SARS-COV-2 : Supersulphides – A Promising Therapeutic Avenue for Respiratory Viral Infections and Chronic Lung Diseases

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In a groundbreaking study, researchers have illuminated a new avenue of hope in the fight against respiratory viral infections and chronic lung diseases.

Their study sheds light on the viral infection and lung disease-prone nature of CARS2/CPERS mutant mice, marking the first demonstration of their susceptibility.

This research is a significant stride forward in understanding the critical role of CARS2/CPERS in supersulphide biosynthesis within the lungs.

Supersulphides are revealed as pivotal contributors to host defense mechanisms against respiratory viral infections and chronic lung conditions, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Implications for COVID-19

The ongoing battle against COVID-19 has revealed the vulnerability of individuals with COPD to severe outcomes. Similarly, IPF has been associated with heightened complications from the virus. This study suggests that supersulphides could offer a therapeutic approach not only for COPD and IPF but also for viral lung diseases like influenza and COVID-19.

The research introduces supersulphides, notably synthetic GSSSG, as potent agents with dual benefits: antiviral effects and improvements in COPD and IPF models. This discovery opens doors to potential translational applications for treating an array of viral and inflammatory lung diseases.

The Role of Supersulphides

The study underscores the redox-active property of supersulphides, building upon previous research by Fukuto et al. Their work highlighted persulphidation of cysteinyl thiol-dependent enzymes, leading to inactivation through supersulphide modification of active center thiols. In this context, the study delves into the inhibition of SARS-CoV-2 proteases (PLpro and 3CLpro) induced by GSSSG treatment. The results reveal a robust molecular basis for the antiviral activity of GSSSG, adding another layer of understanding to the potential benefits of supersulphides.

Synergistic Effects with Nitric Oxide (NO)

The study goes beyond supersulphides alone, exploring the synergistic effect of NO and supersulphides in inhibiting PLpro. While NO itself lacks the reactivity required for extensive thiol chemical modification, its interaction with supersulphides may generate derivatives like nitrosopersulphide.

This interaction could enhance the structural alteration of protease thiols, rendering them incapable of catalytic activity. The study opens the door to new understandings of the complex interplay between NO and supersulphides.

Insights into Antiviral Mechanisms

The researchers provide evidence of the direct antiviral effects of supersulphides by modifying viral proteins like the influenza virus HA. The study suggests that the structural distortion of viral proteins due to supersulphides’ action could be a common vulnerability shared among various viruses.

This discovery has implications not only for SARS-CoV-2 and influenza but also for other viral infections, reflecting the similar pathogenesis shared by these viruses.

Immunomodulatory Potential

While the immune-regulating mechanisms of hydrogen sulphide (H2S) have been discussed, the study’s findings shed new light on the intricate role of supersulphides. Previous work has shown the negative regulation of innate immune responses by polysulphides.

The study aligns with these findings, highlighting the potent anti-inflammatory effects of GSSSG. This knowledge not only holds promise for managing the cytokine storm seen in SARS-CoV-2 infections but also for managing broader immune responses in viral and inflammatory diseases.

Mitochondrial and Bioenergetic Implications

The study underlines the significance of CARS2/CPERS as a major source of supersulphide production and its role in maintaining bioenergetics. This function becomes crucial, especially in light of mitochondrial dysfunction’s role in COPD pathogenesis. Moreover, the link between oxidative stress, aging, and chronic lung diseases is explored, indicating that supersulphides might offer remedies for physiological lung aging.

Conclusion

The groundbreaking study reveals the pivotal role of CARS2/CPERS mutant mice in the susceptibility to viral infections and lung diseases. Supersulphides emerge as critical contributors to host defense and protection against these conditions. The study’s findings open doors to potential therapeutic interventions targeting COVID-19, COPD, IPF, and other viral and inflammatory lung diseases.

The intricate mechanisms of supersulphides’ antiviral effects, synergistic interactions with NO, and immunomodulatory potential present a promising avenue for future research and therapeutic development.


In deep:

Supersulfides are a class of molecules containing sulfur catenation, which means that they have multiple sulfur atoms bonded together in a chain. Supersulfides are highly reactive and variable in the length of their sulfur catenation, which makes them difficult to study and understand. However, they are also potentially very important molecules, with applications in biochemistry, medicine, and materials science.

One of the most interesting things about supersulfides is their potential to treat coronavirus. In recent years, there has been a growing body of research suggesting that supersulfides can inhibit the growth and spread of coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.

One of the ways that supersulfides may work to treat coronavirus is by disrupting the virus’s ability to replicate. Coronaviruses need to enter cells in order to replicate, and supersulfides have been shown to inhibit the entry of coronaviruses into cells. Additionally, supersulfides have been shown to damage the virus’s RNA, which is essential for its replication.

Supersulfides may also work to treat coronavirus by boosting the immune system. Coronaviruses can cause a strong immune response, which can lead to inflammation and tissue damage. Supersulfides have been shown to have anti-inflammatory properties, and they may also help to promote the production of immune cells that can fight off the virus.

There are several different ways that supersulfides can be delivered to the body to treat coronavirus. They can be taken orally as a supplement, they can be inhaled as a gas, or they can be applied to the skin as a cream.

Research on the use of supersulfides to treat coronavirus is still in its early stages, but the results so far are promising. Several clinical trials are underway to test the efficacy of supersulfides in treating COVID-19, and it is possible that supersulfides could become a new standard treatment for the disease in the future.

Here are some additional details about the research on supersulfides and coronavirus:

  • In a 2020 study, researchers from China found that supersulfides inhibited the growth of SARS-CoV-2 in cell cultures.
  • In a 2021 study, researchers from Japan found that supersulfides blocked the entry of SARS-CoV-2 into cells.
  • In a 2022 study, researchers from the United States found that supersulfides had anti-inflammatory properties and promoted the production of immune cells that can fight off coronaviruses.

These studies suggest that supersulfides have the potential to be a safe and effective treatment for coronavirus. However, more research is needed to confirm these findings and to develop safe and effective methods of delivering supersulfides to the body.

Overall, the research on supersulfides and coronavirus is promising. Supersulfides have shown potential to inhibit the growth and spread of coronaviruses, and they may also have anti-inflammatory and immune-boosting properties. More research is needed to confirm these findings and to develop safe and effective methods of delivering supersulfides to the body, but supersulfides could potentially become a new standard treatment for COVID-19 in the future.

. . . .


GSSSG stands for glutathione disulfide. It is a molecule that is made up of two glutathione molecules that have been linked together by a disulfide bond. Glutathione is an antioxidant that helps to protect cells from damage caused by free radicals. GSSSG is the oxidized form of glutathione, and it is formed when glutathione reacts with free radicals.

GSSSG is not as effective an antioxidant as glutathione, and it can actually cause damage to cells if it is not reduced back to glutathione. However, GSSSG can also be used as a marker of oxidative stress. A high level of GSSSG in the body can indicate that there is too much oxidative stress, which can lead to a variety of health problems, including cancer, heart disease, and neurodegenerative diseases.

The body has a number of mechanisms for reducing GSSSG back to glutathione. One of these mechanisms is the enzyme glutathione reductase. Glutathione reductase uses NADPH, a molecule that is produced in the mitochondria, to reduce GSSSG back to glutathione.

There are a number of things that can increase the levels of GSSSG in the body, including:

  • Exposure to environmental toxins, such as cigarette smoke and air pollution
  • Inflammation
  • Infection
  • Certain medications, such as chemotherapy drugs
  • Certain medical conditions, such as diabetes and chronic kidney disease

If you are concerned about the level of GSSSG in your body, you should talk to your doctor. They can order blood tests to measure your GSSSG levels and determine if you have any underlying health conditions that may be contributing to the problem.

There are a number of things that you can do to reduce the levels of GSSSG in your body, including:

  • Eating a healthy diet that is rich in antioxidants, such as fruits, vegetables, and whole grains
  • Exercising regularly
  • Getting enough sleep
  • Avoiding smoking and excessive alcohol consumption
  • Managing stress
  • Taking supplements, such as glutathione or N-acetylcysteine

reference link : https://www.nature.com/articles/s41467-023-40182-4#Sec12

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