Protein from Bitter Melon inhibits SARS-CoV-2 infection

Medical News: The ongoing global fight against COVID-19 has led to significant advancements in understanding how to block the virus from infecting human cells. In a recent groundbreaking study, researchers from Morehouse School of Medicine-USA, the National Cancer Institute-USA, and Senegal's PROMETRA International have explored the antiviral properties of a protein known as MoMo30, derived from the bitter melon Momordica balsamina. This Medical News report delves into the study's key findings and their potential implications for COVID-19 treatments.


Protein from Bitter Melon inhibits SARS-CoV-2 infection

MoMo30: A Traditional Remedy with Modern Potential
The study draws on traditional medicine from Senegal, where extracts of Momordica balsamina have long been used to treat various infections. Researchers isolated MoMo30 from the plant and explored its effects against the COVID-19 virus. The study focuses on how MoMo30 interacts with the virus’s spike protein, which is essential for the virus to infect human cells. The researchers aimed to determine if this protein could inhibit the virus, specifically looking at the pseudovirus form of SARS-CoV-2. This discovery is part of a broader effort to scientifically validate traditional remedies.
 
How the Spike Protein Facilitates Infection
COVID-19 is caused by SARS-CoV-2, a virus that uses its spike protein to bind to the ACE2 receptors on human cells. The spike protein consists of two subunits, S1 and S2, which play crucial roles in the virus’s ability to attach to and enter cells. The S1 subunit binds to the receptor, while the S2 subunit facilitates membrane fusion, allowing the virus to inject its genetic material into the host cell. The study sought to understand whether MoMo30 could block this process by interacting with the spike protein.
 
Inhibiting Virus Fusion with MoMo30
In their experiments, the researchers demonstrated that MoMo30 interacts directly with the spike protein of multiple variants of SARS-CoV-2, including the original WH-1 strain, as well as Alpha, Delta, and Omicron variants. They found that MoMo30 binds to both the S1 and S2 domains of the spike protein, but not the receptor-binding domain (RBD). This distinction is critical as it suggests that MoMo30 interferes with a later stage of the virus’s entry into human cells, likely by preventing the fusion of the virus with the cell membrane.
 
The study highlights that MoMo30’s mechanism of action differs from that of antibodies or other treatments targeting the receptor-binding domain. Instead of blocking the virus from attaching to the cell, MoMo30 likely inhibits the structural changes required for the virus to fuse with the cell membrane. This unique approach could make MoMo30 a valuable addition to the growing arsenal of COVID-19 treatments.
 
The Role of Pseudoviruses in Testing
To test MoMo30’s efficacy, the researchers developed pseudoviruses - non-infectious virus particles that mimic the structure of SARS-CoV-2. T hese pseudoviruses express the spike protein and can be used to measure the impact of various compounds on viral entry. The study used a luciferase reporter assay to determine how effectively MoMo30 inhibits the pseudovirus from infecting human cells.
 
The results showed that even low concentrations of MoMo30 were effective in blocking pseudovirus infection. The researchers calculated the IC50 value (the concentration required to inhibit 50% of the virus) and found that MoMo30 had a potent inhibitory effect at both crude and purified levels. These findings suggest that MoMo30 could be developed as a therapeutic agent to prevent COVID-19 infections.
 
Safe and Non-Toxic
In addition to its antiviral properties, the researchers also assessed MoMo30’s safety profile using an XTT cytotoxicity assay. This assay measures the potential toxic effects of MoMo30 on human cells. The study found that MoMo30 was non-toxic at the concentrations required for antiviral activity, making it a promising candidate for further development.
 
The study also examined whether the tannins in the Momordica balsamina extracts contributed to the antiviral effects. Tannins are known to have some antiviral properties, but the study showed that the isolated tannins had little to no effect on the pseudovirus, confirming that MoMo30 itself was responsible for the observed antiviral activity.
 
MoMo30’s Interaction with Different Spike Variants
The researchers conducted multiple enzyme-linked immunosorbent assays (ELISAs) to explore how MoMo30 interacts with different variants of the SARS-CoV-2 spike protein. These assays revealed that MoMo30 binds to the spike proteins of all the tested variants, with a slight preference for the Alpha variant. This broad-spectrum activity suggests that MoMo30 could be effective against various strains of the virus, including those that have mutated to evade other treatments.
 
Hypotheses on MoMo30’s Mechanism of Action
The researchers proposed three possible mechanisms by which MoMo30 inhibits viral entry:
 
-S1 Conformation Inhibition: MoMo30 may prevent the spike protein from adopting the necessary “up” conformation that allows it to bind to the ACE2 receptor. By inhibiting this conformational change, MoMo30 could block the virus from attaching to human cells.
 
-S2 Conformation Inhibition: After the virus binds to the receptor, the S2 subunit of the spike protein must undergo a conformational change to facilitate membrane fusion. MoMo30 may bind to the S2 domain, preventing this change and thus blocking viral entry.
 
-Protease Inhibition: Viral entry also depends on the cleavage of the spike protein by host cell proteases, such as TMPRSS2. MoMo30 may inhibit this proteolytic cleavage, preventing the virus from fusing with the cell membrane.
 
Conclusion and Future Implications
The findings from this study offer exciting possibilities for the development of new COVID-19 therapies. MoMo30’s ability to block viral fusion, combined with its broad-spectrum activity against multiple variants, makes it a promising candidate for further research and clinical development. While much remains to be learned about the precise mechanisms of MoMo30, its potential as a fusion inhibitor opens up new avenues for antiviral drug development.
 
The study findings were published in the peer-reviewed journal: Viruses.
https://www.mdpi.com/1999-4915/16/9/1433
 
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