Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes
Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes
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DOI：
10.1016/s0166-3542(96)01019-4
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发表时间：
1997-03-01
影响因子：
7.6
通讯作者：
Schinazi, RF
中科院分区：
文献类型：
--
作者：
Barnard, DL;Hill, CL;Schinazi, RF
合成了一系列多金属氧酸盐(POM)，并对其抗呼吸道合胞病毒(RSV)活性进行了评价。对含有各种结构类型的锆、钨、硅、铂、Nb或Ge的POM进行了评估。其中16个化合物对临床分离株Utah 89具有非常显著的抗RSV活性，其半数有效浓度(EC(50))小于或等于3MU M，经病毒细胞病变抑制、中性红摄取和病毒产量降低试验确定了选择性指数>；80。三种方法的EC(50)值具有很好的相关性(皮尔逊相关系数0.90>；)。含钠离子的POM完全失活。含Ge、Nb、Tin和Zirconine的化合物被发现具有很高的效力和选择性。其抗病毒活性不依赖于细胞系。这些化合物对已知的实验室RSV株A2以及其他RSV株也具有相当的活性。为了检测任何病毒株的特异性抑制活性，我们测试了七种POM对其他RSV株的抑制作用；所有POM对人类病毒株的抑制作用几乎相同，表明没有株系特异性。计时研究表明，这些化合物在病毒吸附和穿透过程中抑制作用最强，尽管RSV。当在感染后3小时加入该化合物时，仍然显著抑制；这被认为是很好的日食时期。这些数据表明，这些有效的、无毒的化合物应该作为治疗RSV感染的潜在化疗药物进行进一步研究。(C)1997年爱思唯尔科学公司。
A series of polyoxometalates (POM) were synthesized and evaluated for anti-respiratory syncytial virus (RSV) activity. POM containing zirconium, tungsten, silicon, platinum, niobium or germanium of a variety of structural types have been evaluated. Sixteen of the compounds had very striking anti-RSV activity against a clinical isolate, Utah 89, with median effective concentration (EC(50)) values less than or equal to 3 mu M and selective indices > 80 as determined by viral cytopathic inhibition effect, neutral red uptake and virus yield reduction assays. The EC(50) values for all three assays correlated very well (Pearson correlation coefficients > 0.90>. POM containing sodium cations were totally inactive. Germanium-, niobium-, tin: and zirconium-containing compounds were found to be highly potent and selective. The antiviral activity was not cell line-dependent. The median cytotoxic concentration (IC50) values were generally greater than 100 mu M. The compounds were also comparably active against a known laboratory RSV strain, A2, as well as other RSV strains. To detect any virus strain-specific inhibitory activity, seven POM were tested against other RSV strains; all were nearly equally inhibitory to the human virus strains, suggesting no strain specificity. Timing studies suggested that these compounds were most inhibitory during virus adsorption and penetration, although RSV. was still Significantly inhibited when the compound was added 3 h post-infection; which is considered well into the eclipse period. These data suggest that these potent, non-toxic compounds should be further studied as potential chemotherapeutic agents for treating RSV infections. (C) 1997 Elsevier Science B.V.