NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, #05-01, 28 Medical Drive, Singapore 117456.
Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, Level 3, 18 Science Drive 4, Singapore 117543.
J Antimicrob Chemother. 2017 Nov 1;72(11):2973-2989. doi: 10.1093/jac/dkx224.
Alphaviruses were amongst the first arboviruses to be isolated, characterized and assigned a taxonomic status. They are globally widespread, infecting a large variety of terrestrial animals, birds, insects and even fish. Moreover, they are capable of surviving and circulating in both sylvatic and urban environments, causing considerable human morbidity and mortality. The re-emergence of Chikungunya virus (CHIKV) in almost every part of the world has caused alarm to many health agencies throughout the world. The mosquito vector for this virus, Aedes, is globally distributed in tropical and temperate regions and capable of thriving in both rural and urban landscapes, giving the opportunity for CHIKV to continue expanding into new geographical regions. Despite the importance of alphaviruses as human pathogens, there is currently no targeted antiviral treatment available for alphavirus infection. This mini-review discusses some of the major features in the replication cycle of alphaviruses, highlighting the key viral targets and host components that participate in alphavirus replication and the molecular functions that were used in drug design. Together with describing the importance of these targets, we review the various direct-acting and host-targeting inhibitors, specifically small molecules that have been discovered and developed as potential therapeutics as well as their reported in vitro and in vivo efficacies.
甲病毒是最早被分离、鉴定和分类的虫媒病毒之一。它们在全球广泛分布，感染多种陆地动物、鸟类、昆虫，甚至鱼类。此外，它们能够在森林和城市环境中生存和传播，导致相当多的人类发病率和死亡率。基孔肯雅热病毒（CHIKV）在世界几乎每个地区的再次出现引起了世界各地许多卫生机构的警惕。这种病毒的蚊子媒介——埃及伊蚊，在全球热带和温带地区分布广泛，能够在农村和城市环境中茁壮成长，这使得 CHIKV 有机会继续向新的地理区域扩散。尽管甲病毒是重要的人类病原体，但目前尚无针对甲病毒感染的靶向抗病毒治疗方法。这篇迷你综述讨论了甲病毒复制周期中的一些主要特征，强调了参与甲病毒复制的关键病毒靶标和宿主成分，以及在药物设计中使用的分子功能。在描述这些靶点的重要性的同时，我们还综述了各种直接作用和宿主靶向抑制剂，特别是已被发现和开发为潜在治疗药物的小分子，以及它们在体外和体内的疗效报告。
