Yaniv Maddahi Journal Week 3

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Purpose

  • The purpose of this assignment is to develop our skills in reading academic and scholarly articles as well as even developing our own skills of analyzing and interpreting data and even creating our own outlines of the work.

Based on Reading

10 Words for which I had to look up the definition

  1. Angiotensin - A family of oligopeptides associated with increased blood pressure, mainly by causing vasoconstriction (Gonzaga, 2020)
  2. Epidemic - Occurring suddenly in numbers clearly in excess of normal expectancy, said especially of infectious diseases but applied also to any disease, injury or other health related event occurring in such outbreaks (Gonzaga, 2020).
  3. Enveloped Virus - Any of the viruses with a lipoprotein envelope surrounding the nucleoprotein core of the virus (Gonzaga, 2020).
  4. Peptidase - Any enzyme that catalyzes the splitting of proteins into smaller peptide fractions and amino acids by a process known as proteolysis (Gonzaga, 2020)
  5. Genera - Plural form of genus (Gonzaga, 2020).
  6. Orthologue - A gene, protein, or biopolymeric sequence that is evolutionarily related to another by descent from a common ancestor (Cammack, 2006).
  7. Bifurcated - Forked, with 2 branches (Allaby, 2019).
  8. Pathogenesis - The process of disease development(Allaby 2020).
  9. Salt Bridge - An electrical connection made between two half cells (Law, 2020)
  10. Palm Civet - A mainly arboreal civet that typically has pale spots or stripes on a dark coat, and powerful curved claws, native to Africa and Asia. It is often a pest of banana plantations (Stevenson, 2010).

Article Outline

  • What is the importance or significance of this work?
    • The importance of this research comes with being able to possibly identify the mechanism of binding and action for 2019-nCoV and thus being able to possibly find a cure or vaccine as this virus seems to only be getting more and more prevalent in society as well as increasingly dangerous.
  • What were the goals and results of previous studies that led them to perform this work?
    • Previous research on the receptor recognition of SARS-CoV identified interactions between the SARS-CoV spike protein and the previously mentioned ACE2. The purpose of these previous studies was to identify virus-receptor interactions and to further predict potential animal hosts as well as animal models for the viruses. Not only, but by identifying the sequence of the 2019-nCoV spike protein, the researchers were further able to apply the same predictive framework of the original SARS-CoV and thus identify possible receptor usage as well as host range of 2019-nCoV.
  • What is the main result presented in this paper?
    • In recent months there has been a tremendous increase in the appearance of the coronavirus (2019-nCoV). This version of the coronavirus produces symptoms similar to the original SARS-CoV that came about in 2002 and seems to also have similar binding patterns, suggesting that the 2019-nCoV also binds to angiotensin-converting enzyme 2 (ACE2). That being said, studies have shown other critical residues that suggest the development of human-to-human transmission of 2019-nCoV.
  • What were the methods used in the study?
    • A software by the name of PyMOL was used to construct structural figures and then a software by the name of “Coot” was used to mutate different regions of the virus model.
  • Briefly state the result shown in each of the figures and tables, not just the ones you are presenting.
    • Figure 1: This figure includes two main models, one of the models (A) depicts a green, blue, and pink region. The blue and pink are part of the virus and are the spike protein. The green is the extracellular region of Human ACE2. In C and D the authors are using the actual representation of Human ACE2 although the pink section is using the most optimized predictive model of the RBD of the virus based on the 2002- variant of SARS-CoV (C) and the current 2019 variant of the virus (D).
    • Figure 2: Phylogenetic tree depicting the beta-genus lineage of coronavirus. This is mostly a description regarding the spike protein sequences of selected lineage b coronaviruses. The sequences were aligned and compared using the Blosum62 cost matrix in Geneous Prime. The phylogenetic tree was constructed by the means of a neighbor-joining method also Geneious Prime. The graph was rendered for publication using EvolView.
    • Figure 3: Amino Acid sequence for Human-SARS-2002, Civet-SARS-2002, Bat-SARS-2013, and 2019-nCoV (A). ACE2 contacting regions are shaded as well with the asterisks indicating positions that have conserved residues. The colons indicate positions that have strongly conserved regions. The periods further indicate positions that have weakly conserved residues. (B) indicates sequence similarities of SARS-CoV and 2019-nCoV in the spike protein as well as RBD and RBM. (C) indicates sequence similarities between MERS-CoV and HKU4 virus in the spike protein, RBD, and RBM.
    • Figure 4: Civet ACE2 with Civet-CoV as well as Human-CoV. The model depicts structural analysis of civet ACE2 recognition by 2019-nCoV as well as SARS-CoV. (A) depicts changes among amino acids and different positions. (B) depicts determined structures of the interactions between SARS-CoV RBD and Civet ACE2. (C) models the interface between 2019-nCoV and Civet ACE2.
  • What light does their work shed on the origin of the SARS-CoV-2 virus?
    • The authors believe that 2019-nCoV may have also originated from bats. Not only, 2019-nCoV also recognizes ACE2 of other species such as palm civets as well as humans and therefore could have used one as an intermediate host. Not only, but this could also result in dual host species replication and transmission. 2019-nCoV does show slightly weaker binding to human ACE2 however. Thus, it is believed that either the palm civets were not intermediate hosts or if they were that the transmission occurred before sufficient mutation/adaptation occurred to ACE2.
  • What are the important implications of this work?
    • Being able to capture the different mechanisms by which a virus can interact with a host receptor not only makes it easier to discern the actual mechanism of action of the virus itself but also allows researchers to make predictions about the behavior of a virus or even ways in which to tackle exterminating the virus. Through their studies, the researchers were able to determine that the 2019-nCoV uses the same interactions with ACE2 although with less efficiency than the 2002 strain and more efficiency than the 2003 strain. The interaction with ACE2 is considered an integral part to the virus’s ability to act. Interestingly, 2019-nCoV has been found to have evolved the ability to transmit among humans and could possibly be a reason for its seen effects among populations. Scientists are closely monitoring the virus for mutations that could potentially enhance the affinity of the virus to ACE2.
  • What future directions should the authors take?
    • I believe the authors should continue testing among the pigs, ferrets, cats, and nonhuman primates in order to continue to study the mechanism of action for 2019-nCoV. Further, I believe they should continue to test for possibly what mechanism makes 2019-nCoV so favorable for
  • 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 believe the authors did a great job explaining their work with the graphs. All figures had explanations which followed their explanations in the results section. I do feel that having still images does pose a limitation to the actual nature of the interaction as well as the ways in which it may be changing over time. That being said, I do not see any major flaws in the writing as from my perspective it seemed very well-rounded. I would say that the researchers did use many predictive models which do set a certain amount of uncertainty with their work.


Conclusion

  • The purpose of this lab was met as we did ultimately read, analyze, and cohesively outline the academic article. Through the reading, explaining, and reiterating in our own words the content of the article. In completing the assignment we identified words for which we did not know the meaning, outlined the article, and explained the tables and figures. As a result, we have been able to further cultivate our academic minds at extrapolating information from scientific readings and cohesively constructing an outline.


Template

BIOL368/F20

Yaniv Maddahi

Yaniv Maddahi Template

Assignment Week

Individual Journal Pages


Class Journal Pages

Acknowledgements

  • I acknowledge my TA, Annika Dinulos,who I contacted regarding a question for one of my assignments.
  • I copied and modified the protocol shown on the Week 1 page.
  • I copied and modified the protocol shown on the week 3 page.
  • I acknowledge Dr. Dahlqusit with whom I met via Zoom office hours regarding questions on interpreting the tables and figures.

"Except for what is noted above, this individual journal entry was completed by me and not copied from another source."Yaniv Maddahi (talk) 17:45, 22 September 2020 (PDT)

References

  1. Gonzaga, M. (2020, January 27). Angiotensin Definition and Examples - Biology Online Dictionary. Retrieved September 19, 2020, from https://www.biologyonline.com/dictionary/angiotensin
  2. Gonzaga, M. (2020, January 27). Epidemic Definition and Examples - Biology Online Dictionary. Retrieved September 19, 2020, from https://www.biologyonline.com/dictionary/epidemic
  3. Gonzaga, M. (2020, January 27). Enveloped virus Definition and Examples - Biology Online Dictionary. Retrieved September 19, 2020, from https://www.biologyonline.com/dictionary/enveloped-virus
  4. Gonzaga, M. (2020, January 27). Peptidase Definition and Examples - Biology Online Dictionary. Retrieved September 19, 2020, from https://www.biologyonline.com/dictionary/peptidase
  5. Gonzaga, M. (2020, January 27). Genera Definition and Examples - Biology Online Dictionary. Retrieved September 19, 2020, from https://www.biologyonline.com/dictionary/genera
  6. Cammack, R., Atwood, T., Campbell, P., Parish, H., Smith, A., Vella, F., & Stirling, J. (Eds.). (2006). orthologue. Oxford Dictionary of Biochemistry and Molecular Biology. : Oxford University Press. Retrieved 19 Sep. 2020, from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-14381.
  7. Allaby, M. (Ed.)(2019). Bifurcate. A Dictionary of Plant Sciences. : Oxford University Press. Retrieved 19 Sep. 2020, from https://www.oxfordreference.com/view/10.1093/acref/9780198833338.001.0001/acref-9780198833338-e-778.
  8. Allaby, M. (2020). pathogenesis. In A Dictionary of Zoology. : Oxford University Press. Retrieved 19 Sep. 2020, from https://www.oxfordreference.com/view/10.1093/acref/9780198845089.001.0001/acref-9780198845089-e-6423.
  9. Law, J., & Rennie, R. (Eds.). (2020). salt bridge. A Dictionary of Chemistry. : Oxford University Press. Retrieved 19 Sep. 2020, from https://www.oxfordreference.com/view/10.1093/acref/9780198841227.001.0001/acref-9780198841227-e-3638.
  10. Stevenson, A., & Lindberg, C. (Eds.). (2010). palm civet. New Oxford American Dictionary. : Oxford University Press. Retrieved 19 Sep. 2020, from https://www.oxfordreference.com/view/10.1093/acref/9780195392883.001.0001/m_en_us1275167.
  11. Wan, Y., Shang, J., Graham, R., Baric, R., & Li, F. (2020, March 17). Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Retrieved September 23, 2020, from https://jvi.asm.org/content/94/7/e00127-20
  12. OpenWetWare. (2020). BIOL368/F20:Week 1. Retrieved September 21, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_1
  13. OpenWetWare. (2020). BIOL368/F20:Week 3. Retrieved September 22, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_3