Abstract：
Infectious bursal disease virus (IBDV) is a highly contagious virus with a dsRNA genome, predominantly infecting chickens and causing significant economic losses due to high mortality rates. The emergence of recombinant, novel variant, and highly virulent strains that evade current vaccines has led to frequent epidemics and outbreaks in the poultry industry. The lack of targeted antivirals for IBDV underscores the pressing requirement to develop potent therapeutic options. Within this framework, our research investigated the effectiveness of picroside II, a naturally derived iridoid glycoside, against viruses in DF-1 cells. Our findings demonstrate that picroside II significantly inhibits viral replication, with its efficacy increasing proportionally to the dosage administered. Through time-addition and antiviral duration analysis, we determined that picroside II therapeutically blocks IBDV replication, with its effects persisting for over 72 hours. Further investigation revealed that picroside II specifically inhibits the cellular replication stage of IBDV\'s lifecycle. Additionally, our findings indicate that picroside II impairs VP1 polymerase activity by binding to the active pocket, which significantly disrupts the interaction between VP1 and VP3. Mutations at three critical binding sites on VP1 not only impair virus replication but also hinder polymerase function and disrupt VP1-VP3 interactions. Collectively, these results demonstrate that picroside II, by inhibiting viral polymerase activity, represents a promising antiviral agent against IBDV.
摘要：
传染性法氏囊病病毒（IBDV）是一种高度传染性的病毒，具有dsRNA基因组，主要感染鸡，并由于高死亡率造成重大的经济损失。重组的出现，新颖的变体，逃避当前疫苗的高毒株导致家禽业频繁流行和爆发。缺乏针对IBDV的靶向抗病毒药物强调了开发有效治疗选择的迫切需求。在这个框架内,我们的研究调查了胡黄连苷II的有效性，一种天然衍生的环烯醚萜苷，对抗DF-1细胞中的病毒。我们的研究结果表明，胡黄连苷II显著抑制病毒复制，其功效与给药剂量成比例增加。通过时间添加和抗病毒持续时间分析，我们确定胡黄连苷II治疗性阻断IBDV复制，其效果持续超过72小时。进一步的研究表明，胡黄连苷II特异性抑制IBDV生命周期的细胞复制阶段。此外,我们的发现表明，胡黄连苷II通过与活性口袋结合而损害VP1聚合酶活性，这显著破坏了VP1和VP3之间的相互作用。VP1上三个关键结合位点的突变不仅损害病毒复制，而且阻碍聚合酶功能并破坏VP1-VP3相互作用。总的来说，这些结果表明，胡黄连苷II，通过抑制病毒聚合酶活性，代表针对IBDV的有希望的抗病毒剂。
