{"id":215,"date":"2022-04-23T15:41:42","date_gmt":"2022-04-23T15:41:42","guid":{"rendered":"https:\/\/sites.wp.odu.edu\/science-portfolio\/?p=215"},"modified":"2022-04-23T15:41:43","modified_gmt":"2022-04-23T15:41:43","slug":"scientific-literacy-on-covid-19-and-mutated-variants","status":"publish","type":"post","link":"https:\/\/sites.wp.odu.edu\/science-portfolio\/2022\/04\/23\/scientific-literacy-on-covid-19-and-mutated-variants\/","title":{"rendered":"Scientific literacy on Covid 19 and mutated variants"},"content":{"rendered":"\n

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By: William Meade<\/p>\n\n\n\n

A severe respiratory virus known as Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV2), or Covid-19 has struck the world very fast. Since the discovery millions have been infected and hundreds of thousands have died. Even with the new Covid-19 vaccine the virus is still infecting thousands every day. Covid-19 is an effective virus due to the spike protein which allows the virus to adapt, bind, and even invade host cells. However, the spike protein has the ability to mutate on certain areas, which creates new variants of the virus. Variants such as L452R, E484K, E484Q, N501Y, and P681H. Review of these variants change in amino acid structure and chemistry results in new functions for the spike protein, which changes the overall effect of the virus on host cells.<\/p>\n\n\n\n

            The spike protein that is a part of the viruses structure we have all heard about. This spike protein is how the virus infects the human body. Spike proteins are composed of three identical chains, a membrane spanning segment, a large ectodomain that extends outward from the virus, and the spike, which is a glycoprotein (Goodsell, 2020). The reason SARS-CoV and SARS-CoV-2 goes without detection is due to the ectodomain that is lined with sugar chains that mask it from the human immune system. Spike proteins that are seen on this virus initiate the process of infecting the cell, binding to receptors and then passing the viral genome unto the human cell. <\/p>\n\n\n\n

            After the SARS-CoV virus infects the body, the spike proteins contact the human cell, afterwards the virus will then bind the specific receptor binding domains. For the case of SARS-CoV-2 it responds ACE2. The main role of ACE2 is the degradation of angiotensin II. This specific receptor is important to most tissue within the body but is expressed the highest in the kidney, lungs, and heart. The S protein or spike protein has an affinity for the ACE2 receptor. The ACE2 receptor is the most important in the human body within the lungs. ACE2 regulates the amount of angiotensin II circulating in the lungs. Angiotensin II plays a huge role in the lungs, if a patient is hypoxic, the angiotensin II can promote vasoconstriction to alleviate the hypoxia. Also regulating angiotensin II is important because if levels of angiotensin is to high within the lungs this causes pulmonary edema or fluid buildup in the lungs (Benedette Cuffari, 2021).  SARS-CoV and SARS-Cov-2 both have spike proteins and these both bind to ACE2. The S protein of both viruses is made up of two different segments called S1 and S2. The S1 domain is responsible for the association and stabilization of the S protein to the ACE2 receptor, while the S2 domain is responsible for structural rearrangement. The rearrangement of the spike protein is essential for the merging of the host cell and viral cell.<\/p>\n\n\n\n

            Once the SARS-CoV-2 virus binds to ACE2 a structural change takes place. This structural change has been shown to the main reason why creating a vaccine and stopping Covid-19 has been so tough. Once the spike protein binds to ACE2 the structural change takes place by folding in on itself. However, in the original virus this change was premature and sometimes caused the virus to collapse and make it harder to bind to cells (Fliesler, 2021).  Since, then there have been several mutations to the SARS-CoV-2 virus. Some of these mutations have had amino acid base changes that help stabilize this premature folding. This makes the virus much more infectious. <\/p>\n\n\n\n

            In all variants the letters mentioned are the amnio acids that are in the mutation, and the numbers are the position on the spike protein. In the variant L452R the amnio acid leucine changes at the 452nd<\/sup> position to arginine. L represents leucine, while the letter R represents arginine. This particular change in structure has been troubling due to the change from hydrophobic leucine to hydrophilic arginine (Joshi et al., 2021).  With this change not only does the result change from nonpolar to polar, but also neutral leucine is changed to negative charged arginine. This changes the electrostatic interaction of the amnio acids, which in turn increases the transmissibility and infectivity of the L452R variant.  <\/p>\n\n\n\n

            The variant E484Q also referred to as the co-mutant of L452R (Joshi et al., 2021)<\/p>\n\n\n\n

. The charged glutamic acid is substituted with neutral charged glutamine. This takes place at position 484 on the spike protein. Since the charged glutamic acid is substituted with neutrally charged glutamine the electrostatic change that changes from charged to neutral disrupts the interaction with spike receptor binding domain. This E484Q mutation disrupts the two hydrogen bonds on S56 and Y53 with the antibody. (Joshi et al., 2021)<\/p>\n\n\n\n

Another mutation mentioned is E484K, the 484 position is where several mutations take place. Negatively charged glutamic acid changes to positively charged lysine.  Even though both amino acids are polar, the change in charge has impacted the effectiveness of the mutation.  The E484K mutation results in several hydrogen bonds and salt bridge interactions. The hydrogen bonds and salt bridges interact with the neutralizing antibodies, however the E484K mutation disrupts these bonds with antibodies (Joshi et al., 2021).  E484K variant has been labeled the escape variant due to the ability to slip past antibodies, it also has been shown that covid-19 therapies have been ineffective (Wise, 2021).<\/p>\n\n\n\n

            In N501Y the mutation takes place at the 501 positions on the spike protein. The hydrophilic asparagine (N) is substituted with hydrophobic tyrosine(Y). Unlike the other variants the mutation does not result in any significant structural change. Scientists have found that the N501Y mutation has had little effect on antibody binding. (Joshi et al., 2021)<\/p>\n\n\n\n

However, the variant has been shown to evade antibody nullification.<\/p>\n\n\n\n

            The final variant P681H takes place at the 681st<\/sup> position of the spike protein. The P amnio acid proline is replaced with histidine (H). Proline being nonpolar changes to histidine, which is polar. The change that takes place allows the variant to be viable in aqueous environments. Because of the polarity of the new mutation the antibody binding properties have been altered.  (Joshi et al., 2021)<\/p>\n\n\n\n

            There have been several mutations to the original SARS-CoV-2 virus. The most recent one is B.1.640.2 or IHU. IHU is the research institute this strain was first identified at. This virus is said to be riskier than the delta variant and omicron variant. The IHU variant has been found to have the most mutations with 46 and 37 deletions resulting in 30 amino acid substitutions and 12 deletions. This variant has only been confirmed in 12 people. Therefore, the mutations or either not very infectious or the MRNA vaccines along with booster vaccines are significantly boosting our immune system to give us the antibodies we need to protect us from these different variants. <\/p>\n\n\n\n

Works Cited<\/p>\n\n\n\n