Diphyllin’s Two-Way Defense Against COVID-19 Infections

Herbs and Phytochemicals: A group of researchers has discovered a promising new phytochemical that offers hope in the fight against COVID-19. This phytochemical, known as diphyllin, could potentially block the entry of the virus into human cells. The study, conducted by teams from Chongqing Medical University in China and the University of Duisburg-Essen in Germany, reveals that diphyllin launches a dual attack against SARS-CoV-2 by inhibiting two important proteins, cathepsin L and furin. These findings offer insight into a new therapeutic approach for treating COVID-19 and its variants.


Diphyllin’s Two-Way Defense Against COVID-19 Infections

The Need for Effective Treatments
Since the emergence of COVID-19, the global scientific community has been striving to find effective treatments. Vaccines have now been shown to be non-effective in preventing the spread of the virus and is causing lots of adverse issues in recipients. This has resulted in an urgent demand for antiviral drugs that can treat the disease and prevent severe illness, especially among high-risk populations such as the elderly and immunocompromised.
 
In this Herbs and Phytochemicals news report, we will explore the findings of the study, which investigates how diphyllin works to prevent the virus from entering cells and potentially provides a new pathway for COVID-19 treatment.
 
What is Diphyllin
Diphyllin is a naturally occurring arylnaphthalide lignan derived from tropical plants, widely valued in traditional Chinese medicine. Typically, diphyllin is an arylnaphthalene lactone that is most commonly isolated from the leaves of Astilboides tabularis, though it is also present in various other medicinal plants. This compound is recognized for its strong inhibitory effects on vacuolar (H+)-ATPases, which play a critical role in endosomal acidification. This process is essential for many enveloped viruses to initiate their infection pathways after entering host cells via receptor-mediated endocytosis.
 
How Diphyllin Works
SARS-CoV-2, the virus responsible for COVID-19, enters human cells through two key routes: the endosomal route and the cell surface route. To do this, the virus uses its spike protein, which must be activated by enzymes in the human body before the virus can fuse with the host cell. Two such enzymes, cathepsin L and furin, play essential roles in this process.
 
Diphyllin has been shown to inhibit the activity of both cathepsin L and furin. By doing so, it blocks the virus from entering cells through both the endosomal and surface pathways. This dual action represents a significant breakthrough in antiviral treatment, as it targets multiple points in the viral infection process, making it more difficult for the virus to adapt and bypass the drug’s effects.
 
Key Findings of the Study
The study demonstrates that diphyllin can inhibit the entry of multiple SARS-CoV-2 variants, including Alpha, Beta, Delta, and Omicron, into human cells . The phytochemical was tested on several cell types, including lung cells, which are the primary target of the virus.
 
The researchers found that diphyllin effectively blocked the virus from entering cells by inhibiting cathepsin L, an enzyme that the virus uses to enter cells through the endosomal pathway. In addition, diphyllin also reduced the activity of furin, an enzyme responsible for activating the spike protein at the cell surface. By targeting both of these enzymes, diphyllin was able to prevent the virus from entering cells through either route.
 
One of the most promising aspects of diphyllin’s action is its ability to inhibit a wide range of SARS-CoV-2 variants. In the study, the drug was shown to be effective against the original strain of the virus, as well as several variants of concern. The Omicron variant, in particular, which has been known for its increased transmissibility, was significantly inhibited by diphyllin. This suggests that the drug could be a valuable tool in combating future variants of the virus.
 
Testing in Human Cells
The study also included experiments using human primary tracheal epithelial cells, which closely mimic the cells found in the human airway. This model is considered more representative of how the virus behaves in the human body compared to traditional cell lines.
 
In these experiments, diphyllin demonstrated strong antiviral activity, significantly reducing the replication of the virus in the cells. The results suggest that diphyllin could be an effective treatment for COVID-19 in humans, although further clinical studies are needed to confirm these findings.
 
Potential Advantages of Diphyllin
One of the key advantages of diphyllin is its dual mechanism of action. Most antiviral drugs target a single point in the viral life cycle, but diphyllin inhibits two separate enzymes that are both essential for viral entry. This makes it more difficult for the virus to develop resistance to the drug, as it would need to overcome two different barriers to successfully infect cells.
 
Moreover, diphyllin is a naturally occurring compound, which could make it easier to produce at a large scale. The drug has also been shown to have a good safety profile, with minimal toxicity to human cells at the concentrations used in the study.
 
The Next Steps
While the results of this study are promising, more research is needed before diphyllin can be used as a treatment for COVID-19. Clinical trials will be required to determine the safety and efficacy of the drug in humans. Additionally, researchers will need to investigate whether diphyllin can be used in combination with other antiviral drugs or treatments to improve its effectiveness.

The study’s authors are optimistic that diphyllin could be developed into a new treatment for COVID-19, particularly for patients who are at high risk of severe illness or who have not responded well to existing treatments.
 
Conclusion
The discovery of diphyllin’s ability to block SARS-CoV-2 entry into human cells represents an important step forward in the fight against COVID-19. By targeting both cathepsin L and furin, diphyllin offers a two-pronged approach to preventing viral infection, making it a promising candidate for further research and development.
 
In addition to its potential as a treatment for COVID-19, diphyllin’s broad-spectrum antiviral activity suggests that it could be useful in treating other viral infections as well. As researchers continue to explore the possibilities of this compound, there is hope that it could become a valuable tool in the ongoing battle against the COVID-19 pandemic and future viral outbreaks.
 
The study findings were published in the peer-reviewed journal: Virus Research.
https://www.sciencedirect.com/science/article/pii/S0168170224001783
 
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