Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases.
复制标题
DOI：
10.1371/journal.pone.0008350
复制
发表时间：
2009-12-17
期刊：
影响因子：
3.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Hashem AM;Flaman AS;Farnsworth A;Brown EG;Van Domselaar G;He R;Li X
流感病毒会引起严重的感染，可以分别使用疫苗或抗病毒药物来预防或治疗。虽然疫苗是有效的，但它们有许多局限性，并且对现有抗流感药物具有抗药性的流感毒株越来越多地被分离出来。这就需要探索新的抗流感疗法。我们研究了金三羧酸 (ATA)（一种有效的核酸加工酶抑制剂）保护 Madin-Darby 犬肾细胞免受流感感染的潜力。通过中性红测定，我们发现 ATA 具有保护作用，并且通过 RT-PCR 和 ELISA 分别证实 ATA 减少了病毒复制和释放。此外，虽然用 ATA 预处理细胞未能抑制病毒复制，但将病毒与 ATA 预孵育可有效降低病毒滴度，这表明 ATA 可能通过直接与病毒相互作用来引发其抑制作用。电子显微镜显示 ATA 诱导病毒在细胞表面聚集，促使我们确定 ATA 是否可以抑制神经氨酸酶。研究发现 ATA 会损害病毒衍生的重组神经氨酸酶的活性。此外，还发现具有H274Y的奥司他韦耐药H1N1病毒株对ATA敏感。最后，我们观察到当受感染的细胞同时用 ATA 和盐酸金刚烷胺（一种抑制甲型流感病毒 M2 离子通道的抗流感药物）处理时，具有附加保护作用。总的来说，这些数据表明 ATA 通过直接抑制神经氨酸酶而成为一种有效的抗流感药物，并且与盐酸金刚烷胺联合使用时可能成为更有效的抗病毒化合物。
Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.
登录
查看更多内容
影响因子：
7.6
作者：
Hung HC;Tseng CP;Yang JM;Ju YW;Tseng SN;Chen YF;Chao YS;Hsieh HP;Shih SR;Hsu JT
通讯作者：
Hsu JT
影响因子：
5
作者：
Hannoun, C;Megas, F;Piercy, J
通讯作者：
Piercy, J
影响因子：
5.5
作者：
Drape, Robert J.;Macklin, Michael D.;Dean, Hansi J.
通讯作者：
Dean, Hansi J.
影响因子：
4.8
作者：
Haimsohn, M;Beery, R;Geier, A
通讯作者：
Geier, A
影响因子：
4.8
作者：
Beery, R;Haimsohn, M;Geier, A
通讯作者：
Geier, A