Drug that destroys coronavirus in cats could destroy Covid-19 in humans

A new study published in the journal Nature Communications suggested that prodrug GC376 which is used to treat coronavirus disease in feline can be effective against the widespread novel coronavirus.

Prodrugs are compounds that have to be metabolized inside the body before they become active. GC376 gets converted to GC373.

A group of researchers at the University of Alberta, Canada, noted in the study that the prodrug targets an enzyme called Mpro in the SARS-CoV-2 and is a strong drug candidate for the treatment of coronavirus disease since it is already shown to be effective in animals.

The research team is set to launch phase 1 clinical trials of the drug soon.

Feline coronavirus

Feline coronavirus FCoV is a common infection that infects around 25 to 40 per cent of domestic cats in the world.

The virus enters a cat’s body through the oral route (licking, for example) and multiplies in the intestines. The cat will expel the virus in its feces where the virus may survive for up to a few weeks. Disinfectants can quickly destroy the FCoV.

According to the study, most cats that get this infection are asymptomatic. However, they may develop a mild form of diarrhea or it could lead to a life-threatening condition called feline infectious peritonitis (FIP).

The latter only develops when the FCoV virus develops a mutant strain inside the intestinal tract of the cat that can infect macrophages (a type of immune system cell) and spread throughout the body.

Prodrug GC376

Mpro is a protease present in the SARS-CoV-2 virus that helps the virus replicate and make copies of itself.

Prodrug GC376 has been proposed to have broad specificity against the Mpro of the novel coronavirus previously. To study the effect of this drug against the SARS-CoV-2 virus, the researchers exposed the virus to the drug in cell cultures.

It was found that GC376 when incubated with SARS-CoV-2 converts to GC373, which binds to the active site of Mpro protease, inhibiting the function of the protease. The active site of an enzyme is a pocket in the enzyme wherein the substrate (the compound an enzyme acts on) binds to it.

“We determined the three-dimensional shape of the protease with the drug in the active site pocket, showing the mechanism of inhibition. This will allow us to develop even more effective drugs," said Joanne Lemieux, the corresponding author of the study and a professor of biochemistry at the University of Alberta, Canada, as per the news release by the university.

Coronavirus treatments: what drugs might work against COVID-19?

As the COVID-19 pandemic continues to spread across the world, killing thousands and bringing economies to their knees, doctors, scientists and governments are on the lookout for safe and effective treatments to help those who are sick. And yet a large issue with COVID-19 is that there is, as yet, no cure.

Though there are treatments that can alleviate the symptoms – such as difficulty breathing – they do not address the underlying cause: the virus. The idea is that treating the symptoms will help prolong a patient’s life and buy time for their own immune systems to kick in and remove the infection.

While research into related coronaviruses over the last few decades has brought some promising looking drugs, only large clinical trials on patients with COVID-19 will be able to reveal precisely whether these interventions are safe and effective. Unfortunately, these kinds of large trials take time to carry out, but they are ongoing.

The World Heath Organization (WHO) announced it has helped to launch four “mega trials” against COVID-19 and there are countless more smaller ones coordinated in countries worldwide.

The WHO-backed trials are focusing on drugs that are thought to directly block SARS-CoV-2 – the virus strain that causes coronavirus COVID-19 – from replicating inside our lungs. Below are some of the main drugs these trials are looking at.

Remdesivir
This is an intravenous antiviral drug that was developed to block infection with related coronaviruses and even Ebola, and is one of the drugs the WHO is helping to investigate.

Remdisivir has already been shown to work against SARS-CoV-2 in cells in a dish in a lab as well as in mice infected with the virus. Remdesivir specifically targets key viral proteins involved in making new copies of the virus and prevents them from working.

Remdesivir has already been used in some COVID-19 patients in the US and appears safe, but large trials are needed to really know if this is the case.

This is a drug combination used against viruses like HIV. It works in a similar way to remdesivir by blocking key viral proteins called “proteases”.

Lopinavir/ritonavir has also been shown to be effective against SARS-CoV-2 in lab cells as well as in mice and is being tested alongside an antiviral drug called interferon beta. This is currently used to treat Multiple sclerosis and can enhance the natural defences of the body’s cells against COVID-19.
Chloroquine and hydroxychloroquine

Both of these drugs are currently used to treat malaria and the autoimmune disease lupus. 

Chloroquine has been tested against lots of different infections because in the lab it can block viruses – including SARS-CoV-2 - from getting inside cells placed in a dish and so prevent infection.

Outside the lab, chloroquine has not been demonstrated to have a profound effect at preventing disease and there is limited evidence so far that it can work for COVID-19, despite receiving a lot of hype from President Donald Trump. But again, large trials are needed and the WHO is supporting these.

Caution should be observed with chloroquine as it can have significant side effects in certain people and may even block the immune response – the desired result in lupus treatment.
Two other options

The above potential treatments all work by blocking some key element of the virus infection machinery using small molecules. Two other kinds of treatments are also being explored in trials that work in a different way.

The first is passive immunisation which is the transfer – or transfusion – of potential protective antibodies from someone who has been infected and recovered from COVID-19 to someone who is at high-risk or is suffering from a SARS-CoV-2 infection.

This so-called “convalescent sera” (which is a purified blood product from someone who has recovered from COVID-19) can block SARS-CoV-2 in cells in a dish in the lab and has the potential to help develop treatments. Passive immunisation for COVID-19 is being tested in trials across the world and so far results seem to suggest it is safe to use.

Another kind of possible treatment works by blocking parts of our own immune system that are likely overreacting to SARS-CoV-2 infection and contributing to the damage in our lungs.

In the limited studies that have been conducted on COVID-19, it seems that in some severe cases our immune response goes into overdrive without being able to clear the infection and this can increase the severity of the disease. When this happens, high levels of inflammation is found in the lungs.

Potential treatments that look at blocking the immune components linked to this severity have begun. That said, extreme caution must be taken when manipulating the immune response during an infection as in the absence of other therapies we rely on our immune response to limit the virus replicating.

So although specific treatments for COVID-19 are not yet available, drugs are being tested and clinical trials and starting to yield results. This, combined with the further knowledge that scientists are gaining about SARS-CoV-2 will help massively until a vaccine becomes available.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     

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Oral capsule designed to deliver insulin that usually has to be injected

Scientists in the United States have designed an oral drug capsule that can carry insulin and protect it from the harsh environment in the digestive tracts.

The study published  has shown that the capsule containing proteins that cannot be taken orally reaches the small intestine before breaking down to release dissolvable tiny needles.

Those needles then attach to the intestinal wall and release drug for fast uptake into the bloodstream, according to the study.

In tests in pigs, researchers from Massachusetts Institute of Technology (MIT) showed that this capsule could load a comparable amount of insulin to that of an injection.

Earlier this year, they developed a blueberry-sized capsule containing a small needle made of compressed insulin. Upon reaching the stomach, the needle injects the drug into the stomach lining. In the new study, the researchers developed a capsule that could inject its contents into the wall of the small intestine.

They coated the 30-millimeter-long capsule with a polymer that can survive the acidic environment of the stomach. The capsule breaks open in the small intestine as the pH is higher, and then springs three folded arms containing patches of one-millimeter-long needles that can carry insulin, according to the study.

When the arms unfold open, the force of their release allows the needles to just penetrate the topmost layer of the small intestine tissue. After insertion, the needles dissolve and release the drug.

Also, the arms would break apart after the needle patches are applied to reduce the risk of blockage in the intestine.

"We can deliver insulin, but we see applications for many other therapeutics and possibly vaccines," said the researcher.

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This Diabetes Drug Could Treat Heart Disease

Researchers have discovered that metformin -- a drug commonly used to treat Type-2 diabetes -- might also be used to treat a specific form of heart failure known as preserved ejection fraction (HFpEF), finds a new study.

In a mice study, researchers showed that metformin relaxes a key heart muscle protein called titin, allowing the heart to properly fill with blood before pumping it around the body. This improves the animals' capacity for exercise.

"We therefore conclude that metformin is a potential therapy for patients with HFpEF," said one of the researchers.

"Because the drug is already approved and well tolerated in humans, using it to target titin stiffness presents a unique opportunity for immediate translation to the clinic," said the Prof.

HFpEF is more common in women and other risk factors include hypertension, old age, and obesity.

Unlike other forms of heart failure, however, there are currently no drugs available to treat HFpEF, according to the researchers.



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New Drug Offers Hope for Bone Marrow Cancer Patients

A therapeutic drug has been found to improve outcomes and survival rates for patients with a serious type of bone marrow cancer.

In a clinical trial by researchers, patients with newly diagnosed myeloma were treated with a drug called lenalidomide.

The results showed an improvement for those who received lenalidomide drug, compared to those not receiving it.

This is a major breakthrough as it shows that the long-term use of lenalidomide significantly improves the time myeloma patients stay in remission after initial therapy. 

Myeloma is a cancer of the plasma cells and it can affect several areas of the body, such as the spine, skull, pelvis and ribs. Current treatment usually involves chemotherapy and a stem-cell transplant.

It is a huge step and, importantly, identifies that for younger patients lenalidomide improves their overall survival for this difficult-to-treat bone marrow cancer. Our research highlights that lenalidomide should be considered for newly diagnosed patients following stem-cell transplantation. 

As part of the study, a total of 1,137 newly diagnosed patients were randomly assigned to lenalidomide maintenance therapy and 834 patients to observation - this was after they completed their initial treatment.

The results show that lenalidomide can prolong the average remission time by more than two years in younger patients and by well over a year in older, less fit patients.

It reduced the risk of progression or death by more than 50 per cent in both groups.

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Anti-anxiety drug can reverse brain deficits caused by alcohol

Researchers have identified an anti-anxiety drug that could potentially reverse the damage caused to the brain by alcohol abuse. 

Alcohol abuse and addiction is characterised by extended periods of heavy alcohol use, binges and abstinence, and anxiety and depression which contribute to relapse.

The findings showed that tandospirone can help our brains reboot and reverse the damage on the regeneration of brain cells, caused by heavy alcohol consumption.

"Tandospirone drug is available only in China and Japan. It is commonly used there and shown to be highly effective in treating general anxiety and well tolerated with limited adverse effects," saida researcher.

In the study, adult mice who underwent two weeks of daily treatment with the drug tandospirone saw a reduction in anxiety-like behaviours associated with alcohol withdrawal.

Tandospirone reversed the effects of 15 weeks of binge-like alcohol consumption on neurogenesis -- the ability of the brain to grow and replace neurons (brain cells).

This was also accompanied by a significant decrease in binge-like alcohol intake.

"This is a novel discovery that tandospirone can reverse the deficit in neurogenesis caused by alcohol," said the lead author of the study.

The study also opens the way to look at if neurogenesis is associated with other substance-abuse deficits, such as in memory and learning, and whether this compound can reverse these.

"Tandospirone is not just another drug that shows promise in helping to reduce binge drinking," the researcher said.

"While it could possibly have that effect, it might be able to help reboot the brain and reverse the deficits the alcohol abuse causes - both the inhibition to the brain's ability to regenerate, and the behavioural consequences that come from what alcohol is doing to the brain, like increases in anxiety and depression," she noted.

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