Chen Yongkang, Li Xiaohong, Wang Min, Li Yuan, Fan Jun, Yan Jingjing, Zhang Shuye, Lu Lu, Zou Peng
Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Clinical Center for BioTherapy and Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Curr Res Microb Sci. 2023 Sep 16;5:100203. doi: 10.1016/j.crmicr.2023.100203. eCollection 2023.
Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.
感染柯萨奇病毒A10（CV - A10）可引发手足口病，还与包括病毒性肺炎、无菌性和病毒性脑膜炎在内的严重并发症相关。柯萨奇病毒感染在急性心肌梗死的发病机制以及成人1型糖尿病风险增加方面可能也起作用。然而，目前尚无获批的疫苗或直接抗病毒药物可用于预防或治疗柯萨奇病毒感染。在此，我们报告GC376能有效抑制不同细胞系中的CV - A10感染且无细胞毒性，显著抑制病毒蛋白的产生，并大幅降低感染性子代病毒颗粒的产量。进一步研究表明，作为病毒3C蛋白酶抑制剂的GC376有可能抑制病毒多聚蛋白切割成单个功能蛋白，从而抑制CV - A10的复制。此外，该药物对包括CV - A6、CV - A7和CV - A16在内的多种血清型柯萨奇病毒均表现出抗病毒活性，这表明GC376是一种广谱抗柯萨奇病毒抑制剂，且3C蛋白酶是开发抗柯萨奇病毒药物的一个有前景的靶点。
