Direct-acting antivirals and host-targeting strategies to combat enterovirus infections.
Direct-acting antivirals and host-targeting strategies to combat enterovirus infections.
复制标题
DOI：
10.1016/j.coviro.2017.03.009
复制
发表时间：
2017-06
影响因子：
5.9
通讯作者：
van Kuppeveld FJ
中科院分区：
文献类型：
--
作者：
Bauer L;Lyoo H;van der Schaar HM;Strating JR;van Kuppeveld FJ
肠道病毒引起许多人类疾病，但没有抗病毒药物可用。衣壳和病毒酶是有希望的直接作用的抗病毒治疗的目标。基础研究揭示了广谱药物开发的宿主因素。药物再利用筛选已经产生了新的有前途的肠道病毒抑制剂。肠道病毒（例如，脊髓灰质炎病毒、肠病毒-A71、柯萨奇病毒、肠病毒-D68、鼻病毒）包括许多引起各种轻度和更严重疾病的人类病原体，尤其是在幼儿中。不幸的是，治疗肠道病毒感染的抗病毒药物尚未获得批准。在过去的几十年中，已经开发了几种直接作用的抑制剂，包括阻止病毒进入的衣壳结合剂和基因组复制所需的病毒酶的抑制剂。衣壳结合剂和蛋白酶抑制剂已经进行了临床评估，但由于有限的功效或毒性问题而失败。作为一种替代方法，已经鉴定出具有潜在广谱活性的宿主靶向抑制剂。此外，药物再利用筛选最近发现了具有不同病毒和宿主靶点的有希望的新抑制剂。总之，这些发现为开发（广泛的）抗肠道病毒药物带来了希望。
Enteroviruses cause many human diseases, yet no antiviral drugs are available. Capsids and viral enzymes are promising targets for direct-acting antiviral therapy. Fundamental research has unveiled host factors for broad-spectrum drug development. Drug repurposing screens have yielded new promising enterovirus inhibitors. Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.
登录
查看更多内容
影响因子：
16.6
作者：
Desmet, Johan;Verstraete, Kenneth;Bloch, Yehudi;Lorent, Eric;Wen, Yurong;Devreese, Bart;Vandenbroucke, Karen;Loverix, Stefan;Hettmann, Thore;Deroo, Sabrina;Somers, Klaartje;Henderikx, Paula;Lasters, Ignace;Savvides, Savvas N.
通讯作者：
Savvides, Savvas N.
影响因子：
10.5
作者：
Geller, Ron;Vignuzzi, Marco;Frydman, Judith
通讯作者：
Frydman, Judith
影响因子：
4.9
作者：
Hayden, FG;Turner, RB;Zalman, LS
通讯作者：
Zalman, LS
影响因子：
7.6
作者：
Albulescu, Lucian;Bigay, Joelle;Strating, Jeroen R. P. M.
通讯作者：
Strating, Jeroen R. P. M.
影响因子：
5.4
作者：
Asare E;Mugavero J;Jiang P;Wimmer E;Paul AV
通讯作者：
Paul AV