PDF(Pubmed)
Abstract：
Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This α-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance antiviral responses. The results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects in a dose-dependent manner, with an EC50 value of 31.19 μM. Myricetin significantly reduced TGEV viral load within 48 h after an 8-h co-incubation period. Further investigations revealed that myricetin at a concentration of 100 μM directly inactivated TGEV and suppressed its intracellular replication stage. Moreover, pretreatment with 100 μM myricetin conferred a protective effect on PK-15 cells against TGEV infection. Myricetin competitively inhibited PLpro with an IC50 value of 6.563 μM. Molecular docking experiments show that myricetin binds to the Cys102 residue of PLpro through conventional hydrogen bonds, Pi-sulfur, and Pi-alkyl interactions. This binding was confirmed through site-directed mutagenesis experiments, indicating myricetin as a potential candidate for preventing and treating TGEV infection.
摘要：
杨梅素,一种在各种食物中发现的天然类黄酮，研究了其对传染性胃肠炎病毒（TGEV）的抗病毒作用。这种α-冠状病毒在全球养猪业造成了巨大的经济损失。这项研究的重点是木瓜蛋白酶(PLpro)，通过介导去泛素化在冠状病毒免疫逃避中起着至关重要的作用。靶向PLpro可能潜在地破坏病毒复制并增强抗病毒反应。结果表明，杨梅素以剂量依赖性方式有效抑制TGEV诱导的细胞病变效应，EC50值为31.19μM。杨梅素在8小时的共同潜伏期后48小时内显着降低了TGEV病毒载量。进一步的研究表明，浓度为100μM的杨梅素直接灭活TGEV并抑制其细胞内复制阶段。此外，用100μM杨梅素预处理对PK-15细胞具有抗TGEV感染的保护作用。杨梅素竞争性抑制PLpro，IC50值为6.563μM。分子对接实验表明，杨梅素通过常规氢键与PLpro的Cys102残基结合，Pi-硫磺,和Pi-烷基相互作用。通过定点诱变实验证实了这种结合，表明杨梅素是预防和治疗TGEV感染的潜在候选者。
