JT Correy Journal Week 3

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Journal Week 3

The paper we will read for Journal Club 1 is: Wan, Y., Shang, J., Graham, R., Baric, R. S., & Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. Journal of virology, 94(7). DOI: 10.1128/JVI.00127-20

Purpose

The purpose of this week's assignment is to understand the interaction between the ACE2 protein in humans and the SARS-CoV spike receptor protein as well as the phylogeny of the spike protein.

Tasks

Vocabulary

Make a list of at least 10 biological terms for which you did not know the definitions when you first read the article. Define each of the terms. You can use the glossary in any molecular biology, cell biology, or genetics text book as a source for definitions, or you can use one of many available online biological dictionaries (links below). Cite your sources for the definitions by providing the proper citation (for a book) or the URL to the page with the definition for online sources. Each definition must have it's own citation, to a book or URL. Make an in text citation of the (name, year) format next to the definition, and then list the full citation in the References section of your journal page. Note that the citation should be to the exact page from which the definition was taken, not to the general home page of the the online dictionary.

  1. Angiotensin
    • a 60-kDa polypeptide hormone originating in the liver. It is converted from angiotensin I to angiotensin II by the angiotensin converting enzyme (Lackie 2007)
  2. Motif
    • A small structural element that is recognizable in several proteins (Lackie 2007)
  3. Orthologous
    • Genes that are related phylogenetically by a common ancestor and are usually similar in structure/organization (Lackie 2007)
  4. Lysine
    • an amino acid commonly found in proteins, with a r-group that has an amino group (Lackie 2007)
  5. Electrostatic
    • electrostatic forces are weak charged that repel when the same and attract when opposite at close distances. Strength is determined by strength of the charges (Lackie 2007)
  6. Asparagine
    • one of the 20 common amino acids. Asparagine is a neutral amino acid (Lackey 2007)
  7. Serine
    • one of the 20 common amino acids with a polar uncharged r group (Lackey 2007)
  8. Tyrosine
    • one of the 20 common amino acids with an aromatic and carboxylic acid as the R-group (Lackey 2007)
  9. Threonine
    • one of the 20 common amino acids with a carboxylic acid as the R-group (Lackey 2007)
  10. Envelope (in the context of an RNA virus)
    • a pseudo plasma membrane made up from lipoproteins that surround the RNA virus (Lackey 2007)

Summary

Write an outline of the article. The length should be the equivalent of 2-3 pages of standard 8 1/2 by 11 inch paper (you can use the "Print Preview" function in your browser to judge the length). Your outline can be in any form you choose, but you should utilize the wiki syntax of headers and either numbered or bulleted lists to create it. The text of the outline does not have to be complete sentences, but it should answer the questions listed below and have enough information so that others can follow it. However, your outline should be in YOUR OWN WORDS, not copied straight from the article. It is not acceptable to copy another student's outline either. Even if you work together to understand the article, your individual entries need to be in your own words.

  • What is the importance or significance of this work?
    • This article is exceedingly important because it provides much needed background on COVID-19. It was published in January of 2020, right when COVID-19 was spreading to areas outside of Wuhan, China. The authors of the article were able to clearly articulate many important aspects about how the virus works (like that COVID viruses are single-stranded enveloped RNA proteins) and where the virus came from (likely civets that passed it to bats that passed it to humans).
  • What were the goals and results of previous studies that led them to perform this work?
    • Previous studies of COVID type viruses have investigated the virus reception interactions of proteins and cells, in order to be able to predict receptors in future scenarios. Ultimately they hoped this would help prevent and/or control epidemics from becoming disasters. This previous research allowed the new study to take the sequence of the spike protein on the COVID-19 virus and compare it phylogenetically to the previous research. This allowed researches to determine where the virus came from.
  • What is the main result presented in this paper? (Hint: look at the few sentences of the introduction and restate them in plain English.)
    • This paper analyzed the receptor usage by the COVID-19 spike protein in order to establish how the virus interacts with its host ACE2 (angiotensin-converting enzyme 2).
  • What were the methods used in the study?
    • The researchers used the newly published sequence of the 2019-nCov RBD and compared it to the previous research on other COVID strains using Clustal Omega. They also phylogenetically analyzed the spike protein itself to identify where the virus may have come from using Geneious Prime. Then they produced several models to explain their results visually using PyMOL.
  • Briefly state the result shown in each of the figures and tables, not just the ones you are presenting.
    • Figure 1 displays a 3D representation of the ACE2 enzyme and the COVID RBM interaction. It labels down to the specific amino acids so it clear shows where the binding occurs. Figure one also includes a data table that categorizes different SARS strains and how well they bind to the human proteins.
    • Figure 2 displays a phylogenetic tree the has the spike protein beta lineage. This beta lineage is one of four subsections of the COVID lineage.
    • Figure 3 displays amino acid sequences of the interacting proteins. The RBM’s are in magenta, amino acids marked with asterisk indicate conserved residue. Amino acids marked with a colon have strongly conserved residues. Amino acids marked with a period have weakly conserved residues. Figure 3 also includes two tables that display the similarities in percent between the different RBD’s and RBM’s.
    • Figure 4 provides a data table that points out interesting amino acid changes by species, all in the ACE2 protein. It also provides 3D models of the protein for human and civet.
  • What light does their work shed on the origin of the SARS-CoV-2 virus (See Discussion)?
    • The short and succinct answer is that the SARS-CoV-2 virus came to humans from bats. The study also elaborates on the point that, unlike some previous COVID viruses, there is no evidence of a mutation that specifically relates to civets. In previous diseases there has been two mutations, one that is prevalent in humans and another prevalent in civets. This could mean that the civets were not an intermediate host, or that they were such a rapid intermediate host the virus did not have time to mutate. Lastly, it explains that many animals that humans have gotten diseases from before (rats, pigs, primates) show no evidence of being infected buy COVID-19, meaning they were likely not a method of transmission to humans.
  • What are the important implications of this work?
    • The authors of the study say that they want to lay a groundwork for the health community to be able to better attack the virus. It certainly reached their goal as healthcare is getting a firmer grasp on how to deal with the virus. However, I think this paper goes much farther than that. It also is informing people like us, a bioinformatics class at LMU. People outside of healthcare have read this article and thus it has already exceeded the goals of the paper. The implications stretch from helping undergraduate students in college better understand bioinformatics, to future generations being able to look back and use the results from this study to fight their own pandemics.
  • What future directions should the authors take?
    • I think that there are many ways the researches could expand on this study. Obviously thousands of people are dying daily due to COVID-19 so at this time anything to produce more information about the disease would be beneficial. Potentially they could look into what is preventing other species from getting COVID-19, if their binding sites prevent the RBM of COVID-19 from binding there may be useful information. They could also look into previous COVID viruses and see how organism were able to fight them off. Lastly, they could do further protein analysis on other parts of the virus and see if they can produce useful information.
  • Give a critical evaluation of how well you think the authors supported their conclusions with the data they showed. Are there any limitations or major flaws to the paper?
    • I think that they did a decent job of supporting their conclusions. One problem that I have with the article is that it focuses on ACE2 and the COVID spike binding to is. But it never elaborate on why this is bad or what ACE2 actually does. This could just be my lack of knowledge in the field, but I feel like I would have a significantly better grasp of the article if I understood why this binding is so bad. I felt that all the figure were very helpful in visualizing the article. The 3D models did a great job of portraying the physical protein-spike interaction. Overall, the article did achieve its goal of providing information on the interaction between the COVID-19 spike and human protein. However it could have had more background information that would have helped the more uneducated readers like myself.

Conclusion

After thorough analysis of the paper, I definitely have a better understanding of the interaction of the RBD and COVID protein spike. Through the figures I was able to understand the 3D interaction and through the writing I was able to understand the background information. The paper also did a good job of providing information about the origins/phylogeny of COVID-19 as well as the different species it can infect.

Acknowledgements

  • Ian R. Wright
    • Ian and I worked as homework partners for this week. We communicated mostly over text to work together throughout the assignment and prep for our figure 3 presentation.
  • Dr. Dahlquist
    • Dr. Dahlquist served as a coach for how to begin our pages. She also instructed the class and provided us with the guiding homework document.
  • Except for what is noted above, this individual journal entry was completed by me and not copied from another source.

Jcorrey (talk) 18:35, 23 September 2020 (PDT)

References

  • OpenWetWare. (2020). BIOL368/F20:Week 3. Retrieved September 23, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_3
  • OpenWetWare. (2020). User:BallonaBuddy (Ian R. Wright). Retrieved September 22, 2020, from https://openwetware.org/wiki/User:BallonaBuddy
  • Lackie, J. M., & Lackie, J. M. (Eds.). (2007). The dictionary of cell and molecular biology. (pp 27, 274, 304, 251, 140, 37, 383, 436, 145, 418) ProQuest Ebook Central https://ebookcentral-proquest-com.electra.lmu.edu
  • Wan, Y., Shang, J., Graham, R., Baric, R. S., & Li, F. (2020). Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Journal of Virology, 94(7). doi:10.1128/jvi.00127-20

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