Liang Jixiang, Xu Weihang, Gou Fang, Qin Liangni, Yang Hongfei, Xiao Jiaxu, Li Long, Zhang Wanpo, Peng Dapeng
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People's Republic of China; National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, Hubei, 430070, People's Republic of China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, People's Republic of China.
Virology. 2024 Sep;597:110128. doi: 10.1016/j.virol.2024.110128. Epub 2024 Jun 1.
Porcine epidemic diarrhea virus (PEDV) remains one of the major causative microorganisms of viral diarrhea in piglets worldwide, with no approved drugs for treatment. We identified a natural molecule, flavonol, which is widely found in tea, vegetables and herbs. Subsequently, the antiviral activity of compound flavonol was evaluated in Vero cells and IPEC-J2 cells, and its anti-PEDV mechanism was analyzed by molecular docking and molecular dynamics. The results showed that flavonol could effectively inhibit viral progeny production, RNA synthesis and protein expression of PEDV strains in a dose-dependent manner. When flavonol was added simultaneously with viral infection in Vero cells, it demonstrated potent anti-PEDV activity by affecting the viral attachment and internalization phases. Similarly, in IPEC-J2 cells, flavonol effectively inhibited PEDV infection at different stages of infection, except for the release phase. Moreover, flavonol mainly interacts with PEDV M through hydrogen bonds and hydrophobic forces, and the complex formed by it has high stability. Importantly, flavonol also showed broad-spectrum activity against other porcine enteric coronaviruses such as TGEV and PDCoV in vitro. These findings suggest that flavonol may exert antiviral effects by interacting with viral M, thereby affecting viral replication. This means that flavonol is expected to become a potential drug to prevent or treat porcine enteric coronavirus.
猪流行性腹泻病毒（PEDV）仍然是全球仔猪病毒性腹泻的主要致病微生物之一，目前尚无获批的治疗药物。我们鉴定出一种天然分子黄酮醇，它广泛存在于茶、蔬菜和草药中。随后，在Vero细胞和IPEC-J2细胞中评估了黄酮醇化合物的抗病毒活性，并通过分子对接和分子动力学分析了其抗PEDV机制。结果表明，黄酮醇能以剂量依赖的方式有效抑制PEDV毒株的子代病毒产生、RNA合成和蛋白质表达。当在Vero细胞中与病毒感染同时添加黄酮醇时，它通过影响病毒附着和内化阶段表现出强大的抗PEDV活性。同样，在IPEC-J2细胞中，黄酮醇在感染的不同阶段有效抑制PEDV感染，但释放阶段除外。此外，黄酮醇主要通过氢键和疏水作用力与PEDV M相互作用，并且由其形成的复合物具有高稳定性。重要的是，黄酮醇在体外对其他猪肠道冠状病毒如TGEV和PDCoV也表现出广谱活性。这些发现表明，黄酮醇可能通过与病毒M相互作用发挥抗病毒作用，从而影响病毒复制。这意味着黄酮醇有望成为预防或治疗猪肠道冠状病毒的潜在药物。
