School of Pharmaceutical Sciences, Shenzhen University, Shenzhen, 518060, China.
College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, China.
Virus Res. 2022 Aug;317:198816. doi: 10.1016/j.virusres.2022.198816. Epub 2022 May 19.
Group B coxsackievirus is an enterovirus that can cause a variety of diseases, including myocarditis, aseptic meningitis, and hand, foot, and mouth disease. Currently, there is no effective antiviral drug against this virus. In this study, we used a cytopathic effect-based viral inhibition assay to screen an FDA-approved drug library and found that doxepin hydrochloride had potential antiviral activity. Doxepin hydrochloride exhibited strong antiviral activity against coxsackievirus B types 1-3 with a 50% inhibitory concentration of 10.12 ± 0.85 μM. Moreover, doxepin hydrochloride did not exert antiviral activity against other enteroviruses, including enterovirus A71 (subtypes BrCr/C4) and coxsackievirus A (subtypes 6/10/16). Furthermore, doxepin hydrochloride inhibited virus replication in the early stage of the infection cycle rather than affecting the entry or assembly process. In addition, a few mechanism-related pharmacophores were discovered through gene association network analysis. These findings identify a possible lead compound for treating coxsackievirus B infection and simultaneously offer valuable clues for drug repositioning.
B 组柯萨奇病毒是一种肠病毒，可引起多种疾病，包括心肌炎、无菌性脑膜炎和手足口病。目前，尚无针对该病毒的有效抗病毒药物。在这项研究中，我们使用基于细胞病变效应的病毒抑制试验筛选了一个 FDA 批准的药物库，发现盐酸多塞平具有潜在的抗病毒活性。盐酸多塞平对柯萨奇病毒 B 型 1-3 具有很强的抗病毒活性，其 50%抑制浓度为 10.12±0.85 μM。此外，盐酸多塞平对其他肠道病毒（包括肠道病毒 A71（亚型 BrCr/C4）和柯萨奇病毒 A（亚型 6/10/16））没有抗病毒活性。此外，盐酸多塞平在感染周期的早期抑制病毒复制，而不影响进入或组装过程。此外，通过基因关联网络分析发现了一些与机制相关的药效团。这些发现为治疗柯萨奇病毒 B 感染提供了一个可能的先导化合物，同时为药物再定位提供了有价值的线索。
