Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.
Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.
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DOI：
10.1016/j.antiviral.2016.04.003
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发表时间：
2016-07
影响因子：
7.6
通讯作者：
Day, Craig W.
中科院分区：
文献类型：
--
作者：
Smee, Donald F.;Evans, W. Joseph;Nicolaou, K. C.;Tarbet, E. Bart;Day, Craig W.
评价了化合物在横纹肌肉瘤（RD）细胞中针对肠病毒D 68（EV-D 68）的最近2014年临床分离株、EV-68 D的1962株、鼻病毒87（RV-87，血清学上与EV-D 68相同）和肠病毒71（EV-71）的抗病毒活性。供试品包括已知活性的抗小核糖核酸病毒药物（恩伏肟、盐酸胍、吡罗达韦、普考那利和鲁帕韦）、核碱基/核苷类似物（3-脱氮鸟嘌呤和利巴韦林）和三种新型epidithiodiketopiperazines（KCN-2，2 '-epi-19、KCN-19和KCN-21）。其中，鲁帕韦是最有效的，在0.0022-0.0053 μM浓度下，对EV-D 68的病毒致细胞病变效应（EC 50）抑制率为50%，病毒产量抑制率（EC 90）为90%。恩韦肟、普利康那利和KCN化合物在0.01-0.3 μM时显示出有效性; 3-脱氮鸟嘌呤和吡罗达韦在7-13 μM时抑制EV-D 68，盐酸胍和利巴韦林在80-135 μM时抑制。吡罗达韦对EV-71有活性（EC 50为0.78 μM），但对RV-87或EV-D 68无活性，所有其他化合物对EV-71的有效性均低于RV-87和EV-D 68。在低浓度下抑制两种病毒感染的最有希望的化合物是鲁帕韦。在RD细胞中的病毒产量减少（VYR）测定中证实了10种化合物的抗病毒活性，在A549、HeLa-俄亥俄-1和RD细胞中通过细胞病变效应（CPE）测定证实了环肟、盐酸胍和吡罗达韦的抗病毒活性。这些研究可作为进一步临床前发现抗肠道病毒抑制剂的基础。此外，本文观察到的抗病毒特性和生长特征支持EV-D 68应与RV-87一起分类的主张。
Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents (enviroxime, guanidine HCl, pirodavir, pleconaril, and rupintrivir), nucleobase/nucleoside analogs (3-deazaguanine and ribavirin), and three novel epidithiodiketopiperazines (KCN-2,2’-epi-19, KCN-19, and KCN-21). Of these, rupintrivir was the most potent, with 50% inhibition of viral cytopathic effect (EC50) and 90% inhibition (EC90) of virus yield at 0.0022-0.0053 μM against EV-D68. Enviroxime, pleconaril and the KCN compounds showed efficacy at 0.01-0.3 μM; 3-deazaguanine and pirodavir inhibited EV-D68 at 7-13 μM, and guanidine HCl and ribavirin were inhibitory at 80-135 μM. Pirodavir was active against EV-71 (EC50 of 0.78 μM) but not against RV-87 or EV-D68, and all other compounds were less effective against EV-71 than against RV-87 and EV-D68. The most promising compound inhibiting both virus infections at low concentrations was rupintrivir. Antiviral activity was confirmed for the ten compounds in virus yield reduction (VYR) assays in RD cells, and for enviroxime, guanidine HCl, and pirodavir by cytopathic effect (CPE) assays in A549, HeLa-Ohio-1, and RD cells. These studies may serve as a basis for further pre-clinical discovery of anti-enterovirus inhibitors. Furthermore, the antiviral profiles and growth characteristics observed herein support the assertion that EV-D68 should be classified together with RV-87.
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