BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: spike protein

A New Hope? Promising new research finds a way to treat COVID-19

Despite the recent decline in COVID-19 cases, researchers and public health officials struggle to treat and prevent new cases of the disease.  A 2022 article in the Washington post outlined the recent efforts by researchers to treat and prevent COVID-19, particularly examining monoclonal antibody treatment, a treatment that utilizes human-made antibodies to aid in the Body’s natural response.

However, according to researchers, new mutations are quickly arising which undermine the effectiveness of these treatments, making it difficult for the medical world to keep up with the virus, so biologists are turning to more novel methods.  One Quebec-based company, Sherbrooke, thinks they’ve found the solution, “We saw a sharp decline in viral loads,” says the company’s chief medical officer Bruno Maranda.

Traditional monoclonal antibody treatment has had trouble inhibiting the binding between the spike protein of the virus SARS-CoV-2 and human cells because the binding location of the spike protein is mutating quicker than researchers can adjust antibody treatment.  According to Andrés Finzi, associate professor at the University of Montréal, “there is a huge immune pressure on the virus,” indicating that it will likely continue to mutate in this way.  

 

Novel Coronavirus SARS-CoV-2 Spike Protein (49583626473)

 

 

However, scientists have noticed that certain areas of spike protein have remained rigid as the virus mutates; one such area is the stem helix.  Because of its lack of mutation, scientists believe that this area is essential to SARS-CoV-2 and if disrupted can limit its ability to mutate and cause harm to our bodies.  

Although the new drug from Sherbrooke uses 2 antibodies that attack the spike protein in a more conventional way, the new third antibody attacking the more rigid areas of the protein has proven effective in all trials that have been undertaken.

Another recent paper has also attempted to amend antibody treatment to target more stable sections of the spike protein: the fusion peptide.  According to the chief of the Antibody Biology unit of the National Institute of Allergy and Infectious Diseases, this structure “acts like a grappling hook and inserts into the human cell membrane, pulling the membrane closer to the virus membrane.”  Researchers hope to use these rigid structures to help develop more reliable treatments and preventions for COVID-19.

This system of antibodies protecting our bodies from illness is similar to what we are currently learning in Biology class.  In class, we learned that in the body’s humoral response to pathogens, B-plasma cells secrete antibodies that bind to pathogens, thereby neutralizing them, allowing them to be quickly engulfed by macrophages and destroyed.  Monoclonal antibody treatment leverages this function of antibodies, creating artificial antibodies to facilitate this interaction more strongly.

While these new developments in COVID-19 treatment are exciting, Finzi warned that “we shouldn’t underestimate the capacity of a coronavirus to mutate.”  Other scientists, including Harvard professor of pediatrics Bing Chen, believe that antibody treatment research should not take the place of other disease-fighting tactics; according to Chen “we need much more effective vaccines, for sure.”  But one thing remains true, and that is that SARS-CoV-2 continues to mutate, and will continue to be a serious problem if we fail or adequately treat and prevent it, and while the number of cases is decreasing, it still remains strikingly high for us to write off the disease as harmless.

Omicron: The Most Infectious COVID Variant Yet

Omicron has become the most infectious variant of COVID yet, even managing to re-infect people who already had COVID. According to researchers in Botswana and Africa, omicron’s ability to spread so easily is due to its 60 genetic mutations, which include 42 changes to its spike proteins.

In class, we learned about a form of endocytosis called receptor-mediated endocytosis. Receptor-mediated endocytosis occurs when ligand bind to receptor proteins on the cell membrane that match their shape. This process triggers the cell to let in the virus in a coated vesicle. In this case, the ligands are the COVID spike proteins are the receptor proteins are called ACE2. The omicron spike protein is shaped like a claw machine. Most antibodies attack the claw fingers, however, omicron keeps its “knuckles” bent to hide the parts the antibodies target. Omicron can also stick out one positively charged finger to grab onto the negatively charged receptor. This electrical attraction in omicron is three to five times greater than that of the delta variant, greatly contributing to its ability to infect the cell.Coronavirus. SARS-CoV-2

Researchers also suspect that omicron uses a mechanism unlike previous variants to enter the cell. They believe that omicron uses a backdoor compartment called an endosomes, sorting organelles part of the endomembrane system, and a protein called cathepsin L to drop its genetic material. We discussed in class that the endomembrane system also included vesicles, nuclear envelope, the Golgi body, plasma membrane, and the ER. Through this method, omicron is able to enter the cell without killing it. This is particularly significant as the virus can use the host cell to create even more of the virus to spread. Another mutation that aids the virus is a sugar molecule on the spike protein. This modification makes it difficult for antibodies to attack the virus. For these reasons, omicron has managed to evade very effective vaccines. In one case, it was found that two doses of the Moderna vaccine was only 44% effective at preventing omicron infection between 14-90 days after getting the vaccine, and only 23.5% effective between 3-6 months after getting the vaccine.

I was interested in this topic because I’ve noticed that many of my classmates have gotten infected with COVID recently, even after receiving multiple vaccines or having already being infected with COVID. We can only hope that the next mutations will not lead to a more virulent form of the virus.

2021: The Year Of The Coronavirus Variants

Alpha and beta kicked off the 2021 year, and several worrisome variants later, omicron closed it out. How omicron may come to define the pandemic’s future remains uncertain. But even as omicron comes on strong, one variant, which rose to global dominance midyear in a way variants like alpha and beta never did, continues to largely define the pandemic right now: delta.

Things had actually seemed to be looking up in some parts of the world in the late spring and early summer of 2021, a year and a half into the COVID-19 pandemic. In the United States, for instance, millions of people were vaccinated, cases of the disease were falling, and people were beginning to socialize and resume normal activities. 

But then delta hit hard. First spotted in India in October 2020, this variant of SARS-CoV-2, the coronavirus known as COVID-19, quickly swept around the world, supplanting other versions of the virus in 2021. Delta overwhelmed health care systems, tore through unvaccinated populations and showed that even the vaccinated were vulnerable, causing some breakthrough cases.  

It soon became clear why delta wreaks so much havoc. People infected with delta make more of the virus and spread it for longer than people infected with other variants, researchers reported in Clinical Infectious Diseases in August. As a result, delta infections are more contagious. Consider two scenarios in a community where no one has immunity to the coronavirus: A person infected with an earlier version of the virus — the one first identified in Wuhan, China, that set off the pandemic — might spread it to two or three others. But a person infected with delta may transmit it to five or six people.

COVID-19 Coronavirus Symptoms

Mutations similar to delta’s have appeared here and there in other variants that proved themselves capable of spreading more easily or better evading the body’s immune defenses than the original virus. That includes alpha, first spotted in the United Kingdom; beta, first characterized in South Africa; and gamma, first noted in Brazil. The recently discovered omicron variant, first described in South Africa and Botswana, also shares some of the same mutations. 

Some of delta’s grab bag of mutations are identical to those found in other variants, while others change the same protein building block, or amino acid, in a different way or pop up in the same part of the virus. For instance, alpha and omicron also have the same mutation of the 203rd amino acid in the N protein, but it is a different amino acid change than seen in delta. And some mutations are entirely new to delta. 

3D medical animation coronavirus structure

These mutations on the coronavirus’ spike protein are what define delta as delta. The spike protein helps the coronavirus attach to and enter human cells penetrating host cells and cause infection. Spike proteins as learned in AP Biology while talking about COVID-19, a spike protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. The delta variant’s version carries a unique collection of mutations, marked by yellow dots in this 3-D rendering. Some of these mutations may help the virus more easily infect cells or hide from antibodies.

Though more recently in 2022 most of the population is getting the omicron variant, we must not forget the dominant variant that took control of the world and harmed a lot of people within a very short frame of time. Just when we thought we were out of the woods of COVID-19 during the summer of 2021, the delta variant proved us wrong.

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