Hu Bodan, Chik Kenn Ka-Heng, Chan Jasper Fuk-Woo, Cai Jian-Piao, Cao Hehe, Tsang Jessica Oi-Ling, Zou Zijiao, Hung Yin-Po, Tang Kaiming, Jia Lilong, Luo Cuiting, Yin Feifei, Ye Zi-Wei, Chu Hin, Yeung Man-Lung, Yuan Shuofeng
State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, China.
Pharmaceuticals (Basel). 2022 Aug 27;15(9):1067. doi: 10.3390/ph15091067.
Enterovirus A71 (EV-A71) infection is a major cause of hand, foot, and mouth disease (HFMD), which may be occasionally associated with severe neurological complications. There is currently a lack of treatment options for EV-A71 infection. The Raf-MEK-ERK signaling pathway, in addition to its critical importance in the regulation of cell growth, differentiation, and survival, has been shown to be essential for virus replication. In this study, we investigated the anti-EV-A71 activity of vemurafenib, a clinically approved B-Raf inhibitor used in the treatment of late-stage melanoma. Vemurafenib exhibits potent anti-EV-A71 effect in cytopathic effect inhibition and viral load reduction assays, with half maximal effective concentration (EC) at nanomolar concentrations. Mechanistically, vemurafenib interrupts both EV-A71 genome replication and assembly. These findings expand the list of potential antiviral candidates of anti-EV-A71 therapeutics.
肠道病毒A71（EV-A71）感染是手足口病（HFMD）的主要病因，偶尔可能伴有严重的神经系统并发症。目前针对EV-A71感染缺乏治疗选择。Raf-MEK-ERK信号通路除了在细胞生长、分化和存活的调节中至关重要外，还被证明对病毒复制必不可少。在本研究中，我们研究了维莫非尼（一种临床上批准用于治疗晚期黑色素瘤的B-Raf抑制剂）的抗EV-A71活性。在细胞病变效应抑制和病毒载量降低试验中，维莫非尼表现出强大的抗EV-A71作用，半数最大有效浓度（EC）处于纳摩尔浓度。从机制上讲，维莫非尼会中断EV-A71基因组的复制和组装。这些发现扩展了抗EV-A71治疗潜在抗病毒候选药物的清单。
