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  3. 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

  • Redox Biol. 2020 Sep;36:101601. doi: 10.1016/j.redox.2020.101601.
Lei Zeng 1,  Meng-Di Wang 1,  Sheng-Li Ming 1,  Guo-Li Li 1,  Peng-Wei Yu 1,  Yan-Li Qi 1,  Da-Wei Jiang 2,  Guo-Yu Yang 3,  Jiang Wang 4,  Bei-Bei Chu 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: haubiochem@163.com.
  • 4 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. Electronic address: wangjiang_hau@hotmail.com.
  • 5 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; National Center for International Research, Ministry of Science and Technology, Henan Agricultural University, Zhengzhou, Henan Province, PR China. Electronic address: chubeibei_hau@hotmail.com.
PMID: 32535542 DOI: 10.1016/j.redox.2020.101601
Abstract

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 (1O2)-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral Infection. Our results demonstrated that LJ002 efficiently generated 1O2 in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The 1O2 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 1O2-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 1O2-mediated lipid oxidation for developing antivirals that target the viral membrane fusion process.

Keywords

Broad-spectrum antivirals; Immunization; Inactivated virus vaccine; Lipid oxidation; Membrane fusion; Singlet oxygen.

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