
Background of the Study
The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant global health and economic burdens. The spike (S) protein of SARS-CoV-2 is critical for viral entry into host cells, making it a primary target for therapeutic strategies. While vaccines and antivirals have helped control the virus, researchers continue to explore additional approaches to mitigate its effects. This study investigates whether Nattokinase, a natural enzyme derived from Bacillus subtilis, can degrade the spike protein and potentially contribute to post-COVID health management.
Nattokinase v.s. SARS-CoV-2 Recap
- Nattokinase is an enzyme found in natto, a traditional Japanese fermented soybean dish. It is widely studied for its fibrinolytic and cardiovascular benefits, including anti-thrombotic, anti-inflammatory, and antihypertensive effects. Beyond these properties, its proteolytic activity suggests it may have broader applications such as viral protein degradation.
- The spike protein facilitates SARS-CoV-2 entry into human cells via the ACE2 receptor. It consists of two subunits: S1 subunit, it is responsible for attaching ACE2 through its receptor-binding domain (RBD). S2 subunit, it facilitates viral fusion with host cells, enabling infection. Because of its essential role in infection, targeting the spike protein for degradation potentially inhibits infection or reduces viral persistence in post-COVID scenarios.
Functional Insights - Degradation of Spike protein
This study evaluated the potential of Nattokinase to degrade the SARS-CoV-2 spike protein. The research utilized in vitro experiments, including cell lysates, Western blotting, and immunofluorescence analysis, to assess the enzyme’s effect on the spike protein.
Can Nattokinase degrade the spike protein of SARS-CoV-2?
Does Nattokinase degrade spike protein on the surface of transfected cells?
Is the degradative activity of nattokinase linked to its enzymatic properties?
Does Nattokinase affect ACE2, the key receptor for SARS-CoV-2 entry?
Is Nattokinase safe for human cells?
Key Results
Nattokinase Degrades the SARS-CoV-2 Spike Protein in vitro
- Western blot analysis revealed dose- and time-dependent degradation of the spike protein.
- Higher concentrations (≥500 ng/mL) significantly reduced spike protein levels.
Degradation occurred after 60–180 minutes of incubation.
Nattokinase Degrades Spike Protein on the Cell Surface
- Immunofluorescence analysis showed a clear reduction in spike protein levels on live cells after Nattokinase treatment.
- Cells treated with Nattokinase (2.5–25 µg/mL) exhibited a decrease in spike protein staining.
Activity of Nattokinase is Essential for Spike Protein Degradation
- Heat-inactivated Nattokinase lost its ability to degrade the spike protein, confirming that its enzymatic function is required.
- Protease inhibitors also blocked Nattokinase’s effects, reinforcing its serine protease specificity.
Nattokinase Also Degrades ACE2 in vitro
Western blot experiments showed that Nattokinase degraded not only the spike protein but also ACE2, the receptor for viral entry.
This suggests a dual mechanism where Nattokinase may reduce both the viral protein and its cellular receptor, potentially limiting infection pathways and post entry persistence.
Nattokinase Does Not Harm Healthy Cells
No cytotoxic effects were observed at the tested concentrations.
Even at higher doses (25 µg/mL for 9 hours), Nattokinase did not compromise cell viability, suggesting potential safety in physiological conditions.
Takeaways
This study demonstrates that Nattokinase effectively degrades the SARS-CoV-2 spike protein in vitro, suggesting new possibilities for post-COVID wellness. Taken along with its long history of safe human consumption and its well-documented cardiovascular benefits, Nattokinase becomes a potential natural strategy for supporting recovery and immune resilience in the post-pandemic era.
Reference
Takashi Tanikawa et al., “Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2”, 2022
Full article at: https://doi.org/10.3390/molecules27175405
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