You Qiao, Wu Jing, Lyu Ruining, Cai Yurong, Jiang Na, Liu Ye, Zhang Fang, He Yating, Chen Deyan, Wu Zhiwei
Center for Public Health Research, Medical School of Nanjing University, Nanjing, China.
Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.
BMC Microbiol. 2025 Jan 29;25(1):53. doi: 10.1186/s12866-025-03752-8.
Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), and can cause severe cerebral complications and even fatality in children younger than 5 years old. However, there is no specific medication for EV71 infection in clinical practice. Our previous studies had identified the 6-thioguanine (6-TG), an FDA-approved anticancer drug, as a potential antiviral agent, but its anti-EV71 activity is largely unknown, therefore, we aim to explore the antiviral effect of 6-TG on EV71.
6-TG significantly suppressed EV71 mRNA level, VP1 protein expression, and viral progeny production in HT-29 cells. In EV71-infected HT-29 cells, the 50% cytotoxicity concentration of 6-TG (CC) was > 2000 µM and the 50% inhibitory concentration of 6-TG against EV71 (IC) was 0.9302 µM. Interestingly, the selectivity index (SI) value of 6-TG against EV71 was > 2150.1, which was higher than the SI value (> 66.7) of ribavirin. Mechanistically, 6-TG treatment reduced the expression of baculoviral IAP repeat containing 3 (BIRC3), and further inhibited EV71 replication by attenuating BIRC3-mediated the complete autophagy.
6-TG exerted a significant inhibitory effect on EV71 infection in vitro and prevented EV71-induced the complete autophagy by decreasing BIRC3 expression. Our work provided a basis for the further development of 6-TG as a therapy for EV71-associated HFMD.
肠道病毒71型（EV71）是手足口病（HFMD）的主要病原体之一，可导致5岁以下儿童出现严重的脑部并发症甚至死亡。然而，临床实践中尚无针对EV71感染的特效药物。我们之前的研究已确定6-硫鸟嘌呤（6-TG），一种美国食品药品监督管理局（FDA）批准的抗癌药物，为潜在的抗病毒剂，但其抗EV71活性在很大程度上尚不清楚，因此，我们旨在探索6-TG对EV71的抗病毒作用。
6-TG显著抑制HT-29细胞中EV71的mRNA水平、VP1蛋白表达及病毒子代产生。在感染EV71的HT-29细胞中，6-TG的50%细胞毒性浓度（CC）>2000 μM，6-TG对EV71的50%抑制浓度（IC）为0.9302 μM。有趣的是，6-TG对EV71的选择性指数（SI）值>2150.1，高于利巴韦林的SI值（>66.7）。机制上，6-TG处理降低了含杆状病毒IAP重复序列3（BIRC3）的表达，并通过减弱BIRC3介导的完全自噬进一步抑制EV71复制。
6-TG在体外对EV71感染发挥了显著抑制作用，并通过降低BIRC3表达阻止了EV71诱导的完全自噬。我们的工作为6-TG作为治疗EV71相关手足口病的进一步开发提供了依据。
