Du Xiaowen, Zeng Mengting, Yang Wenzhuo, Jiang Yuting, Huang Guangyu, Ding Shiping, Jiang Danli, Yuan Zhaoxia
College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510642, China.
These authors contributed equally.
Avian Dis. 2025 Jun;69(2):152-159. doi: 10.1637/aviandiseases-D-24-00083.
For decades, infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), has posed a significant threat to poultry health and is mainly controlled by vaccines. However, the currently available commercial vaccines do not provide adequate protection against new IBV strains that emerge due to ongoing evolution. Therefore, new antiviral strategies need to be explored. Cepharanthine (CEP), tetrandrine (TET), and berbamine hydrochloride (BBM) are natural plant-derived bis-benzylisoquinoline alkaloids (BBAs) with proven antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), porcine epidemic diarrhea virus (PEDV), and other viruses. Despite this, their potential antiviral activities against IBV remain unknown. As a proof-of-concept study, we aimed to investigate the inhibitory effects of CEP, TET, and BBM on the laboratory-adapted IBV Beaudette strain in Vero cells and of CEP in chicken embryos. Our research demonstrated that CEP, TET, and BBM effectively suppressed IBV infection in Vero cells, with CEP showing a particularly high selective index of 309.6. These compounds dose-dependently decreased IBV RNA levels and N protein expression and lowered intracellular and extracellular viral titers. Notably, CEP also exhibited antiviral activity against IBV infection in chicken embryos, resulting in reduced mortality and fewer lesions. While these findings highlight the potential of CEP, TET, and BBM as candidates for further development, further studies are required to evaluate their efficacy against field-prevalent IBV strains (e.g., Massachusetts, QX-like) and clarify the specific antiviral mechanisms.
几十年来，由传染性支气管炎病毒（IBV）引起的传染性支气管炎（IB）对家禽健康构成了重大威胁，主要通过疫苗进行控制。然而，目前可用的商业疫苗并不能为抵御因病毒不断进化而出现的新型IBV毒株提供充分保护。因此，需要探索新的抗病毒策略。千金藤素（CEP）、粉防己碱（TET）和盐酸小檗胺（BBM）是天然植物来源的双苄基异喹啉生物碱（BBA），已被证明对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、猪流行性腹泻病毒（PEDV）和其他病毒具有抗病毒活性。尽管如此，它们对IBV的潜在抗病毒活性仍不清楚。作为一项概念验证研究，我们旨在研究CEP、TET和BBM对Vero细胞中实验室适应的IBV Beaudette毒株的抑制作用以及CEP对鸡胚的抑制作用。我们的研究表明，CEP、TET和BBM能有效抑制Vero细胞中的IBV感染，其中CEP的选择性指数特别高，达到309.6。这些化合物剂量依赖性地降低了IBV RNA水平和N蛋白表达，并降低了细胞内和细胞外病毒滴度。值得注意的是，CEP对鸡胚中的IBV感染也表现出抗病毒活性，从而降低了死亡率并减少了病变。虽然这些发现突出了CEP、TET和BBM作为进一步开发候选药物的潜力，但仍需要进一步研究来评估它们对田间流行的IBV毒株（如马萨诸塞州毒株、QX样毒株）的疗效，并阐明具体的抗病毒机制。
