Scientific Literacy Essay- Seth Kreidel
Dealing with the COVID-19 pandemic has proved very difficult for many reasons, one of which is trying to prevent the spread of the disease after it mutates. Viruses tend to be very prone to mutation, and COVID is no exception especially with the new variant that was discovered in France. This new variant came to be primarily due to five mutations on the spike protein of COVID. These mutations include the following: L452R, E484K, E484Q, N501Y, and P681H.
The L452R mutation tells us that COVID’s spike protein went from having Leucine as its 452nd amino acid to having it replaced by Arginine. This mutation occurs rather late in the amino acid chain and Leucine is an amino acid that is nonpolar and hydrophobic, meaning that it does not like interacting with water. However, in this mutation, it gets replaced with arginine: a polar, hydrophilic, and positively charged amino acid. Because of this change, the amino acid in this section of the protein is not only able to interact with water, but it will also be able to interact with water, negatively charged things, and other polar things. These interactions can help the proteins fold in different types of ways and create new kinds of structures. In turn, different structures in the proteins of COVID can help it become more resilient.
When it comes to the E484K mutation, the 484th amino acid went from being a Glutamic Acid to being a Lysine. According to Wikipedia’s pages on Glutamic Acid (2022) and Lysine (2022), Glutamic Acid is an amino acid efficient in facilitating metabolism and Lysine is an amino acid important for synthesizing more proteins. Proteins essentially help drive every function of living things, which also extends to viruses. Having more proteins can help COVID become more resistant to medicine, and easier to transmit.
Another example of a mutation on the 484th amino acid is the E484Q mutation, which switches Glutamic Acid for Glutamine. Glutamine is an uncharged polar amino acid, which means that this protein will be able to make less interactions which charged amino acids. However, while this inability to create more interactions means less possibilities for the protein, it will still end up changing the structure of the protein. Different structures mean new functions for proteins.
In the N501Y mutation, in 501st amino acid has its Asparagine swapped for a Tyrosine. While both of these amino acids are uncharged and polar, the Wikipedia page on Asparagine (2022) states that this amino acid is crucial in modifying protein chains, while the Wikipedia page on Tyrosine (2022) explains that Tyrosine is efficient in creating new proteins. This is another example of a mutation that helps COVID make more proteins and carry out more functions, but the loss of this Asparagine also means that the protein will not go through as much modifications. This will result in more mutations and potentially different behaviors in this COVID variant.
The last notable mutation in the spike protein of COVID was the P681H mutation. In this mutation, Proline was switched out for Histidine on the 681st amino acid. Proline is a pretty unique amino acid compared to others and causes the protein chain to have a distinctive “bent” look to it. Swapping this amino acid out for Histidine would drastically change the shape of the protein, and thus give it an altered function. Additionally, just like the L452R mutation, the addition of a polar charged amino acid (in the case of P681H, Histidine) allows the protein to interact with other proteins in different ways, create new structures, and carry out new functions.
Understanding how a virus mutates as well as what adaptations it might develop helps us better prepare against viruses in general. However, we also need to understand how the virus affects the cell if we want to properly slow the spread of viruses. However, not all viruses act the same, and COVID has a few important components to it that help it effectively infect the cell and facilitate spreading itself to new hosts.
A notable piece of the Sars-CoV-2 virus is its spike protein. One can essentially think of spike proteins as the “skeleton key” that lets viruses break inside of host cells and infect them by producing copies of themselves inside. According to “Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus development for COVID-19” , the overall shape of the spike protein of SARS-CoV-2 roughly resembles a large head on top of a neck (Huang et al., 2020). They go on to mention that the function of the spike protein if fairly simple, in that it’s only job is to detect cells and break inside of them. They do this by recognizing a receptor on the target cell’s cell membrane before fusing it’s own membrane onto the cells. This fusion of the membranes of the cell and the virus allows the viruses to insert copies of it’s DNA into the cell, thereby infecting it. To be more specific, SARS-CoV-2 binds to the receptor ACE2 (Huang et al. 2020) to infect its target cell. Different viruses bind to different receptors so its highly valuable to know the binding site to prevent infection.
Every cell receptor has its own “job” regarding the cell, and ACE2 is no different. Medical doctors Krishna Sriram, Paul Insel, and Rohit Loomba (2020) explain that the ACE2 receptor works in cell functions that have to do with healing, such as inflammation and blood pressure. Having this receptor obstructed by a virus means that the receptor won’t be able to carry out its job. Thus, cells will struggle to heal themselves after being infected by COVID. This might explain why so many people have died to COVID.
However, since viruses are prone to mutation, this also means that the spike protein has the potential to change too. If the spike protein is changed, there is a significant chance that the virus will no longer be able to bind to the receptor. Not being able to bind the receptor obviously means that the virus will be unable to infect the cell. Virus’ tendency to mutate is a bit of a double-edged sword, as most of the time, the mutation in question will either be to their benefit or their own detriment.
When it comes to SARS-CoV-2, its mutation doesn’t seem to be harming it any. According to the New York Times in their Coronavirus World Map: Tracking the Global Outbreak (2022), SARS-CoV-2 has infected over 500 million people, and killed 6 million of them in the process. This pandemic has been detrimental to countless people around the globe, and it all traces back to a mutation. This shows us that while mutations can be harmful to a host, they can also make the host incredibly powerful.
References
Coronavirus World Map: Tracking the Global Outbreak. (2022). The New York Times. Retrieved from https://www.nytimes.com/interactive/2021/world/covid-cases.html, 2022.
Huang, Y., Yang, C., Xu, W., Xu, X., Xu, W., Liu, S. (2020). Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacological Sin. Retrieved from https://www.nature.com/articles/s41401-020-0485-4#Sec5, 2022.
Wikipedia contributors. (2022, January 24). Glutamic acid. In Wikipedia, The Free Encyclopedia.
Retrieved 03:06, February 7, 2022, from https://en.wikipedia.org/w/index.php?title=Glutamic_acid&oldid=1067590398.
Wikipedia contributors. (2022, February 5). Lysine. In Wikipedia, The Free Encyclopedia. Retrieved
03:11, February 7, 2022, from https://en.wikipedia.org/w/index.php?title=Lysine&oldid=1070104327.
Wikipedia contributors. (2022, February 3). Asparagine. In Wikipedia, The Free Encyclopedia.
Retrieved 03:32, February 7, 2022, from https://en.wikipedia.org/w/index.php?title=Asparagine&oldid=1069636081.
Wikipedia contributors. (2022, January 15). Tyrosine. In Wikipedia, The Free Encyclopedia.
Retrieved 03:33, February 7, 2022, from https://en.wikipedia.org/w/index.php?title=Tyrosine&oldid=1065890709.
Sriram, K., Insel, P., Loomba, R. (2020). What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain. The Conversation. Retrieved from https://theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-experts-explain-136928, 2022.