Researchers discover a new monoclonal antibody that is effective against SARS-CoV-2 variants

A new monoclonal antibody targets a particular region of the receptor-binding domain (RBD) on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This region is usually not accessible to immune cells,  which may be why it has broad neutralizing capabilities.

With the coronavirus disease 2019 (COVID-19) pandemic continuing around the globe, new mutants of SARS-CoV-2 are emerging. These new variants are likely more infectious and can better evade our immune response.

The SARS-CoV-2 spike protein, in particular the RBD, is key in binding to host receptors, mainly the angiotensin-converting enzyme 2 (ACE2) in humans. One highly conserved region of the RBD, called antigenic site II, can elicit neutralizing antibodies. However, this region is generally inaccessible because of the RBD conformation, and there is a low fraction of antibodies targeting this site in infected individuals.

In a new study published in the bioRxiv* preprint server, researchers report a new monoclonal antibody that is targeted toward site II and has a broad neutralizing capability.

Testing potency of monoclonal antibody

The authors sorted spike protein-specific memory B cells from a convalescent individual 75 days after symptom onset. They found one monoclonal antibody, called S2X259, which reacted with 29 of 30 spike proteins of sarbecoviruses, including SARS-CoV-2 and its new variants. The antibody also reacted with bat sarbecoviruses, suggesting its broad neutralizing capability.

The antibody also bound strongly to 10 RBDs from different sarbecoviruses. The binding of this antibody was not affected by the different single-point RBD mutations seen in the new variants of SARS-CoV-2, including the United Kingdom, South African, Brazilian, and the B.1.427/B.1.429 variants.

Using pseudotyped virus systems, the team found that the antibody neutralized SARS-CoV-2 and did not lose its potency against the different variants or the N439K or Y453F mutation. The antibody not only neutralized a variety of sarbecoviruses that use the ACE2 receptor but also cross-reacts with sarbecoviruses that do not use ACE2 for infection.

To understand how this antibody has high neutralizing potency, the team imaged the complex formed between the spike protein and the antibody using cryo-electron microscopy. They found that the antibody recognizes a glycan-free site, which requires two RBDs to be in the open conformation. It forms contacts with residues 369-386, 404-411, and 499-508 in the RBD.

The epitope the antibody binds to is conserved in all the circulating SARS-CoV-2 variants. In addition, it does not target the 417 or 484 residues (mutations here are found in B.1.351 and P.1), and this could be why it is potent against the different variants.

The action of this antibody does not affect the neutralization effect of class 1 and class 3 antibodies. The majority of approved antibodies for clinical use belong to these classes. Hence, the new antibody can be used in combination with other antibodies to increase neutralization breadth.Potential use against a broad range of sarbecoviruses

Potential use against a broad range of sarbecoviruses

Using computational analysis, the team determined what RBD mutations could escape the antibody from binding. They found only a few RBD mutations disrupt the binding of this antibody. The substitution of the residue at position 504 gave the most significant disruption in binding.

When they replicated a pseudotyped SARS-CoV-2 virus in the presence of the S2X259 antibody, the only mutation they found caused by selective pressure was G504D. This mutation has rarely been seen in human isolates so far.

The selection of a single escape mutation suggests the region targeted by the antibody might not tolerate amino acid substitutions without changing viral fitness. Hence it is conserved across different sarbecoviruses. Thus, there is a high barrier for the emergence of mutations against this antibody, suggesting it could become key in combating the pandemic.

When Syrian hamsters were challenged with SARS-CoV-2, with the antibody administered 48 hours before virus infection, the authors found more than two orders of magnitude decrease in virus in the lungs compared to hamsters that did not receive any treatment. In addition, the antibody also protected hamsters infected with the B.1.351 strain.

The detection of a large variety of sarbecoviruses in bats and other mammals, along with the increased human-animal interactions, makes it likely that more cross-species transmission of viruses can occur. With increasing evidence that antibodies targeting the RBD form a major proportion of neutralizing activity, RBD-based vaccines could elicit high levels of antibodies like S2X259 with high potency. Such strategies can help overcome the current COVID-19 pandemic and help prepare for future sarbecovirus infections.

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Guide to the Proper Consumption of Healthy Foods

We all want to incorporate as many healthy foods in our diet as possible, but sometimes we aren’t sure what the right dose is. Although there are foods that are considered healthy due to the many nutritional benefits they provide us, excess consumption and incorrect dosage can also turn a good thing bad. The following list includes 10 products that are known for their health benefits, along with tips that will help you continue to enjoy their benefits and taste wisely.

1. Tomatoes
Lycopene, the red pigment in tomatoes, is an antioxidant with many breakthrough benefits. It helps to reduce the risk of various types of cancer, contributes to the protection of the heart and blood vessels, reduces cholesterol in the body, maintains eye and skin health and more. However, excess consumption of tomatoes stimulates the lining of the esophagus and may cause reflux, which is the rise of acids from the lining of the stomach to the esophagus. In addition, tomatoes contain a toxic alkaloid called solanine, and excess consumption may lead to abdominal pain, nausea, headaches and other symptoms that characterize poisoning.

How to correctly consume the product
People who don’t suffer from reflux or joint or joint problems can eat 3-4 tomatoes a day or drink one and a half cups of tomato juice. At the same time, it is recommended to incorporate cherry tomatoes, which contain less solanine, and therefore may cause fewer side effects.

2. Omega 3 and fish oil
Omega-3 fatty acids have many benefits that help maintain our health. These acids fight inflammation in the body, play an important role in the development of cells, reduce the risks of heart disease and more. Since most diets are low in omega-3, omega-3 dietary supplements, such as fish-derived supplements, are gaining popularity. However, studies have shown that excess omega-3 consumption may be harmful, especially for people who a prone to bleeding or taking blood thinners. In addition, consuming high amounts of fish oil may cause an excess in vitamin A which may have toxic effects especially for children and pregnant women.

How to correctly consume the product
Omega 3 fatty acids are essential for good health, but to avoid  damage it is recommended to consume 1-6 gm of it daily and no more.

3. Nutmeg
Nutmeg is as a spice with a unique taste, often used in cakes, sauces, soups and desserts, and in low doses provides a sweet and delicate taste for meals. Some of its benefits are also used to treat gastrointestinal problems, relieve joint pain, release muscle muscles and stimulate blood flow. However, nutmeg contains a compound called myricetin, which in excess may lead to nausea, dizziness, pain, and arrhythmias. 

How to correctly consume the product

Although nutmeg has many advantages, it is not recommended to consume more than 10 grams of nutmeg at a time, as higher doses have been shown to cause symptoms of poisoning.
 
4. Coffee
Coffee is a delicious and tasty beverage, which in several studies has been associated with many health benefits, including reduced risk of liver disease, type 2 diabetes, Parkinson's disease, and other degenerative diseases. However, an excessive amount of coffee may cause some damage. Canadian researchers have found that excess coffee may lead to changes in the nervous system, insomnia, abdominal pain, palpitations, and muscle tremors.

How to correctly consume the product

Because caffeine has a different effect on different people, some of us can drink a lot of coffee while others may experience symptoms even after small amounts of caffeine. The guiding rule, in this case, is consumption of up to 400 milligrams of coffee per day, i.e. no more than 4 cups.healthy foods

5. Cruciferous vegetables
Cruciferous vegetables are the name for the family of vegetable which includes broccoli, cabbage, Brussels sprouts, kale, and other green vegetables. These vegetables are a great source of protein, fiber, and vitamins, and may also help decrease the risk of cancer, atherosclerosis and heart disease. Their great advantages have given many of us reason to incorporate them into our daily veggie intake, both in salads and as bases for green shakes or fresh vegetable juices. However, they contain a compound of ingredients called thiocyanates that can interfere with the body's ability to absorb iodine. This problem may contribute to the under-activity of the thyroid, which is characterized by an enlarged thyroid, weight gain, dry skin, digestive problems and more.

How to correctly consume the product

Cruciferous vegetables are healthy and nutritious, but in order to enjoy their benefits, the recommendation is to consume between 1 and 2 servings per day. For people with a thyroid problem, consult a doctor about the recommended amount.
 
6. Cinnamon
Cinnamon is a flavor-rich antioxidant and has been shown to have anti-inflammatory properties, help maintain low blood sugar levels, reduce the risk of heart disease, and protect against diabetes and degenerative diseases. However, cinnamon contains high amounts of a compound called coumarin, which can be harmful in large doses, and according to studies may lead to toxicity in the liver and other diseases.

How to correctly consume the product

It is important to know that there are two main types of cinnamon, which have different coumarin: Cassia cinnamon, also known as plain cinnamon, and Ceylon cinnamon which contains less of the compound. Since the recommended daily intake of coumarin is 0.1 milligrams per kilogram of body weight, it is recommended to swap plain cinnamon for Ceylon cinnamon and consume no more than 5 grams (one teaspoon) per day. If you rarely consume cinnamon, eating more than one teaspoon occasionally is not a problem. But its best not to overdo it.healthy foods


 7. Liver
Liver is among the healthiest and most nutritious parts of beef since it is very rich in many essential nutrients such as iron, B12, vitamin A, and copper. However, studies have shown that the large amount of copper and vitamin A can cause problems when consumed in excessive quantities. 100 grams of beef liver contains more than 6 times the recommended dietary intake of vitamin A and 7 times the amount of copper, and because vitamin A is stored in our body, it can cause symptoms of toxicity, including vision problems, bone pain and increased risk of fractures, nausea, and vomiting.
 
How to correctly consume the product

Although the liver is very healthy and nutritious, it is very important not to consume it on a daily basis. A nice portion once a week will provide you with adequate access to all of its nutritional benefits.

8. Egg whites
Eggs are highly nutritional. In one egg you can find all 9 protein acids, which protect eye health, fight off heart disease, and increase good cholesterol. Protein is a very important food group, but people who consume eggs on a daily basis should pay attention and avoid excessive consumption of egg whites. This is because many animal proteins cause the body to produce growth hormones that promote aging and increase the risk of cancer, especially breast cancer. Egg whites are also problematic for people who suffer from various diseases, including fatty liver, arthritis, kidney failure and more.

How to correctly consume the product

For those who don’t suffer from ailments, you can consume up to 5 eggs per week. People who need larger amounts of protein such as vegetarians, children, athletes, and other special groups may do so with the advice of a dietician or a doctor. At the same time, for those suffering from problems such as diabetes or heart disease, it is important to receive consultation regarding egg white consumption. When calculating how much eggs you’ve eaten don’t forget to consider eggs consumed in other forms such as in cakes, for example. For those who, for certain reasons, can’t eat egg whites, protein can also be obtained from plants such as beans, nuts, seeds, and whole grains.healthy foods

9. Green tea
Green tea is generally considered a healthy and safe drink for people who don’t suffer from medical problems. It helps normal sleep, promotes blood flow in the body, relieves internal inflammation, strengthens the immune system and helps digestion problems. However, the variety of these benefits cause many to treat it almost as a drug, and in doing so, consume it excessively throughout the day. Flavonoids in tea, which are compounds that can be used as antioxidants, can bind iron mainly from plant sources or iron supplements and inhibit its absorption in the body. They may also inhibit the absorption of calcium.

How to correctly consume the product

Don’t treat green tea as a medicine or a substitute for water, and be sure to drink between 2-3 cups a day and no more. In addition, to maximize the absorption of iron from a meal or iron supplements, it is recommended to avoid drinking the tea together with food. Also, since green tea stimulates metabolism, it is not advisable to drink it on an empty stomach. This restriction on the amount of tea is especially important for people with iron deficiency, anemia, or osteoporosis.

10. Quinoa

Quinoa is a very popular and healthy food that serves as a good source of protein, contains magnesium, minerals, and vitamins, and a large amount of lysine, an amino acid that is responsible for repairing tissues in the body. However, excess fiber consumption may lead to contractions and reduce the body's ability to absorb nutrients. Although most foods rich in fiber can lead to these problems, quinoa digestion is the most difficult and problematic for the body.

How to correctly consume the product

To avoid cramping that may lead to unpleasant digestive problems and constipation, it is important to drink enough water when consuming quinoa. In addition, it is also important to pay attention to portion size, because quinoa contains a significant number of calories even though many consider it a diet food. The recommended amount is half a cup and no more.

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BP drug shows promise for treating Parkinson's

Felodipine, a prescribed drug to treat high blood pressure, has shown promise against Parkinson's, Huntington's and forms of dementia in studies carried out in mice and zebrafish at the University of Cambridge.

In a study published in the journal Nature Communications, scientists have shown in mice that felodipine may be a candidate for re-purposing. A common feature of neurodegenerative diseases is the build-up of misfolded proteins. 

These proteins, such as huntingtin in  Huntington's disease and tau in some dementia, form "aggregates" that can cause irreversible damage to nerve cells in the brain. 

A team led by Professor David Rubinsztein used mice that had been genetically modified to express mutations that cause Huntington's disease or a form of Parkinson's disease, and zebrafish that model a form of dementia. 

Felodipine was effective at reducing the build-up of "aggregates" in mice with the Huntington's and Parkinson's disease mutations and in the zebrafish dementia model. The treated animals also showed fewer signs of the diseases.

"This is the first time that we're aware of that a study has shown that an approved drug can slow the build-up of harmful proteins in the brains of mice using doses aiming to mimic the concentrations of the drug seen in humans," said Professor Rubinsztein

The hypertension drug was able to slow down progression of these potentially devastating conditions and "so we believe it should be trialed in patients," he added. 

In healthy individuals, the body uses a mechanism to prevent the build-up of such toxic materials. This mechanism is known as autophagy, or 'self-eating', and involves cells eating and breaking down the materials. 

"This is only the first stage, though. The drug will need to be tested in patients to see if it has the same effects in humans as it does in mice. We need to be cautious, but I would like to say we can be cautiously optimistic," said Professor Rubinsztein.

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A protein in your brain can be your weapon against Alzheimer’s disease

Researchers have found that a protein that regulates white blood cells in the human brain could protect against Alzheimer’s disease.

The results  suggest that this protein, called CD33, could have important implications in the fight against Alzheimer’s disease.

“Immune cells in the brain, called microglia, play a critical role in Alzheimer’s disease,” explained  co-author of the study.

“They can be harmful or protective. Swaying microglia from a harmful to protective state could be the key to treating the disease,” the author added. Scientists have identified the CD33 protein as a factor that may decrease a person’s likelihood of this disease.

Now, this research has shown that the most common type of CD33 protein plays a crucial role in modulating the function of microglia. “The fact that CD33 is found on microglia suggests that immune cells can protect the brain from Alzheimer’s disease under the right circumstances,” said the  first author of the study.

Alzheimer’s disease affects more than 44 million people around the world. “These findings set the stage for future testing of a causal relationship between CD33 and Alzheimer’s Disease, as well as testing therapeutic strategies to sway microglia from harmful to protecting against the disease – by targeting CD33,” said the researcher.

“Microglia have the potential to ‘clean up’ the neurodegenerative plaques, through a process called phagocytosis — so a therapy to harness this ability to slow down or reverse this mental health disorder can be envisioned,” he said.


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