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Direct Inhibition of SARS-CoV-2 Spike Protein by Peracetic Acid
Yuichiro Yamamoto1, Yoshio Nakano2, Mana Murae1,3
1Laboratory of Molecular Targeted Therapy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Chiba, Japan.
Abstract:
Peracetic acid (PAA) disinfectants are effective against a wide range of pathogenic microorganisms, including bacteria, fungi, and viruses. Several studies have shown the efficacy of PAA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, its efficacy in SARS-CoV-2 variants and the molecular mechanism of action of PAA against SARS-CoV-2 have not been investigated. SARS-CoV-2 infection depends on the recognition and binding of the cell receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the spike protein. Here, we demonstrated that PAA effectively suppressed pseudotyped virus infection in the Wuhan type and variants, including Delta and Omicron. Similarly, PAA reduced the authentic viral load of SARS-CoV-2. Computational analysis suggested that the hydroxyl radicals produced by PAA cleave the disulfide bridges in the RBD. Additionally, the PAA treatment decreased the abundance of the Wuhan- and variant-type spike proteins. Enzyme-linked immunosorbent assay showed direct inhibition of RBD-ACE2 interactions by PAA. In conclusion, the PAA treatment suppressed SARS-CoV-2 infection, which was dependent on the inhibition of the interaction between the spike RBD and ACE2 by inducing spike protein destabilization. Our findings provide evidence of a potent disinfection strategy against SARS-CoV-2.
Insights
Peracetic acid (PAA) effectively combats SARS-CoV-2 variants by disrupting spike protein binding to ACE2 receptors. This disinfectant shows potent action against the virus, offering a promising disinfection strategy.
Area of Science:
- Virology
- Microbiology
- Biochemistry
Background:
- Peracetic acid (PAA) is a broad-spectrum disinfectant effective against various pathogens.
- Previous studies confirm PAA's efficacy against SARS-CoV-2, but its action against variants and molecular mechanisms remain unclear.
- SARS-CoV-2 entry into cells relies on the spike protein's receptor-binding domain (RBD) interacting with ACE2.
Purpose of the Study:
- To investigate the efficacy of PAA against SARS-CoV-2 variants (Delta, Omicron).
- To elucidate the molecular mechanism of PAA's antiviral action against SARS-CoV-2.
- To assess PAA's potential as a disinfection strategy against SARS-CoV-2.
Main Methods:
- Testing PAA against pseudotyped and authentic SARS-CoV-2 strains, including variants.
- Employing computational analysis to predict PAA's interaction with the spike protein RBD.
- Utilizing enzyme-linked immunosorbent assays (ELISA) to evaluate RBD-ACE2 binding inhibition.
Main Results:
- PAA significantly suppressed pseudotyped virus infections across Wuhan, Delta, and Omicron variants.
- PAA treatment reduced the viral load of authentic SARS-CoV-2.
- Computational and experimental data indicated PAA destabilizes the spike protein RBD, inhibiting ACE2 binding.
Conclusions:
- PAA effectively inhibits SARS-CoV-2 infection, including variants, by disrupting the spike protein RBD-ACE2 interaction.
- The mechanism involves PAA-induced destabilization of the spike protein.
- PAA presents a potent disinfection strategy against SARS-CoV-2.
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