Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores’ ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.

中文翻译：

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聚醚离子载体的抗冠状病毒潜力：兽用抗生素在牲畜中的新应用

冠状病毒一直是全球畜牧业和公共卫生领域的主要关注点。然而，目前缺乏具有广谱抗病毒活性的有效药物来应对新出现的突变株或耐药性带来的挑战。此外，识别多靶点药物的方法也不足。在开发针对各种冠状病毒的有效药物中，氨基肽酶 N (APN) 和 3C 样蛋白酶 (3CLpro) 分别代表了宿主导向和病毒导向策略的有希望的靶标。在这项研究中，马杜霉素铵通过针对这两种蛋白质表现出广谱抗病毒作用。两种靶蛋白配体的 4 Å 结合域具有结构相似性，表明基于这些结构域筛选和设计药物可能表现出广谱且高效的抗病毒活性。此外，还发现聚醚离子载体携带锌离子的能力可能是它们能够靶向APN并表现出抗病毒作用的原因之一。该实验结果为未来的药物筛选和设计提供了新的视角，同时也为聚醚离子载体在牲畜健康管理中的应用提供了有价值的参考。