Diyuan Yang , Jing Ning , Yuyu Zhang , Xuehua Xu , Dongwei Zhang , Huifeng Fan , Jing Wang , Gen Lu
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引用次数: 0
Abstract
Adenoviral infections, particularly in children, remain a significant public health issue with no approved targeted treatments. Artemisinin and its derivatives, well-known for their use in malaria treatment, have shown antiviral activities in recent studies. However, their efficacy against human adenovirus (HAdV) remains unexplored. This study aimed to assess the activity of artemisinin and its derivatives against HAdV infection in vitro using cell lines and primary cells. Our data revealed that artemisinin exhibited dose-dependent anti-HAdV activity with no apparent cytotoxicity over a wide concentration range. Mechanistically, artemisinin did not affect viral attachment or entry into target cells, nor the viral genome entry into cell nucleus. Instead, it inhibited HAdV through suppression of viral DNA replication. Comparative analysis with its derivatives, artesunate and artemisone, showed distinct cytotoxicity and anti-adenoviral profiles, with artemisone showing superior efficacy and lower toxicity. Further validation using a primary airway epithelial cell model confirmed the anti-adenoviral activity of both artemisinin and artemisone against different virus strains. Together, our findings suggest that artemisinin and its derivatives may be promising candidates for anti-HAdV treatment.
腺病毒感染,尤其是儿童的腺病毒感染,仍然是一个重大的公共卫生问题,目前还没有获得批准的靶向治疗方法。青蒿素及其衍生物因用于治疗疟疾而闻名,在最近的研究中显示出了抗病毒活性。然而,它们对人类腺病毒(HAdV)的疗效仍有待探索。本研究旨在利用细胞系和原代细胞评估青蒿素及其衍生物在体外抗HAdV感染的活性。我们的数据显示,青蒿素具有剂量依赖性的抗HAdV活性,在很宽的浓度范围内没有明显的细胞毒性。从机理上讲,青蒿素不影响病毒附着或进入靶细胞,也不影响病毒基因组进入细胞核。相反,它是通过抑制病毒 DNA 复制来抑制 HAdV 的。与青蒿素的衍生物青蒿琥酯和青蒿酮的比较分析表明,青蒿素具有不同的细胞毒性和抗腺病毒特性,其中青蒿酮的疗效更好,毒性更低。使用原发性气道上皮细胞模型进行的进一步验证证实了青蒿素和青蒿酮对不同病毒株的抗腺病毒活性。总之,我们的研究结果表明,青蒿素及其衍生物可能是抗HAdV治疗的理想候选药物。
期刊介绍:
Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.