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A supplement that doesn’t allow COVID to enter brain, damage cerebral vessels – study finds

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A study reveals a supplement that stops the SARS-COV-2 virus from entering the brain, damaging cerebral vessels and also protects against Long-COVID.

Researchers from the Université de Paris-Grance, the University of Lille in France, the University of Lübeck in Germany, and the DZHK (German Research Centre for Cardiovascular Research) have discovered that melatonin-based drugs like agomelatine and ramelteon, as well as slow-release melatonin supplements, can inhibit SARS-Cov-2 entry into the brain and prevent cerebral vessel damage in a new study.

Melatonin, according to the findings, may be effective in the treatment of Long COVID since it alleviates some of the neurological symptoms or disorders associated with Long COVID or PASC (Post-acute Sequelae of COVID-19).

COVID-19 is a complicated disease with short- and long-term respiratory, inflammatory, and neurological symptoms caused by the SARS-CoV-2 virus.

Human SARS-Cov-2 brain invasion has been documented, and it is thought to be involved in Long COVID or PASC conditions.

The K18-hACE2 animal model of COVID-19 has a particularly severe brain infection.

The researchers discovered that giving melatonin and two melatonin-derived marketed medications, agomelatine and ramelteon, to K18-hACE2 mice prevents SARS-CoV-2 from entering the brain, lowering virus-induced damage to small cerebral arteries, immune cell infiltration, and brain inflammation.

Melatonin’s allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with ACE2’s cell entry receptor function for SARS-CoV-2, prevents SARS-CoV-2 from entering the brain through endothelial cells, according to the research.

The findings of the study bring up new possibilities for repurposing melatonergic medications in the prevention of SARS-CoV-2 brain infection and COVID-19-related long-term neurological disorders.

The findings of the study were posted on a preprint server and are currently undergoing peer review.

To date, the SARS-CoV-2 coronavirus has infected over 499.2 million individuals worldwide and killed over 6.20 million people with COVID-19.

It is now thought that up to 35% of all persons who have been infected with the SARS-CoV-2 coronavirus, whether asymptomatic or exhibiting mild, moderate, or severe symptoms during infection, would continue to suffer from a variety of long-term medical and health concerns or diseases known as Long COVID.

Neurological disorders such as headache, nausea, anosmia, myalgia, cognitive issues, brain fogginess, dementia, hemorrhage, syncope, seizure, and stroke are among the most common signs of Long COVID.

SARS-CoV-2 coronavirus has now been proven to be capable of infecting the human brain and causing an array 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 the induction of sleep.

Melatonin also has anti-inflammatory, anti-oxidant, and neuroprotective effects.

Melatonin acts on a number of target proteins, the most well-known of which are the two high-affinity G protein-coupled receptors, MT1 and MT2.

Melatonin-based medicines that operate on MT1 and MT2 receptors, such as ramelteon, agomelatine, tasimelteon, and slow-release melatonin, are being used to treat insomnia, ‘jet lag,’ and depression, and have been shown to have a favorable safety profile with few or no adverse effects.

Melatonin was identified as one of the top-scoring molecules with potential anti-COVID-19 activity in recent systems-network-pharmacology studies.

Several review studies have speculated on melatonin’s potential positive effects in treating COVID-19 based on its broad spectrum of activity.

It should be highlighted, however, that there are currently very few experimental data from animal models or humans.

The same research team recently demonstrated that treating K18-hACE2 mice (expressing the human ACE2 receptor) with melatonin delayed the occurrence of severe clinical outcomes and enhanced survival, in part by dampening virus-induced type I and type III interferon production in the lungs.

This study proved that Melatonin and melatonin-like compounds can reduce SARS-CoV-2 infection of the brain in the K18-hACE2 COVID-19 animal model, which has a high level of virus penetration, by lowering viral entrance through brain endothelial cells and damage to cerebral small arteries. This is accompanied by a decrease in neuroinflammatory markers as well as signs of immune cell infiltration.

In addition, the study team found a new target for melatonin. Melatonin stops SARS-CoV-2 from getting into brain cells by binding to ACE2, which is the receptor for SARS-CoV-2 in brain cells.

To assess the possible positive effect of melatonin and the two clinically available melatonin receptor ligands agomelatine (AgoMLT) and ramelteon (RML) on SARS-CoV-2 infection in the brain, the research team used K18-hACE2 mice, a robust model of SARS-CoV-2 brain infection.

Because melatonin has a short plasma half-life of 20-30 minutes, two doses were chosen for it: 10 mg/kg (MLT10) and 50 mg/kg (MLT50), with the goal of keeping levels high throughout time. Intra-peritoneal treatment of mice with substances began two days before intranasal infection and was repeated daily until the mice were sacrificed at the latest on day seven following infection (DPI7). Biochemical and histological analyses were performed on the lungs and brain.

According to the findings of the study, melatonin medication improves the clinical score while also decreasing the viral load in the brain of the participants.

Microscopy of brain slices revealed lower expression of the N-protein in treated animals, with the change being considerably more obvious in the severely infected hypothalamus area of the brain.

The results of this work show that melatonin administration reduces SARS-CoV-2 brain infection, even in the K18-hACE2 mouse model, which is extremely sensitive to brain infection.

Melatonin also reduces brain inflammation and prevents virus-induced damage to cerebral tiny arteries, according to the findings.

The study also found that melatonin and its derivatives might protect the brain from infection by targeting vascular endothelia, which are cells in the body’s blood vessels.

The findings reveal that brain endothelial cells are possible receptor-mediated melatonin target cells, and that melatonin reduces the expression of endogenous ACE2 and NFB pathway genes in these cells, potentially contributing to melatonin’s protective effect on cerebral small arteries. Downregulation of mouse Ace2 does not account for the reduced virus entrance in K18-hACE2 mice, which is dependent on human ACE2 produced under the control of the K18 promoter, which is not downregulated by melatonin, implying that melatonin has another inhibitory mechanism.

The findings show that melatonin binds to an allosteric binding site at ACE2. It changes the position of the helix ACE2 19-52 that contacts RBD, which has an effect on viral cell entry.

There is strong evidence that melatonin can stop the SARS-CoV-2 coronavirus from infecting the brain and also stop the long-term COVID-19 problems that come from brain problems or damage caused by the virus.

It’s also worth noting that previous research has shown that melatonin has great potential as a preventative and therapeutic agent, with one observational study finding that its use was linked to a 52 percent lower risk of a positive SARS-CoV-2 PCR test in African Americans.

It was also discovered that combining melatonin with fluvoxamine (fluvoxamine helps boost plasma melatonin levels) reduced the requirement for hospitalization in COVID-19 patients who were high-risk ambulatory.

As a result, these recent results, combined with previous research, point to melatonin’s therapeutic potential in COVID-19.

It is hypothesized that long-term neurological diseases related to Long COVID could be avoided/attenuated by using melatonin to reduce brain infection and the central inflammatory response (CIR).

Preliminary findings from ongoing studies, which will be published soon, indicate that melatonin is effective in preventing SARS-CoV-2 infections and viral persistence when combined with the Omicron variant.

Melatonin is a supplement that can be purchased over-the-counter. When used correctly, it is inexpensive and has a low risk profile. We do not advocate that readers self-prescribe and begin taking melatonin without first consulting a licensed doctor.

Image Credit: Getty

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