IN-VITRO ANTIMYXOVIRUS AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITIES OF POLYOXOMETALATES
IN-VITRO ANTIMYXOVIRUS AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITIES OF POLYOXOMETALATES
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DOI：
10.1177/095632029500600206
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发表时间：
1995-03-01
影响因子：
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通讯作者：
SCHINAZI, RF
中科院分区：
文献类型：
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作者：
SHIGETA, S;MORI, S;SCHINAZI, RF
多金属氧酸盐已被证明可以抑制逆转录病毒、TOGA病毒、副粘液病毒和疱疹病毒的复制。多金属氧酸盐的抗人类免疫缺陷病毒1型作用的主要机制似乎是抑制病毒与细胞的结合和抑制合胞体的形成。由于粘病毒和艾滋病毒-1通过吸附和穿透病毒以及感染和未感染的细胞与细胞膜相互作用已知，25个多金属氧酸盐在体外检测了抗邻位、抗副粘病毒和抗艾滋病毒-L的活性，在25个化合物中，24个化合物显示出抗流感病毒的活性，11个化合物显示出抗呼吸道合胞病毒的活性，6个化合物显示出抗麻疹病毒的活性。23株被认为在低于产生细胞毒性的浓度下对HIV-1有效。四种具有较强抑制作用的多氧钨酸盐对其他正粘病毒和副粘病毒的抑制作用被证明具有广谱的抗粘病毒活性。HS-058，Keggin三明治化合物K10Fe4(H2O)(2)(PW9O34)(2)。NH(2)O对甲型和乙型流感病毒、呼吸道合胞病毒、麻疹病毒和副流感病毒2有抑制作用，半数有效浓度分别为1、4、21.8、7.4、0.8和0.32 mU/M。HS-058对副流感病毒3型和流行性腮腺炎病毒均无作用，HS-058对马丁达比犬肾(MDCK)和Hep-2细胞的半数细胞毒浓度大于200 mU M，对HMV-2和Vero细胞的半数细胞毒浓度约为50 mU M。在甲型流感和呼吸道合胞病毒感染后的不同时间加入HS-058，可抑制后者与细胞的结合，但对前者无影响，但在较高浓度时，HS-054和HS-058可抑制流感病毒感染的鸡红细胞和呼吸道合胞病毒感染细胞与未感染细胞的合体形成。在病毒吸附前加入四倍于HS-058半数有效浓度的化合物，可完全抑制甲型流感病毒在MDCK细胞中的生长。此外，在病毒吸附后加入HS-058，在低感染复数时对MDCK细胞的病毒产量有抑制作用，而在高复数感染时不抑制病毒产量。
Polyoxometalates have been shown to inhibit the replication of retro-, toga-, paramyxo- and herpesviruses. The primary mechanism of the antihuman immunodeficiency virus type 1 (HIV-1) action of polyoxometalates seems to be inhibition of binding of virus to cells and inhibition of syncytium formation, Since myxoviruses and HIV-1 are known to interact with the cytoplasmic membrane by adsorption and penetration of virus and by fusion of infected and uninfected cells, 25 polyoxometalates were examined for anti-ortho-, anti-paramyxovirus and anti-HIV-l activity in vitro, of the 25 compounds evaluated, 24 showed antiviral effects against influenza virus A, 11 showed activity against respiratory syncytial virus, six showed activity against measles virus, and 23 were considered effective against HIV-1 at a lower concentration than that producing cytotoxicity. Four polyoxotungstates which had potent inhibitory effects were examined for inhibitory effects against additional ortho- and paramyxoviruses, and proved to have a broad spectrum of antimyxoviral activity. HS-058, the Keggin sandwich compound K10Fe4(H2O)(2)(PW9O34)(2) . nH(2)O, was inhibitory against influenza viruses A and B, respiratory syncytial virus, measles virus, and parainfluenza virus 2, with median effective concentrations of 1,4, 21.8, 7.4, 0.8 and 0.32 mu M, respectively. However, HS-058 had no effect on parainfluenza virus 3 or mumps virus, The median cytotoxic concentration of HS-058 for Madin-Darby canine kidney (MDCK) and HEp-2 cells was more than 200 mu M and that for HMV-2 and Vero cells was about 50 mu M. When HS-058 was added at different times after influenza A and respiratory syncytial virus infection, it inhibited binding of the latter but not of the former to cells, However, at higher concentrations, HS-054 and HS-058 inhibited haemolysis of chick erythrocytes by influenza virus and syncytium formation involving respiratory syncytial virus-infected cells and uninfected cells, Four times the median effective antiviral concentration of HS-058 completely inhibited the growth of influenza virus A in MDCK cells when compound was added before virus adsorption. Furthermore, when HS-058 was added after virus adsorption, it inhibited the yield of virus in MDCK cells infected at low but not at high multiplicity of infection.