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Theranostics 2022; 12(6):2811-2832. doi:10.7150/thno.70098 This issue Cite

Research Paper

Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry

Peiyu Wang^1,2,3,4*, Renwu Zhou^5,6*, Rusen Zhou^5*, Wenshao Li⁷, Janith Weerasinghe⁵, Shuxiong Chen⁸, Bernd H. A. Rehm⁸, Liqian Zhao⁹, Francesca D. Frentiu^3,10, Zhifa Zhang¹, Kexin Yan¹¹, Mary Lor¹¹, Andreas Suhrbier^11,12, Derek J. Richard^3,4, Erik W. Thompson^3,4, Kostya Ken Ostrikov⁵, Xiaofeng Dai^1,13*✉

1. Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
3. School of Biomedical Sciences, Queensland University of Technology, Brisbane 4059, Australia.
4. Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
5. School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia.
6. State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an 710049, PR China.
7. School of Biology and Environmental Science, Queensland University of Technology, Brisbane 4000, Queensland, Australia.
8. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
9. The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
10. Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane 4059, Australia.
11. QIMR Berghofer Medical Research Institute, Herston QLD 4006, Australia.
12. Australian Infectious Disease Research Centre, GVN Center of Excellence, Brisbane, Queensland, Australia.
13. CAPsoul Biotechnology Company, Ltd, Beijing, China
^*These authors contributed equally to this work.

✉ Corresponding author: xiaofeng.daiedu.cn

Abstract

Rational: The mutating SARS-CoV-2 potentially impairs the efficacy of current vaccines or antibody-based treatments. Broad-spectrum and rapid anti-virus methods feasible for regular epidemic prevention against COVID-19 or alike are urgently called for.

Methods: Using SARS-CoV-2 virus and bioengineered pseudoviruses carrying ACE2-binding spike protein domains, we examined the efficacy of cold atmospheric plasma (CAP) on virus entry prevention.

Results: We found that CAP could effectively inhibit the entry of virus into cells. Direct CAP or CAP-activated medium (PAM) triggered rapid internalization and nuclear translocation of the virus receptor, ACE2, which began to return after 5 hours and was fully recovered by 12 hours. This was seen in vitro with both VERO-E6 cells and human mammary epithelial MCF10A cells, and in vivo. Hydroxyl radical (·OH) and species derived from its interactions with other species were found to be the most effective CAP components for triggering ACE2 nucleus translocation. The ERα/STAT3(Tyr705) and EGFR(Tyr1068/1086)/STAT3(Tyr705) axes were found to interact and collectively mediate the effects on ACE2 localization and expression.

Conclusions: Our data support the use of PAM in helping control SARS-CoV-2 if developed into products for nose/mouth spray; an approach extendable to other viruses utilizing ACE2 for host entry.

Keywords: SARS-CoV-2, cold atmospheric plasma (CAP), Plasma activated medium (PAM), Angiotensin-converting enzyme 2

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