Effect of proteins isolated from Brazilian snakes on enterovirus A71 replication cycle: An approach against hand, foot and mouth disease
Effect of proteins isolated from Brazilian snakes on enterovirus A71 replication cycle: An approach against hand, foot and mouth disease
复制标题
DOI：
10.1016/j.ijbiomac.2023.124519
复制
发表时间：
2023-04-25
影响因子：
8.2
通讯作者：
Jardim，Ana Carolina Gomes
中科院分区：
文献类型：
--
作者：
Shimizu，Jacqueline Farinha;Feferbaum-Leite，Shiraz;Jardim，Ana Carolina Gomes
肠道病毒A71（EVA 71）属于小核糖核酸病毒科，是手足口病（HFMD）的主要病原体。目前还没有针对EVA 71的批准的抗病毒药物，因此寻找新的抗EVA 71治疗剂是必要的。在这种情况下，已经报道了从蛇毒中分离的蛋白质对一系列病毒的抗病毒活性。在这里，研究了从Bothropsmoojeni分离的蛋白质CM 10和CM 14以及从Crotalusdurissus terrificus分离的Crotamin和PLA 2CB对EVA 71感染的抗病毒活性。CM 14和Crotamin的选择指数（SI）分别为170.8和120.4，而CM 10和PLA 2CB的SI分别为67.4和12.5。CM14抑制病毒复制的所有步骤（保护作用：76%;杀病毒：99%;和进入后：99%）。类似地，Crotamin抑制高达99%的三个步骤。相反，CM 10和PLA 2CB分别损害EVA 71复制的一个或两个步骤。使用增加的EVA 71滴度进行进一步的剂量反应测定，并且CM 14和克罗他明在高浓度的EVA 71（高达1000 TCID 50）下保留功能性。这些数据表明，从蛇毒中分离的蛋白质是EVA 71的有效抑制剂，可以用作未来开发新型抗病毒药物的支架。
Enterovirus A71 (EVA71) belongs to thePicornaviridaefamily and is the main etiological agent of hand, foot, and mouth disease (HFMD). There is no approved antiviral against EVA71, and therefore the search for novel anti-EVA71 therapeutics is essential. In this context, the antiviral activity of proteins isolated from snake venoms has been reported against a range of viruses. Here, the proteins CM10 and CM14 isolated fromBothropsmoojeni, and Crotamin and PLA2CBisolated fromCrotalusdurissus terrificuswere investigated for their antiviral activity against EVA71 infection. CM14 and Crotamin possessed a selective index (SI) of 170.8 and 120.4, respectively, while CM10 and PLA2CBhad an SI of 67.4 and 12.5, respectively. CM14 inhibited all steps of viral replication (protective effect: 76 %; virucidal: 99 %; and post-entry: 99 %). Similarly, Crotamin inhibited up to 99 % of three steps. In contrast, CM10 and PLA2CBimpaired one or two steps of EVA71 replication, respectively. Further dose-response assays using increasing titres of EVA71 were performed and CM14 and Crotamin retained functionality with high concentrations of EVA71 (up to 1000 TCID50). These data demonstrate that proteins isolated from snake venom are potent inhibitors of EVA71 and could be used as scaffolds for future development of novel antivirals.