1. An effective inactivant based on singlet oxygen-mediated lipid oxidation implicates a new paradigm for broad-spectrum antivirals.
- Author
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Zeng L, Wang MD, Ming SL, Li GL, Yu PW, Qi YL, Jiang DW, Yang GY, Wang J, and Chu BB
- Subjects
- Animals, Antiviral Agents pharmacology, Mice, Vaccines, Inactivated, Virus Internalization, Singlet Oxygen, Virus Diseases
- 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 (
1 O2 )-generating agent LJ002 to inactivate enveloped viruses and provide effective protection against viral infection. Our results demonstrated that LJ002 efficiently generated1 O2 in solution and living cells. Nevertheless, LJ002 exhibited no signs of acute toxicity in vitro or in vivo. The1 O2 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, the1 O2 -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 through1 O2 -mediated lipid oxidation for developing antivirals that target the viral membrane fusion process., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2020
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