Kirsi J J, McKernan P A, Burns N J, North J A, Murray B K, Robins R K
Antimicrob Agents Chemother. 1984 Oct;26(4):466-75. doi: 10.1128/AAC.26.4.466.
The antiviral effects of selenazofurin (2-beta-D-ribofuranosylselenazole-4-carboxamide, selenazole), ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), and 3-deazaguanosine (6-amino-1-beta-D-ribofuranosylimidazo-[4.5-C]pyridin-4(5H)-one) were investigated separately and in various combinations in an in vitro study. The combination interactions were evaluated at seven drug concentrations, graphically (isobolograms) or by using fractional inhibitory concentration indices against mumps, measles, parainfluenza virus type 3, vaccinia and herpes simplex virus type 2 viruses in Vero and HeLa cells. Selenazofurin in combination with ribavirin produced the greatest synergistic antiviral activity. However, the degree of synergy depended on the virus and cell line used. In contrast, selenazofurin combined with 3-deazaguanosine consistently yielded an indifferent or an antagonistic response, or both, whereas the ribavirin-3-deazaguanosine interaction was additive against the same viruses. Single-drug cytotoxicity was minimal for the cytostatic agents selenazofurin and ribavirin but was markedly higher for cytocidal 3-deazaguanosine, as determined by relative plating efficiency after drug exposure. The drug combinations did not significantly increase cytotoxicity (they were only additive) when used on uninfected cells. Therefore, the enhanced antiviral activities of the drug combinations (shown to be synergistic) were due to specific effects against viral replication. These results indicated that in Vero and HeLa cells (i) the combination of selenazofurin and ribavirin produced an enhanced antiviral effect, thus requiring smaller amounts of drug to cause the same antiviral effect relative to a single compound; (ii) selenazofurin when compared with ribavirin and 3-deazaguanosine appeared to have a somewhat different mode of antiviral action; (iii) 3-deazaguanosine combined with selenazofurin was an unsuitable antiviral combination; and (iv) the antiviral activity of 3-deazaguanosine appeared to be due largely to its general overall cytotoxic effect.
在一项体外研究中，分别研究了硒唑嘌呤（2-β-D-呋喃核糖基硒唑-4-甲酰胺，硒唑）、利巴韦林（1-β-D-呋喃核糖基-1,2,4-三唑-3-甲酰胺）和3-去氮鸟苷（6-氨基-1-β-D-呋喃核糖基咪唑并-[4.5-C]吡啶-4(5H)-酮）的抗病毒作用以及各种组合的抗病毒作用。在七种药物浓度下，通过图形（等效线图）或使用分数抑制浓度指数，评估了针对腮腺炎病毒、麻疹病毒、3型副流感病毒、痘苗病毒和2型单纯疱疹病毒在Vero细胞和HeLa细胞中的联合相互作用。硒唑嘌呤与利巴韦林联合产生了最大的协同抗病毒活性。然而，协同程度取决于所使用的病毒和细胞系。相比之下，硒唑嘌呤与3-去氮鸟苷联合始终产生无作用或拮抗反应，或两者兼有，而利巴韦林与3-去氮鸟苷的相互作用对相同病毒是相加性的。对于细胞生长抑制剂硒唑嘌呤和利巴韦林，单药细胞毒性最小，但对于具有细胞杀伤作用的3-去氮鸟苷，细胞毒性明显更高，这是通过药物暴露后的相对接种效率确定的。当用于未感染细胞时，药物组合并未显著增加细胞毒性（它们只是相加性的）。因此，药物组合增强的抗病毒活性（显示为协同作用）是由于对病毒复制的特异性作用。这些结果表明，在Vero细胞和HeLa细胞中：（i）硒唑嘌呤和利巴韦林的组合产生了增强的抗病毒效果，因此相对于单一化合物，产生相同抗病毒效果所需的药物量更少；（ii）与利巴韦林和3-去氮鸟苷相比，硒唑嘌呤似乎具有 somewhat不同的抗病毒作用模式；（iii）3-去氮鸟苷与硒唑嘌呤联合是不合适的抗病毒组合；（iv）3-去氮鸟苷的抗病毒活性似乎主要归因于其总体细胞毒性作用。
