Direct Inhibition of SARS-CoV-2 Spike Protein by Peracetic Acid

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.

Efficacy of Peracetic Acid and Sodium Hypochlorite against SARS-CoV-2 on Contaminated Surfaces

“…The first study found that two different PAA-based products (diluted in water) at 173 ppm resulted in 0.2 to 3 log reduction after 10 min of contact time ( 31 ). The second study showed that PAA (diluted in infection media) at 20 ppm resulted in 2 log reduction in SARS-CoV-2 infectivity after 10 min of contact time ( 35 ). We did not test PAA concentrations in suspension with SARS-CoV-2 at 10-min contact time.…”

“…Peracetic acid is a potent microbicide against a broad spectrum of pathogens, and it is widely used in clinical settings to disinfect surfaces and equipment ( 28 , 35 ). Additionally, in the food industry, peracetic acid (PAA) has many uses, including disinfection of equipment, in wash water, and for sanitation of surfaces in contact with organic food ( 36 , 37 ).…”

In Silico Assessment of Chemical Disinfectants on Surface Proteins Unveiled Dissimilarity in Antiviral Efficacy and Suitability towards Pathogenic Viruses

“…The antiviral efficiency of various disinfectants could be comprehensively assessed by complementing binding affinity studies with the analyses of direct, indirect, and multi-faceted actions. Given that predicting the indirect mode of action is lacking, previous studies have primarily focused on binding interactions, providing a foundational approach to understanding how disinfectants function, even for those that act as denaturation reagents [ 28 , 29 ]. Binding affinity studies are instrumental in evaluating the interactions between disinfectants and viral proteins, providing crucial insights into their antiviral mechanisms.…”