The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20 % (±2.88 %), 46.24 % (±1.79 %), and 91.71 % (±0.47 %), respectively. Additionally, determination of PAW's physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.
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