An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals
An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals
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基于单线态氧介导的脂质氧化的有效灭活剂暗示了广谱抗病毒药物的新范例
DOI：
10.1016/j.redox.2020.101601
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发表时间：
2020-09-01
期刊：
影响因子：
11.4
通讯作者：
Chu, Bei-Bei
中科院分区：
文献类型：
--
作者：
Zeng, Lei;Wang, Meng-Di;Chu, Bei-Bei
新出现的病毒病原体导致大量发病率，并对全世界的健康构成严重威胁。然而，缺乏生产安全和免疫原性灭活疫苗的通用抗病毒战略。在这里，我们报告了一种使用新型单线态氧(O-1(2))生成剂LJ002来灭活包膜病毒并提供有效保护以对抗病毒感染的抗病毒策略。我们的结果表明，LJ002在溶液和活细胞中有效地产生了O-1(2)。然而，LJ002在体外和体内都没有表现出急性毒性的迹象。LJ002产生的O-1(2)氧化了病毒被膜中的脂类，从而破坏了病毒的膜结构，从而抑制了感染所必需的病毒与细胞膜的融合。O-1(2)伪狂犬病灭活疫苗对病毒表面蛋白含量无明显影响。与常规福尔马林灭活疫苗相比，携带类似抗原的LJ002 PRV灭活疫苗免疫小鼠可诱导更多的中和抗体应答，并有效地预防PRV感染。此外，LJ002灭活了广泛范围的包膜病毒。总之，我们的结果可能提供一个新的范例，使用广谱、高效的灭活剂，通过O-1(2)介导的脂质氧化发挥作用，开发针对病毒膜融合过程的抗病毒药物。
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-1(2))-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated O-1(2) in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The O-1(2) 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-1(2)-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-1(2)-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.