Nikhil Prasad Fact checked by:Thailand Medical News Team Dec 10, 2024 1 day, 21 hours, 42 minutes ago
Medical News: A breakthrough study has revealed the crucial role of glutamine metabolism in the replication of coronaviruses. This groundbreaking research was conducted by experts from Cornell University’s Department of Molecular Medicine and Microbiology-USA. Their findings could pave the way for a new class of antiviral drugs that target this essential metabolic process.
Cornell Study Finds That Glutamine Metabolism is Key to Coronavirus Survival
Glutamine is an amino acid that plays a critical role in cell growth and energy production. It turns out that coronaviruses, including SARS-CoV-2 (responsible for COVID-19) and other human coronaviruses like HCoV-OC43, hijack this metabolic pathway to fuel their replication. This
Medical News report explores how the study has uncovered this dependency and its potential implications for future treatments.
How Viruses Hijack Host Metabolism
Viruses cannot reproduce on their own - they need host cells. To replicate efficiently, they reprogram the host’s metabolic machinery. The study found that coronaviruses cause a surge in the activity of glutaminase enzymes, which convert glutamine into glutamate, an essential building block for energy and biosynthesis. Researchers observed this phenomenon in different cell types infected by SARS-CoV-2, HCoV-OC43, and HCoV-229E.
One of the critical findings of this research was that when the glutaminase enzymes GLS and GLS2 were blocked using specialized inhibitors, viral replication was significantly reduced. These inhibitors, SU1 and UP4, showed promising results both in cell cultures and in a mouse model of SARS-CoV-2 infection.
Testing the New Drugs
The study employed advanced techniques such as targeted metabolomics and genetic silencing of glutaminase enzymes to demonstrate the relationship between glutamine metabolism and viral replication. Notably, the allosteric inhibitors SU1 and UP4 showed distinct effectiveness. SU1, which targets both GLS and GLS2, was more effective than UP4, which is selective for GLS.
In laboratory experiments, these inhibitors not only reduced the amount of viral RNA in infected cells but also significantly extended the survival of mice infected with SARS-CoV-2. Treated mice survived beyond 19 days, while untreated controls succumbed to the infection within 10 days. This dramatic difference underscores the potential of these inhibitors as antiviral agents.
A Promising Mechanism of Action
The study explains how these inhibitors work at a molecular level. SU1 and UP4 stabilize the inactive forms of glutaminase enzymes, preventing them from carrying out their metabolic functions. Without glutamine metabolism, viruses lack the resources to replicate efficiently. Furthermore, the treatment reduced virus-induced changes in the host cell’s metabolic profile, effectively reversing the metabolic hijacking.
Broader Implications
The implications of this discovery
extend beyond coronaviruses. Glutamine metabolism is a common target for many types of viruses. This raises the possibility of developing broad-spectrum antiviral drugs based on the same principle. Additionally, since glutaminase inhibitors are already being explored for cancer treatments, they have a safety profile that could expedite their development for antiviral use.
Study Limitations and Future Directions
While the findings are exciting, there are still questions to answer. For example, different cell types and virus strains showed varying dependencies on GLS versus GLS2. Understanding these differences will help refine the use of these inhibitors for specific infections. Moreover, researchers aim to explore whether other viruses share this dependency and whether glutaminase inhibitors can be tailored further for better absorption and efficacy.
Conclusion
This study underscores the importance of targeting host metabolic pathways as a novel strategy for antiviral therapy. By disrupting glutamine metabolism, researchers were able to block coronavirus replication effectively in cells and in animal models. This finding could lead to a new class of drugs that not only tackle SARS-CoV-2 but also other coronaviruses and potentially a wide range of viral infections.
The conclusions highlight the urgent need for continued research into metabolic inhibitors. These drugs hold promise as safe, effective treatments with the potential to mitigate future pandemics. The study serves as a reminder of the intricate interplay between viruses and host biology and how scientific innovation can turn the tide in the fight against infectious diseases.
The study findings were published in the peer-reviewed Journal of Biological Chemistry.
https://www.sciencedirect.com/science/article/pii/S0021925824025651
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Read Also:
https://www.thailandmedical.news/news/covid-19-news-the-role-of-glutamine-deficiency-in-immune-and-endothelial-cell-dysfunction-in-covid-19-and-potential-therapeutic-strategies
https://www.thailandmedical.news/news/breaking-wuhan-study-shows-that-glutamine-and-pyruvate-supplementation,-also-rosiglitazone-can-reduce-and-prevent-hyperinflammation-in-covid-19
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