大于100，而卡波定和环戊烯基胞嘧啶小于2。所有五种化合物均在远低于其对MDCK细胞细胞毒性阈值的浓度下抑制MDCK细胞中甲型和乙型流感病毒的生长，因此，值得进一步探索它们在治疗甲型、乙型和丙型流感病毒感染方面的潜力。
