As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, Au@Ag nanorods (Au@AgNRs) were successfully synthesized by coating AuNRs with silver and were shown for the first time to have activity against the replication of porcine epidemic diarrhea virus (PEDV). Viral titer analysis demonstrated that Au@AgNRs could inhibit PEDV infection by 4 orders of magnitude at 12 h post-infection, which was verified by viral protein expression analysis. The potential mechanism of action showed that Au@AgNRs could inhibit the entry of PEDV and decrease the mitochondrial membrane potential and caspase-3 activity. Additionally, we demonstrated that a large amount of virus proliferation can cause the generation of reactive oxygen species in cells, and the released Ag⁺ and exposed AuNRs by Au@AgNRs after the stimulation of reactive oxygen species has superior antiviral activity to ensure long-term inhibition of the PEDV replication cycle. The integrated results support that Au@AgNRs can serve as a potential therapeutic strategy to prevent the replication of coronavirus.

中文翻译：

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通过多位点机制具有持久抑制冠状病毒繁殖的金/银杂化纳米粒子

冠状病毒作为一种大型的包膜RNA病毒，具有重要的医学和兽医学意义，由于其生物多样性和快速可变性，抗冠状病毒的治疗也具有挑战性。在这项研究中，通过用银包被AuNRs成功地合成了Au @ Ag纳米棒（Au @ AgNRs），并且首次证明其对猪流行性腹泻病毒（PEDV）的复制具有活性。病毒滴度分析表明，Au @ AgNRs可以在感染后12 h将PEDV感染抑制4个数量级，这已通过病毒蛋白表达分析得到证实。潜在的作用机制表明，Au @ AgNRs可以抑制PEDV的进入并降低线粒体膜电位和caspase-3活性。另外，活性氧的刺激后，Au @ AgNRs的⁺和暴露的AuNRs具有优异的抗病毒活性，以确保PEDV复制周期的长期抑制。综合结果支持Au @ AgNRs可以作为防止冠状病毒复制的潜在治疗策略。