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[硼-金刚烷衍生物制剂BG-12的抗病毒作用机制]

[The mechanisms of the antiviral action of the bora-adamantane derivative preparation BG-12].

作者信息

Markushin S G, Sinitsyn B V, Ginzburg V P, Khaĭder A M, Klimov A I

出版信息

Vopr Virusol. 1993 May-Jun;38(3):122-6.

PMID:8073750
Abstract

The effect of one of the derivatives of boraadamantane, preparation BG-12, on reproduction of influenza type A and B viruses was studied. This preparation was shown to inhibit multiplication of a wide range of influenza type A and B virus strains. It is important that BG-12 inhibits in cell culture the replication of a mutant of fowl plague virus A/FPV/Weibridge resistant to remantadine. BG-12 was found to exert a marked viricidal effect, to inhibit the hemolytic activity of both influenza A and influenza B viruses, but not the neuraminidase activity of these viruses. The synthesis of some virus-specific proteins was found to be disturbed in influenza B/Ann Arbor/86-infected cells in the presence of BG-12. A FPVBAR mutant of influenza A/FPV/Weibridge (H7N7) virus resistant to BG-12 was obtained. All the BG-12-resistant reassortants inherited genes 4 and 7 coding for hemagglutinin (HA) and membrane proteins (M) from FPVBAR mutant, respectively, and the remaining genes from BG-12-sensitive A/Krasnodar/101/59 (H2N2) virus. The sequencing of a region of the M gene encoding for the transmembrane protein M2 revealed the substitution of Ala30-Thre in this protein. Multiple attempts at generating a mutant of influenza type B virus resistant to BG-12 failed.

摘要

研究了硼金刚烷的一种衍生物制剂BG - 12对甲型和乙型流感病毒复制的影响。结果表明,该制剂能抑制多种甲型和乙型流感病毒株的增殖。重要的是,BG - 12在细胞培养中能抑制对金刚乙胺耐药的禽瘟病毒A/FPV/Weibridge突变株的复制。发现BG - 12具有显著的杀病毒作用,能抑制甲型和乙型流感病毒的溶血活性,但不抑制这些病毒的神经氨酸酶活性。在BG - 12存在的情况下,发现感染乙型流感病毒/安阿伯/86的细胞中一些病毒特异性蛋白的合成受到干扰。获得了对BG - 12耐药的甲型流感病毒A/FPV/Weibridge(H7N7)的FPVBAR突变株。所有对BG - 12耐药的重配体分别从FPVBAR突变株继承了编码血凝素(HA)和膜蛋白(M)的基因4和7,其余基因来自对BG - 12敏感的A/克拉斯诺达尔/101/59(H2N2)病毒。对编码跨膜蛋白M2的M基因区域进行测序,结果显示该蛋白中Ala30被Thre取代。多次尝试构建对BG - 12耐药的乙型流感病毒突变株均未成功。

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