Enterovirus A71 antivirals: Past, present, and future.
Enterovirus A71 antivirals: Past, present, and future.
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DOI：
10.1016/j.apsb.2021.08.017
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发表时间：
2022-04
影响因子：
14.5
通讯作者：
Zheng, Madeleine
中科院分区：
文献类型：
--
作者：
Wang, Jun;Hu, Yanmei;Zheng, Madeleine
关键词：
肠道病毒A71(EV-A71)是一种重要的人类病原体，尤其是在儿童中。EV-A71感染是手足口病(HFMD)的主要原因之一，在严重情况下可导致神经并发症，如急性弛缓性脊髓炎(AFM)。虽然中国有三种EV-A71疫苗可用，但它们没有广泛的保护性，降低了对新出现毒株的效力。目前还没有批准用于EV-A71的抗病毒药物。通过针对病毒蛋白和宿主因子开发针对EV-A71的抗病毒药物已取得重大进展。然而，由于疗效有限或副作用，病毒衣壳抑制剂和蛋白酶抑制剂在人鼻病毒感染的临床试验中失败。这篇综述讨论了EV-A71抗病毒开发的主要发现，分析了每个药物靶点的优势和局限性，并强调了需要解决的知识差距，以推动该领域的发展。EV-A71的复制周期为药物设计提供了多个靶点，最有前景的靶点包括衣壳蛋白、2A和3C酶、2C蛋白和3D聚合酶。
Enterovirus A71 (EV-A71) is a significant human pathogen, especially in children. EV-A71 infection is one of the leading causes of hand, foot, and mouth diseases (HFMD), and can lead to neurological complications such as acute flaccid myelitis (AFM) in severe cases. Although three EV-A71 vaccines are available in China, they are not broadly protective and have reduced efficacy against emerging strains. There is currently no approved antiviral for EV-A71. Significant progress has been made in developing antivirals against EV-A71 by targeting both viral proteins and host factors. However, viral capsid inhibitors and protease inhibitors failed in clinical trials of human rhinovirus infection due to limited efficacy or side effects. This review discusses major discoveries in EV-A71 antiviral development, analyzes the advantages and limitations of each drug target, and highlights the knowledge gaps that need to be addressed to advance the field forward. The EV-A71 replication cycle provides multiple targets for drug design, and the promising ones include the capsid protein, the 2A and 3C proteases, 2C protein, and the 3D polymerase.
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