College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Henan Provincial Key Laboratory of Animal Growth and Development Regulation, The Education Department of Henan Provence, Henan Agricultural University, Zhengzhou, Henan Province, PR China.
College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; National Center for International Research, Ministry of Science and Technology, Henan Agricultural University, Zhengzhou, Henan Province, PR China.
Redox Biol. 2020 Sep;36:101601. doi: 10.1016/j.redox.2020.101601. Epub 2020 Jun 8.
Emerging viral pathogens cause substantial morbidity and pose a severe threat to health worldwide. However, a universal antiviral strategy for producing safe and immunogenic inactivated vaccines is lacking. Here, we report an antiviral strategy using the novel singlet oxygen (O)-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated O in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The O produced by LJ002 oxidized lipids in the viral envelope and consequently destroyed the viral membrane structure, thus inhibiting the viral and cell membrane fusion necessary for infection. Moreover, the O-based inactivated pseudorabies virus (PRV) vaccine had no effect on the content of the viral surface proteins. Immunization of mice with LJ002-inactiviated PRV vaccine harboring comparable antigen induced more neutralizing antibody responses and efficient protection against PRV infection than conventional formalin-inactivated vaccine. Additionally, LJ002 inactivated a broad spectrum of enveloped viruses. Together, our results may provide a new paradigm of using broad-spectrum, highly effective inactivants functioning through O-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.
新兴病毒病原体可导致严重的发病率，并对全球健康构成严重威胁。然而，目前缺乏一种普遍的抗病毒策略，以生产安全且具有免疫原性的灭活疫苗。在这里，我们报告了一种使用新型单重态氧（O）生成剂 LJ002 来灭活包膜病毒并提供有效预防病毒感染的抗病毒策略。我们的结果表明，LJ002 可在溶液和活细胞中有效生成 O。然而，LJ002 在体外和体内均未显示出急性毒性的迹象。LJ002 产生的 O 可氧化病毒包膜中的脂质，从而破坏病毒膜结构，从而抑制感染所需的病毒和细胞膜融合。此外，基于 O 的灭活伪狂犬病病毒（PRV）疫苗对病毒表面蛋白的含量没有影响。用 LJ002 灭活的 PRV 疫苗免疫小鼠，其携带的可比抗原诱导了更多的中和抗体反应，并能有效预防 PRV 感染，优于传统的福尔马林灭活疫苗。此外，LJ002 还可灭活广泛的包膜病毒。总之，我们的结果可能为使用广谱、高效的通过 O 介导的脂质氧化作用的灭活剂提供了一种新的范例，以开发针对病毒膜融合过程的抗病毒药物。
