One study found a supplement that stopped the SARS-COV-2 virus from entering the brain, damaging cerebral vessels, and protecting against long-COVID.
Researchers at the University de Paris-Grans, the University of Lille in France, the University of L লbeck in Germany and DZHK (German Research Center for Cardiovascular Research) have discovered that melatonin-based drugs such as agomelatine and rameltion, as well as slowly-melatonin S -2 may prevent entry and prevent damage to cerebral vessels in a new study.
According to the results, melatonin may be effective in the treatment of Long Covid because it relieves some of the neurological symptoms or disorders associated with Long Covid or PASC (post-acute sequelae of COVID-19).
COVID-19 is a complex disease with short and long term respiratory, inflammatory and neurological symptoms caused by SARS-CoV-2 virus.
Human SARS-Cov-2 brain attacks have been documented, and are thought to be associated with Long COVID or PASC conditions.
The K18-hACE2 animal model of COVID-19 contains particularly severe brain infections.
Researchers have discovered that drugs marketed with melatonin and two melatonins, agomelatine and rameltion, K18-hACE2 inhibit SARS-CoV-2 given to rats to enter the brain, reduce virus-induced damage to small cerebral arteries, and immune cells. Inflammation
The allosteric human angiotensin-converting enzyme 2 (ACE2) of melatonin, which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2, prevents SARS-CoV-2 from entering the brain through endothelial cells.
The results of the study bring new possibilities for reuse of melatonergic drugs to prevent SARS-CoV-2 brain infections and COVID-19-related chronic neurological disorders.
The results of the study were posted on a preprint server and are currently under peer review.
To date, the SARS-CoV-2 coronavirus has infected more than 499.2 million people worldwide and more than 6.20 million people have died from COVID-19.
It is now thought that up to 35% of all people infected with the SARS-CoV-2 coronavirus, without symptoms or showing mild, moderate or severe symptoms at the time of infection, will continue to suffer from a variety of long-term problems. Diseases known as medical and health concerns or Long Covid.
Nervous disorders such as headache, nausea, anosmia, myalgia, cognitive impairment, cerebral palsy, dementia, bleeding, syncope, convulsions and stroke are among the most common symptoms of long covid.
The SARS-CoV-2 coronavirus has now been shown to be capable of infecting the human brain and causing a variety of problems, according to research.
Melatonin is a natural hormone produced by the pineal gland at night that has a variety of effects on the central nervous system (CNS), including the regulation of the biological master clock in the hypothalamus and sleep induction.
Melatonin also has anti-inflammatory, anti-oxidant and neuroprotective effects.
Melatonin acts on several target proteins, the most well-known being the two high-affinity G protein-coupled receptors, MT1 and MT2.
Melatonin-based drugs that act on MT1 and MT2 receptors, such as rameltion, agomelatine, tacimelatine, and slow-release melatonin, are being used to treat insomnia, ‘jet lag’, and depression, and have been shown to have some favorable effects. Profile with.
Recent system-network-pharmacology studies have identified melatonin as one of the top-scoring molecules with potential anti-COVID-19 activity.
Several review studies have estimated the potential positive effects of melatonin in the treatment of Covid-19 based on its broader activity.
It should be highlighted, however, that currently there is very little experimental data from animal models or humans.
The same research team recently demonstrated that treating K18-hACE2 rats (revealing human ACE2 receptors) with melatonin dampens virus-induced type I and type III interferon production in the lungs, leading to serious clinical outcomes and improved survival.
This study demonstrated that melatonin and melatonin-like compounds in K18-hACE2 COVID-19 can reduce SARS-CoV-2 transmission to the brain in animal models that have high levels of virus penetration, reducing viral penetration through small endothelial cells in the brain. It is accompanied by a decrease in neuroinflammatory markers as well as symptoms of immune cell infiltration.
In addition, the research team found a new target for melatonin. Melatonin binds to ACE2 to stop SARS-CoV-2 from entering brain cells, which are receptors for SARS-CoV-2 in brain cells.
To evaluate the potential positive effects of melatonin on SARS-CoV-2 infections in the brain and the potential positive effects of two clinically available melatonin receptors, ligand agomelatine (AgoMLT) and ramelteon (RML), the research team used a K18-hACE2 rat model, the KARS. -CoV-2 brain infection.
Since melatonin has a short plasma half-life of 20-30 minutes, two doses have been chosen: 10 mg / kg (MLT10) and 50 mg / kg (MLT50), with the aim of maintaining high levels throughout. Intra-peritoneal treatment of rats with the substance was started two days before intranasal infection and was repeated daily for seven days after infection (DPI 7) until rat sacrifice. Biochemical and histological analysis was performed on the lungs and brain.
According to the results of the study, the drug melatonin improves the clinical score and also reduces the viral load on the participants’ brains.
While microscopy of brain fragments revealed lower expression of N-protein in treated animals, the change in the severely infected hypothalamus area of the brain is significantly more pronounced.
The results of this work show that melatonin administration reduces SARS-CoV-2 brain infections, even in the K18-hACE2 mouse model, which is highly susceptible to brain infections.
Melatonin reduces inflammation of the brain and prevents virus-induced damage to cerebral arteries, according to the results.
Studies have also shown that melatonin and its derivatives can protect the brain from infection by targeting vascular endothelial cells in the body’s blood vessels.
The results show that endothelial cells in the brain are potentially receptor-mediated melatonin target cells, and that melatonin reduces the expression of endogenous ACE2 and NFB pathway genes in these cells, potentially immune to melatonin in cerebral small arteries. K18-hACE2 is not responsible for the downregulation of mouse Ace2, which is dependent on human ACE2 produced under the control of the K18 promoter, which is not regulated by melatonin, suggesting that melatonin has another inhibitory mechanism.
The results show that melatonin binds to an allosteric binding site at ACE2. This changes the position of the helix ACE2 19-52 which interacts with RBD, which affects the entry of viral cells.
There is strong evidence that melatonin can prevent SARS-CoV-2 coronavirus from infecting the brain and also prevent long-term COVID-19 problems from brain problems or damage caused by the virus.
It is also worth noting that previous studies have shown that melatonin has great potential as a preventive and therapeutic agent, an observational study found that its use was associated with a 52 percent lower risk of a positive SARS-CoV-2 PCR test among African Americans. .
It was also discovered that the combination of melatonin with fluvoxamine (fluvoxamine helps increase plasma melatonin levels) reduced the need for hospitalization of Covid-19 patients who were high-risk ambulators.
Consequently, these recent findings, combined with previous studies, point to the therapeutic potential of melatonin in COVID-19.
It has been speculated that long-term neurological disorders related to long covid can be avoided by using melatonin to reduce brain infections and central inflammatory response (CIR).
Preliminary results of ongoing studies, which will be published soon, indicate that melatonin is effective in preventing SARS-CoV-2 infection and viral persistence when combined with the Omicron variant.
Melatonin is a supplement that can be purchased over-the-counter. Used properly, it has a low profile and low risk profile. We do not support readers to self-determine and start taking melatonin without first consulting a licensed physician.
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