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Theranostics 2019; 9(23):6920-6935. doi:10.7150/thno.35826 This issue Cite

Research Paper

Catalytic inactivation of influenza virus by iron oxide nanozyme

Tao Qin^1,3,5*, Ruonan Ma^1*, Yinyan Yin^2,3, Xinyu Miao¹, Sujuan Chen^1,3,5, Kelong Fan⁴, Juqun Xi², Qi Liu², Yunhao Gu², Yuncong Yin¹, Jiao Hu^1,3,5, Xiufan Liu^1,3,5, Daxin Peng^1,3,5,6✉, Lizeng Gao^2,3,4✉

1. College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, PR China.
2. Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China.
3. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, Jiangsu, 225009, PR China.
4. CAS Engineering Laboratory for Nanozyme, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
5. Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease, Yangzhou, Jiangsu, 225009, PR China.
6. Joint Laboratory Safety of International Cooperation of Agriculture&Agricultural-Products, Yangzhou, Jiangsu 225009, PR China.
^*These authors contributed equally to this work

✉ Corresponding authors: pengdxedu.cn (Daxin Peng) and lzgaoedu.cn (Lizeng Gao)

Abstract

Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus.

Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID₅₀) method. Lipid peroxidation of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting.

Results: We show that IONzymes induce envelope lipid peroxidation and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype.

Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidation of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.

Keywords: Iron oxide nanozyme, lipid peroxidation, lipoxidase-like activity, influenza virus, antivirus

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