Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents
Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents
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DOI：
10.1016/s0166-3542(99)00006-6
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发表时间：
1999-04-01
影响因子：
7.6
通讯作者：
Bukrinskaya, AG
中科院分区：
文献类型：
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作者：
Burstein, ME;Serbin, AV;Bukrinskaya, AG
新开发的由化学连接到水溶性聚阴离子基质的金刚烷衍生物组成的抗病毒化合物显示出抑制类淋巴母细胞、HeLa CD 4 + β-半乳糖苷酶（MAGI）细胞和巨噬细胞中的HIV-1感染。化合物的作用通过ELISA测量培养物上清液中的病毒逆转录酶活性和p24以及通过细胞裂解物的免疫印迹来记录。在本文中，我们描述了最有前途的化合物之一，阿曼特获得的数据。Amant在高达1 mg/ml的浓度下对宿主细胞没有毒性。当Amant在感染前或与病毒一起（感染0小时）加入时，观察到MT-4和MAGI细胞中HIV-1复制的抑制，并且即使当在0小时加入的化合物在感染后1.5小时除去时也表达。其对HIV-1和HIV-2复制的抑制浓度（IC_（50））分别为2-6和93 μ g/ml。当在感染后1和2小时加入该化合物时，该化合物的抗HIV-1效果逐渐降低，并且当在感染后4小时加入该化合物时没有观察到抑制，这表明该化合物作为亲膜性药物阻断复制的早期步骤。它完全阻止Gag蛋白转运到细胞核中。用Amant预处理病毒并不降低其感染活性。经典的金刚烷衍生物金刚烷胺和金刚乙胺盐酸盐不抑制HIV复制。(C)1999 Elsevier Science B. V.保留所有权利。
Newly developed antiviral compounds consisting of an adamantane derivative chemically linked to a water-soluble polyanionic matrix were shown to inhibit HIV-1 infection in lymphoblastoid cells, HeLa CD4 + beta-galactosidase (MAGI) cells and macrophages. The effect of the compounds was recorded by measuring viral reverse transcriptase activity and p24 by ELISA in culture supernatant and by immunoblotting of cell lysates. In this paper we describe the data obtained with one of the most promising compounds, Amant. Amant was not toxic for the host cells at concentrations as high as 1 mg/ml. The inhibition of HIV-1 replication in MT-4 and MAGI cells was observed when Amant was added either before infection or with the virus (0 h of infection), and was expressed even when the compound added at 0 h was removed 1.5 h after infection. Its inhibitory concentration (IC50) against HIV-1 and HIV-2 replication was 2-6 and 93 mu g/ml, respectively. The anti-HIV-1 effect of the compound was gradually decreased when it was added 1 and 2 h post infection, and no inhibition was observed when the compound was added 4 h after infection, suggesting that the compound as a membranotropic drug blocks an early step of replication. It completely prevented the transport of Gag proteins into the nuclei. Pretreatment of the virus with Amant did not reduce its infectious activity. The classical adamantane derivatives amantadine and rimantadine hydrochloride did not inhibit HIV replication. (C) 1999 Elsevier Science B.V. All rights reserved.