ACE2 – BioQuakes

Tag: ACE2

An article published in August of this year identifies how the Coronavirus is able to jump from one species to another. Since the discovery of the COVID-19, the disease caused by the virus SARS-CoV-2, in 2019, many scientists have wondered how SARS-CoV-2 infiltrates cells by hijacking a protein called ACE2 which is found on human cells. At first, many believed that the ACE2 protein was required for infection, but recent discovery from the Virginia School of Medicine reveals that SARS-CoV-2 can use multiple pathways to enter cells. A good example to describe this discovery is a house. To the virus, ACE2 is the front door, but if the front door is blocked, the virus can use other proteins to enter the cells which can serve as a back door or windows in the “house.” This is concerning as SARS-CoV-2 is able to adapt to different proteins that serve as the doors into cells of other species.

After discovering that SARS-CoV-2 has the ability to enter cells using proteins other than ACE2, scientists conducted further research to determine the necessity of ACE2 in the infiltration fo healthy cells. As a result, it was revealed that SARS-CoV-2 can bind to and infect cells without ACE2 being present at all. You may be wondering what proteins besides ACE2 COVID-19 and SARS-CoV-2 use to enter and infect cells. Here is one example.

An article published in the same month identifies TMPRSS2 as an endothelial cell surface protein that allows the spread of COVID-19 and SARS-CoV-2. The definition is similar to that of ACE2 as TMPRSS2 is simply another door or window that SARS-CoV-2 can use to enter healthy cells and infect them. TMPRSS2 is commonly found in the respiratory and digestive tracts which is a supporting factor to why the Coronavirus may encounter this protein. For example, someone infected with COVID-19 may sneeze near you resulting in you breathing the virus into your respiratory tract.

In addition, an article published in the summer of 2022 explains an experiment done in order to determine the structure of the TMPRSS2 protein. The results section of the article confirms that TMPRSS2 is composed of three domains and three subdomains. An image of the protein shows tertiary protein structure surrounding the protein which is integrated into the membrane. The experiment allows us to see how similar TMPRSS2 is to ACE2 and how an antigen is able to bind to either protein and enter the membrane, but, how can this be prevented?

Although SARS-CoV-2 can enter cells in our body and infect them by entering protein channels such as ACE2 on the cell membrane, cells can create antibodies that attach to their cell membranes. In AP Bio class, we learned that in adaptive immunity, B-cell antibodies bind to foreign antigens while also inhibiting B cells to divide. B cells are then able to create B Memory Cells which recognize a foreign disease such as COVID-19 if it enters the body multiple times. B cells which are activated by B-Cell antigens, can protect our cells and prevent SARS-CoV-2 from infecting our cells by entering through ACE2 channels.

I agree that these new findings have helped us understand how SARS-CoV-2 enter healthy cells allowing them to jump species, but I also believe there is more to discover about both of these diseases such as the question of whether or not a variant of SARS-CoV-2 can be created that is able to bi pass antibodies and enter cells at the same rate it would before vaccination or first infection. ACE2 and TMPRSS2 have been around for a while but we are just now discovering how proteins like them allow diseases to jump species. What do you think?

Genetic Variation the Savior

By ellectron

On April 30, 2023

In Student Post

In the article “Genetic variation in the SARS-CoV-2 receptor ACE2 among different populations and its implications for COVID-19,” published in Nature Communications, the authors explore the genetic variation in the ACE2 receptor across different populations and its potential impact on COVID-19 susceptibility and severity. The ACE2 receptor is a key entry point for the SARS-CoV-2 virus into human cells. Its expression level and genetic variants may affect the virus’s ability to infect and replicate within the host. Therefore, understanding the genetic variation in ACE2 among different populations can provide insights into the different susceptibilities and severity of COVID-19 seen across the world. The authors analyzed genetic data from various global populations and found that there is significant genetic variation in ACE2 between populations. Specifically, they identified several ACE2 variants that are more prevalent in certain populations, including a “variant that is more common in East Asian populations” and may affect the receptor’s expression level.

The authors also conducted in vitro experiments – medical procedures, tests, and experiments that researchers perform outside of a living organism – to investigate the impact of these ACE2 variants on SARS-CoV-2 infection. They found that some variants, such as the one more prevalent in East Asian populations, led to reduced viral entry and replication, while others did not significantly affect viral infection. These findings suggest that genetic variation in ACE2 may contribute to the different COVID-19 outcomes observed across different populations. For instance, the higher prevalence of the ACE2 variant in East Asian populations may explain why these populations had a lower incidence of severe COVID-19 despite being initially hit hard by the pandemic. Furthermore, the author highlights the importance of considering genetic variation when developing COVID-19 treatments and vaccines. For instance, vaccines that were designed based on the original strain of SARS-CoV-2 may be less effective against strains that have evolved to better utilize ACE2 variants prevalent in certain populations. Overall, the article sheds light on the genetic variation in ACE2 among different populations and its implications for COVID-19 susceptibility and severity. The authors’ findings show the importance of taking genetic diversity into account when studying diseases and developing treatments and vaccines, particularly in the context of a global pandemic. In our recent DNA unit in class genetic variation was one of the topics of discussion, genetic variation is extremely important for the survival of a population as there is an easier chance that the species will be able to adapt and survive in different situations. Without genetic variation, many species can die out and therefore including the topic of genetic variation in viruses like covid-19 is extremely detrimental to the survival of humans when fighting this illness.

How Having Allergic Asthma Can Protect an Individual From COVID-19

By DNAva

On December 8, 2022

In Student Post

Scientists have found that individuals with asthma are, in fact, less susceptible to COVID-19. One could question how a pre-existing health condition could actually aid in fighting off a virus? It is accurate to assume that an individual with allergy asthma would be at more risk than a perfectly healthy individual.

Allergic asthma occurs when your airways tighten when an allergen is inhaled. The same immune system proteins that are involved with excess mucus production and the tightening of airways are used to form barriers around exposed airway cells (immune system mechanism for people with allergy asthma). This information is the basis behind the studies that explains the reasoning behind why people with asthma are less susceptible to COVID-19.

When a patient has asthma, usually the development viruses such as the Flu and Strep Throat are more dangerous for them, and still these patients with asthma are at more risk when they are infected with COVID-19. The difference lies between asthma and allergic asthma. Researchers were able to identify that people with allergic asthma were not showing major symptoms to COVID-19, which was not what one would expect. Why is that?

Protein Protection

The differentiating factor that sets allergic asthma from regular asthma is a specific protein called interleukin-13 (IL-13). The normal function of IL-13 is to help fight off parasites. Normally, specific T-Cells release this protein. In response to the release of IL-13, the body produces a sticky mucus substance and compacts airways. This traps the parasite until the immune system finishes the job by killing the parasite.

However, when an individual has allergic asthma, the body mistakes harmless matter such as pollen for a parasite, and uses IL-13 when it is not needed. The researchers now need to determine how, exactly, IL-13 is protecting patients from COVID-19.

No IL-13 Present Study

Researchers conducted a study in which they would compare how cells that haven’t been treated with the IL-13 protein react when healthy and when infected with coronavirus.

It was found that the healthy cells grew in lawns that nearly resembled grassland. This area is made up of a hair-like substance called cilium. The cilia move in waves which aids in mucus movement and the excretion of anything stuck in the mucus.

On the other hand, the cells that were infected with the coronavirus had a much different reaction. The cilia lawn was no longer clear. The cilia was covered with mucus and many bald spots that seemed as if infected cells died. The infected cells were compressed out of the lawn of the cilia, and in that process they become inflated. This inflation occurs due to vacuoles in the infected cells getting blocked up with viruses. Once the infected cell gets filled up with viruses past its capacity, it explodes and releases all of the viruses that had been in the cell.

Unfortunately, it is not as simple as this singular reaction, not all cells that were in the infected lawn were affected the same way. Researchers noticed that the cells that were attached to the cilia were infected with SARS-CoV-2, but the goblet cells, which are mucus producing cells, were barely affected. The researchers found that a protein called ACE2 is present on the surface of ciliated cells more commonly that goblet cells. With this finding, the researchers can assume that ACE2 is the protein receptor that allows SARS-CoV-2 to enter the cell.

IL-13 Present

Now the researchers conducted a second study in which they will coat the cell in the IL-13 protein and compare how the cell reacts when infected with coronavirus. The celia lawn surface with the IL-13 present has a lot less inflated dying cells on its surface and the movement of the cilia was much less rapid. This decrease in movement indicates that the mucus is present in the cilia for much longer than when IL-13 is not present. It was made clear that the IL-13 protein acted as a protectant towards the infection.

They later found out that untreated cells, once infected with SARS-CoV-2, release bursts of mucus. Whereas the IL-13 cells keep the mucus stored. Furthermore, it is known that IL-13 proteins produce a sticky mucus that has the ability to trap viruses before they get the chance to infect the cell. So, this excess mucus that is present in the treated cells can make sure the virus is out of the lungs before the damage has been done. Researchers also found A thick layer of keratan sulfate that was developed on the cell’s surface that was treated with IL-13, which protects them against SARS-CoV-2 from coming into contact with the cell.

In addition to protecting the cells, the IL-3 protein causes cells to produce less ACE2. And with less ACE2, not as many SARS-CoV-2 can come into the cell, since ACE2 is the SARS-CoV-2 receptor.

There is so much unknown about IL-3, and researchers are still trying to determine specific properties of this protein. Scientists are eager to find out more about IL-13 as they think this protein can lead to new treatment findings.

This new information about how people with allergy asthma react to COVID-19 can be looked at as a positive because it’s one thing about having allergy asthma that actually benefited the individual!

Changing Composition of SARS-CoV-2/Understanding the Alpha Variant in England

By rokhsarscov2

On January 4, 2022

In Student Post

Since its emergence in the Fall of 2020, the original SARS-CoV-2 variant of concern (VOC) rapidly became the dominant lineage across much of Europe. Although, simultaneously, several other variants of concern were identified globally. Like B.1.1.7 or the Alpha Variant (first mutation of SARS-CoV-2 found to be more transmissible), these VOCs possess mutations thought to create only partial immunity.

Researchers are understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant. This is where scientists in the UK examined trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spanned from January 31st of 2021 to May 15th of 2021.

Through this data, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label of Delta) spread rapidly, becoming the dominant variant in England by late May, similarly to the Alpha Variant.

Shown by many mutations in the spike protein receptor (RBD), studies suggest B.1.1.7 is 50–80% more transmissible with greater severity than previously circulating Covid Variants. B.1.1.7 rose rapidly, from near 0% to over 50% in under two months, and soon made up greater than 98% of sequenced samples in England. Its rapid spread necessitated a third lockdown in England during last January. Subsequent spread in Europe and North America has highlighted the threat this variant poses to a continued alteration of the Coronavirus.

The 69–70 deletion in B.1.1.7′s Spike gene causes PCR tests to return negative results for that gene target which is a major problem when identifying and testing for Covid. One of the most important changes in lineage of B.1.1.7 seems to be a spike protein substitution of N501Y, a change from asparagine to tyrosine in amino-acid position, that enhances transmission. These alterations can change antibody recognition while also affecting ACE2’s (receptor protein) binding specificity which can then lead to the virus becoming more infectious. We are seeing a pattern of the same type of mutation in Covid consistently.

An example of a similar mutation that has been recent is the new Omicron variant out of South Africa. Omicron is similar in which their has been a specific change in the spike protein where antibody recognition is limited and it is highly transmissible between any living organism. Our class has understood and studied the importance of our body being able to identify and create an antibody for the specific antigen being displayed by a pathogen. These mutations within the spike protein allow another immune response to happen which a different antibody has to be created to mark the different antigen being displayed. Unfortunately, this will be a continuing problem without vaccine mandates since it gives the virus more time to mutate where outbreaks like in South Africa will continue to transpire around the world.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: ACE2

COVID-19: Multiple Doors and Multiple Species

Genetic Variation the Savior

How Having Allergic Asthma Can Protect an Individual From COVID-19

Changing Composition of SARS-CoV-2/Understanding the Alpha Variant in England

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