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Infectivity and structure of SARS-CoV-2 after hydrogen peroxide treatment
Saba R Aliyari1, Guodong Xie1,2, Xian Xia1,2
1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Mbio
|April 21, 2025
Summary
Hydrogen peroxide (H2O2) rapidly inactivates SARS-CoV-2 by locking its spike protein in a pre-fusion state, unlike paraformaldehyde which promotes a post-fusion conformation. This study reveals H2O2’s antiviral mechanism and efficacy.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Hydrogen peroxide (H2O2) is a broad-spectrum antiviral agent with uncharacterized activity against SARS-CoV-2.
- Its mechanism of action against SARS-CoV-2 remains poorly understood.
Purpose of the Study:
- To evaluate the antiviral activity of H2O2 against SARS-CoV-2.
- To investigate the structural impact of H2O2 on the SARS-CoV-2 virion compared to paraformaldehyde (PFA).
Main Methods:
- SARS-CoV-2 antiviral assays to determine the half-maximal inhibitory concentration (IC50).
- Cryogenic electron tomography (cryo-ET) with subtomogram averaging to analyze viral structural changes.
- Biochemical analysis of spike protein conformation.
Main Results:
- H2O2 rapidly inactivates SARS-CoV-2 with an IC50 of 0.0015%.
- PFA treatment induced a post-fusion conformation of the spike (S) protein.
- H2O2 treatment locked the S protein in a pre-fusion conformation, likely via cysteine oxidation.
Conclusions:
- H2O2 effectively inactivates SARS-CoV-2 in tissue culture by stabilizing the pre-fusion spike conformation.
- This mechanism prevents viral entry into host cells.
- Findings support H2O2 as a disinfectant and suggest potential for targeted antiviral therapies.
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