Nitric Oxide’s Potential Against COVID-19 Explored

Medical News: Nitric oxide (NO), a naturally occurring gas in the body, is showing promise in reducing the infectious capabilities of the SARS-CoV-2 virus, the agent behind COVID-19. Recent research involving Spanish biomedical researchers aims to uncover how NO may inhibit the virus’s ability to bind to human cells, thereby lowering infection rates.


Nitric Oxide’s Potential Against COVID-19 Explored

A Promising Molecule in the Fight Against COVID-19
Since the onset of the COVID-19 pandemic, scientists have sought ways to stop the virus from binding to human cells. The COVID-19 virus uses a protein called ACE2 to enter cells, and any interference with this binding process can potentially reduce infections. This Medical News report presents recent findings on how Nitric oxide might help limit the virus’s binding ability.

Researchers from several Spanish institutions - Instituto de Investigaciones Biomédicas Sols-Morreale (Madrid), Universidad de Las Palmas de Gran Canaria, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, and Universidad Complutense de Madrid - conducted an in-depth study on how Nitric oxide affects ACE2 and viral interaction. Their research suggests that NO and NO-donating compounds might interfere with the virus’s binding capabilities to human cells, specifically targeting its spike protein.
 
How Nitric Oxide Could Help
Nitric oxide is a gas that the body naturally produces and is known for its role in expanding blood vessels and enhancing immune responses. Because of its complex role in the body, Nitric oxide has been studied for therapeutic use in various diseases, including respiratory distress and pulmonary hypertension. The current study explores how Nitric oxide might work in two main ways to prevent COVID-19 infection:
 
-Blocking the Viral Spike Protein: The COVID-19 virus uses its spike protein to bind to ACE2, allowing it to enter human cells. The researchers experimented with NO donors (substances that release Nitric oxide over time), finding that Nitric oxide interferes with this spike-ACE2 interaction. They showed that certain Nitric oxide donors could effectively block this binding in laboratory settings, thus potentially reducing the virus’s ability to infect cells.
 
-Reducing ACE2 Activity: Besides blocking the virus’s binding capability, NO was also observed to reduce ACE2 activity. The ACE2 enzyme itself plays a role in regulating blood pressure and inflammation, and excessive activation can lead to complications. By dampening ACE2 activity, Nitric oxide might help mitigate the overactive immune responses often seen in severe COVID-19 cases.
 
These findings could be significant, particularly as the virus has mutated and produced several variants. The study found that Nitric oxide maintained its efficacy in blocking both the Alpha and Gamma variants of the virus. These results are encouraging, as they suggest that Nitric oxide’s effec ts might be stable across different strains, although further studies are needed to confirm this.
 
Key Findings from the Study
The researchers employed two types of NO donors: DETA-NONOate (a slow-releasing NO donor) and S-nitrosoglutathione (GSNO) (a fast-releasing NO donor). Experiments showed that both donors significantly reduced ACE2 enzyme activity and blocked the spike protein’s binding to ACE2. Here’s a closer look at some specific findings:
 
- Nitric oxide and ACE2 Inhibition: The study showed that NO directly inhibits ACE2, potentially reducing COVID-19’s infectivity. ACE2 inhibition was achieved using both DETA-NONOate and GSNO, with GSNO showing more rapid and intense inhibition due to its quick-release properties.
 
-Blocking Spike Protein Binding: Tests were conducted using human liver cells (HepG2) and lung cells (A549) engineered to express ACE2, representing potential viral entry points. When treated with NO donors, both cell types displayed reduced binding affinity to the virus’s spike protein, lowering infection rates in these laboratory settings.
 
-Stable Effect Across Variants: The study focused on the Alpha and Gamma spike variants, two strains known for their infectivity. Interestingly, the blocking effect of Nitric oxide on ACE2 binding was consistent across both, showing promise for NO’s application even as the virus evolves.
 
-Reduced Cell Damage: Importantly, Nitric oxide treatment did not adversely affect the viability of human cells, suggesting its potential as a safer therapeutic option. Furthermore, murine macrophages (immune cells from mice) were stimulated to release Nitric oxide, which also successfully blocked viral binding in a controlled setting.
 
Practical Implications and Future Research
While Nitric oxide is already in therapeutic use for various lung and cardiovascular conditions, this study provides a new perspective on its potential application against COVID-19. These findings might inform future treatments, particularly in vulnerable populations who face severe disease risks.
 
Current antiviral options, including drugs like remdesivir and antibody treatments, often require specific conditions and have variable effectiveness. Nitric oxide might offer an alternative or complementary approach, particularly in cases where virus mutations challenge current treatments. Moreover, Nitric oxide’s dual function in blocking viral entry and reducing ACE2 activity provides a unique advantage in managing both the viral and inflammatory aspects of COVID-19.
 
Researchers are also examining Nitric oxide’s safety profile and the best delivery methods, such as inhalation, for broader application. The development of slow-release Nitric oxide donors or other innovative delivery mechanisms could enhance its efficacy in clinical settings.
 
Conclusions
This study emphasizes the potential role of Nitric oxide in combating COVID-19, particularly by blocking the virus’s entry into cells and limiting excessive ACE2 activity. By reducing viral infectivity and possibly tempering the body’s inflammatory response, Nitric oxide could be a valuable addition to COVID-19 treatment options. Its unique antiviral and immune-regulatory properties align well with the multifaceted challenges posed by COVID-19.
 
The findings underscore the need for further research to explore Nitric oxide’s mechanism of action, safety in various populations, and adaptability across emerging COVID-19 variants. Future studies might also investigate its effects on other receptor-based viral infections, broadening its therapeutic scope.
 
The study findings were published in the peer-reviewed journal: Antioxidants.
https://www.mdpi.com/2076-3921/13/11/1301
 
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