Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore 636921, Singapore.
Viruses. 2018 Feb 9;10(2):71. doi: 10.3390/v10020071.
Alphaviruses are enveloped, positive single-stranded RNA viruses, typically transmitted by arthropods. They often cause arthralgia or encephalitic diseases in infected humans and there is currently no targeted antiviral treatment available. The re-emergence of alphaviruses in Asia, Europe, and the Americas over the last decade, including chikungunya and o'nyong'nyong viruses, have intensified the search for selective inhibitors. In this review, we highlight key molecular determinants within the alphavirus replication complex that have been identified as viral targets, focusing on their structure and functionality in viral dissemination. We also summarize recent structural data of these viral targets and discuss how these could serve as templates to facilitate structure-based drug design and development of small molecule inhibitors.
甲病毒是有包膜的正单链 RNA 病毒，通常通过节肢动物传播。它们常引起感染人类的关节痛或脑炎疾病，目前尚无针对的抗病毒治疗方法。过去十年中，亚洲、欧洲和美洲的甲病毒再次出现，包括基孔肯雅病毒和奥尼昂昂病毒，这促使人们加紧寻找选择性抑制剂。在这篇综述中，我们重点介绍了在甲病毒复制复合物中已确定为病毒靶点的关键分子决定因素，重点关注它们在病毒传播中的结构和功能。我们还总结了这些病毒靶点的最新结构数据，并讨论了它们如何作为模板促进基于结构的药物设计和小分子抑制剂的开发。
