Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.
Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.
复制标题
DOI：
10.1016/j.antiviral.2014.12.003
复制
发表时间：
2015-02
影响因子：
7.6
通讯作者：
McVoy, Michael A.
中科院分区：
文献类型：
--
作者：
Alam, Zohaib;Al-Mandi, Zainab;Zhu, Yali;McKee, Zachary;Parris, Deborah S.;Parikh, Hardik I.;Kellogg, Glen E.;Kuchta, Alison;McVoy, Michael A.
蒽醌 atanyl blue PRL 抑制人巨细胞病毒复制。病毒复制的阻断出现在进入后早期，并大大减少了病毒立即早期基因的表达。在体外，atanyl blue PRL 抑制纯化病毒碱性核酸酶 UL98 的核酸酶活性。 atanyl blue PRL 的抗病毒活性可能通过抑制 UL98 的核酸酶活性来体现。人类巨细胞病毒 (CMV) 会导致免疫功能低下的患者罹患严重疾病，如果在子宫内感染，还会导致严重的出生缺陷。现有的 CMV 抗病毒药物以病毒 DNA 聚合酶为目标，具有显着的毒性，并且存在耐药性。针对不同途径的新药将是有益的。蒽醌大黄素被认为通过阻断病毒核酸酶来抑制单纯疱疹病毒。据报道，大黄素和相关的蒽醌也能抑制 CMV。在本研究中，大黄素降低了 CMV 感染量，EC50 为 4.9 μM，但浓度仅高出两倍时才具有细胞毒性。相关蒽醌酸性蓝 40 和茜素紫 R 仅在高浓度 (238–265 μM) 时抑制 CMV，且具有细胞毒性。然而，atanyl blue PRL 抑制 CMV 的感染量，EC50 为 6.3 μM，显着低于其 50% 细胞毒性浓度 216 μM。 Atanyl blue PRL 可降低 CMV 感染性并抑制传播。当感染后 1 小时添加时，它会显着降低 CMV 立即早期蛋白表达并阻断病毒 DNA 合成。然而，感染后 24 小时添加时，它没有抗病毒活性。有趣的是，atanyl blue PRL 抑制纯化的 CMV UL98 蛋白的核酸酶活性，IC50 分别为 4.5 和 9.3 μM。这些结果表明 atanyl blue PRL 靶向 CMV 复制中非常早期的进入后事件，并表明它可能通过抑制 UL98 发挥作用，使其成为一种新型 CMV 抑制剂。这种化合物可以为感染后最早发生的分子事件提供有价值的见解，并作为抗病毒药物开发的先导结构。
The anthraquinone atanyl blue PRL inhibits human cytomegalovirus replication. The block to viral replication appears early after entry and substantially reduces viral immediate early gene expression. In vitro, atanyl blue PRL inhibits the nuclease activity of purified viral alkaline nuclease, UL98. The antiviral activity of atanyl blue PRL may be manifested through inhibition of UL98’s nuclease activity. Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9 μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1 h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.
登录
查看更多内容
影响因子：
7.6
作者：
Ho TY;Wu SL;Chen JC;Li CC;Hsiang CY
通讯作者：
Hsiang CY
影响因子：
120.7
作者：
Boppana, Suresh B.;Ross, Shannon A.;Fowler, Karen B.
通讯作者：
Fowler, Karen B.
影响因子：
3.7
作者：
Gao, M;Robertson, BJ;Weinheimer, SP
通讯作者：
Weinheimer, SP
影响因子：
7.6
作者：
Bhave, Sukhada;Elford, Howard;McVoy, Michael A.
通讯作者：
McVoy, Michael A.
影响因子：
5.4
作者：
Buerger, I;Reefschlaeger, J;Hallenberger, S
通讯作者：
Hallenberger, S