College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China.
J Virol. 2024 Jul 23;98(7):e0041323. doi: 10.1128/jvi.00413-23. Epub 2024 Jun 12.
Porcine epidemic diarrhea virus (PEDV) is a type A coronavirus that causes severe watery diarrhea in piglets, resulting in severe economic losses worldwide. Therefore, new approaches to control PEDV infection are essential for a robust and sustainable pig industry. We screened 314 small-molecule drug libraries provided by Selleck and found that four drugs had obviously inhibitory effects on PEDV in Vero cells. PA-824, which had the highest SI index and the most reliable clinical safety, was selected for experiments. Animal attack tests showed that PA-824 effectively alleviated the clinical signs, intestinal pathological changes, and inflammatory responses in lactating piglets after PEDV infection. To further investigate the antiviral mechanism of PA-824, we measured the inhibitory effect of PA-824 on PEDV proliferation in a dose-dependent manner. By exploring the effect of PA-824 on the PEDV life cycle, we found that PA-824 acted directly on viral particles and hindered the adsorption, internalization, and replication phases of the virus, followed by molecular docking analysis to predict the interaction between PA-824 and PEDV non-structural proteins. Finally, we found that PA-824 could inhibit the apoptotic signaling pathway by suppressing PEDV-induced p53 activation. These results suggest that PA-824 could be protective against PEDV infection in piglets and could be developed as a drug or a feed additive to prevent and control PEDV diseases.IMPORTANCEPEDV is a highly contagious enteric coronavirus that widely spread worldwide, causing serious economic losses. There is no drug or vaccine to effectively control PEDV. In this study, we found that PA-824, a compound of mycobacteria causing pulmonary diseases, inhibited PEDV proliferation in both and . We also found that PA-824 directly acted on viral particles and hindered the adsorption, internalization, and replication stages of the virus. In addition, we found that PA-824 could inhibit the apoptotic signaling pathway by inhibiting PEDV-induced p53 activation. In conclusion, it is expected to be developed as a drug or a feed additive to prevent and control PEDV diseases.
猪流行性腹泻病毒（PEDV）是一种 A 型冠状病毒，可导致仔猪出现严重的水样腹泻，在全球范围内造成严重的经济损失。因此，寻找新的方法来控制 PEDV 感染对于一个稳健且可持续的养猪业至关重要。我们筛选了 Selleck 提供的 314 种小分子药物库，发现其中 4 种药物在 Vero 细胞中对 PEDV 具有明显的抑制作用。PA-824 的 SI 指数最高，临床安全性最可靠，因此被选择用于进一步实验。动物攻毒试验表明，PA-824 可有效缓解感染 PEDV 后哺乳仔猪的临床症状、肠道病理变化和炎症反应。为了进一步研究 PA-824 的抗病毒机制，我们以剂量依赖的方式测定了 PA-824 对 PEDV 增殖的抑制作用。通过探索 PA-824 对 PEDV 生命周期的影响，我们发现 PA-824 直接作用于病毒颗粒，阻碍病毒的吸附、内化和复制阶段，随后进行分子对接分析以预测 PA-824 与 PEDV 非结构蛋白的相互作用。最后，我们发现 PA-824 可以通过抑制 PEDV 诱导的 p53 激活来抑制凋亡信号通路。这些结果表明，PA-824 可以保护仔猪免受 PEDV 感染，可将其开发为一种药物或饲料添加剂，以预防和控制 PEDV 疾病。
PEDV 是一种高度传染性的肠冠状病毒，在全球范围内广泛传播，造成严重的经济损失。目前尚无有效控制 PEDV 的药物或疫苗。在本研究中，我们发现，引起肺部疾病的分枝杆菌化合物 PA-824 可抑制 和 中的 PEDV 增殖。我们还发现，PA-824 直接作用于病毒颗粒，阻碍病毒的吸附、内化和复制阶段。此外，我们发现，PA-824 通过抑制 PEDV 诱导的 p53 激活来抑制凋亡信号通路。总之，有望将其开发为一种药物或饲料添加剂，以预防和控制 PEDV 疾病。
