Billard W, Peets E
Antimicrob Agents Chemother. 1974 Jan;5(1):19-24. doi: 10.1128/AAC.5.1.19.
The addition of 5 mM dithiothreitol to a cell-free assay system for influenza ribonucleic acid (RNA) polymerase activity reverses the inhibitory activity otherwise possessed by three established antiviral compounds: selenocystine, 4-(2-propinyloxy)-beta-nitrostyrene, and acetylaranotin. Although 50% or greater enzyme inhibitory activity is repeatedly achieved for these compounds at a concentration of approximately 50 mug/ml (0.1 to 0.25 mM) in the absence of dithiothreitol, no inhibition is seen in its presence at inhibitor concentrations as high as 200 mug/ml. Against the deoxyribonucleic acid-directed RNA polymerases of Escherichia coli and chicken embryo cells, acetylaranotin and 4-(2-propinyloxy)-beta-nitrostyrene caused very little inhibition. Only selenocystine significantly inhibited these two enzymes in the absence of reducing agent, but to an extent substantially less than that obtained against the viral enzyme. These results appear to suggest that influenza RNA polymerase is uniquely sensitive to a variety of structurally diverse antiviral compounds as a consequence of their sulfhydryl reactivity-a fact which might aid in the search for and development of more potent chemotherapeutic agents.
在用于流感核糖核酸（RNA）聚合酶活性的无细胞检测系统中加入5 mM二硫苏糖醇，可逆转三种已确定的抗病毒化合物（即硒代胱氨酸、4-（2-丙炔氧基）-β-硝基苯乙烯和乙酰阿拉诺汀）原本具有的抑制活性。尽管在不存在二硫苏糖醇的情况下，这些化合物在浓度约为50 μg/ml（0.1至0.25 mM）时能反复达到50%或更高的酶抑制活性，但在存在二硫苏糖醇的情况下，即使抑制剂浓度高达200 μg/ml也未见抑制作用。对于大肠杆菌和鸡胚细胞的脱氧核糖核酸指导的RNA聚合酶，乙酰阿拉诺汀和4-（2-丙炔氧基）-β-硝基苯乙烯的抑制作用很小。只有硒代胱氨酸在不存在还原剂的情况下能显著抑制这两种酶，但抑制程度远低于对病毒酶的抑制程度。这些结果似乎表明，流感RNA聚合酶由于其巯基反应性而对多种结构不同的抗病毒化合物具有独特的敏感性——这一事实可能有助于寻找和开发更有效的化疗药物。
