Nida Patel Journal Week 3

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Purpose

  • This assignment' purpose is to familiarize us with academic articles and comprehending the materials and concepts in an applicable way. The goal of the assignment is to develop our own skills while using academic articles, analyzing them in a more comprehensive fashion.

Defined Terms

  1. Angiotensin: A drug that is used to lower blood pressure. An angiotensin-converting enzyme inhibitor is a type of antihypertensive agent. Also called ACE inhibitor (NCI Dictionaries).
  2. Dipeptidyl: Catalysis of the hydrolysis of N-terminal dipeptides from a polypeptide chain (Amigo, 1999).
  3. Peptidase: Any enzyme that catalyzes the splitting of proteins into smaller peptide fractions and amino acids by a process known as proteolysis.A type of enzyme that is capable of breaking down polypeptide chains into single amino acids which can then be used by the body (Biology Online, 2020)
  4. Infectivity: The characteristic of a disease agent that embodies capability of entering, surviving in,and multiplying in a susceptible host (Biology Online, 2020).
  5. Pathogenesis: The origin and development of disease (Biology Online, 2020).
  6. Residue: any of the monomers comprising a polymer, or any of the parts that integrate to make up a larger molecule (Biology Online, 2020)
  7. Orthologue: a gene, protein, or biopolymeric sequence that is evolutionarily related to another by descent from a common ancestor (Oxford Dictionary of Biochemistry and Microbiology, 2020)
  8. Steric: Pertaining to stereochemistry (Biology Online, 2020)
  9. Transmission: A passage or transfer, as of a disease from one individual to another or of neutral impulses from one neuron to another (Biology Online, 2020)
  10. Palm Civet: "Any of various small to medium-sized, chiefly arboreal cats of the civet family, of southeastern Asia, the East Indies, etc., with a spotted or striped coat and a long curled tail"(Dictionary.com)

Article Outline

Abstract and Introduction

  • 2019-nCoV originated in Wuhan, China. Transmission to humans occurred in the animal market through bats and palm civets.
  • Research done prior has established the interactions between SARS-CoV spike protein receptor-binding domain and host receptor angitensisn-converting enzyme 2.
    • Produces similar symptoms to SARS-CoV
  • SARS-CoV receptor-binding domain has a core structure, in its crystal structures it can bind to ACE2
  • The purpose of this research was to identify the mechanisms as to which 2019-nCoV binded and acted within its host using its similarities to SARS-CoV.
  • The goal of the paper is to understand the virus in order to potentially create a vaccine or treatment option for the virus

Materials and Methods

  • The software PYMOL and Coot were used to construct structural models
  • Geneious Prime and Juke-Cantor were used to model genetic distance and phylogenetic relationships between SARS-CoV and 2019-nCoV
  • Software Clustal Omega was used to create sequence alignments

Results

  • Percent similarities between SARS-CoV and 2019-nCoV
    • Spike Protein: 76%-78%
    • Spike Protein RBD: 73%-76%
    • Spike Protein RBM: 50%-53%
  • Due to the sequence similarities between 2019-nCoV and SARS-CoV it suggests that the 2019-nCoV shares the same receptor angiotensin-converting enzyme 2 (ACE2)
  • Only one insertion/deletion occurs in the RMB of 2019-nCoV in comparison to SARS-CoV
  • Figures
    • Figure 1A:Illustrates the interaction between ACE2 and RBD of SARS-CoV spike protein. Depicts the RBM interacting with RBD and thus ACE2.
    • Figure 1B:Shows the 5 critical residues of CE2 binding in 2019-nCoV
    • Figure 1C:Shows the interaction between SARS-CoV RBD and ACE2
    • Figure 1D:Shows the interaction between 2019--nCoV RBD and ACE2
    • Figure 2:A depiction of the spike protein sequences of selected lineage b coronaviruses.
    • Figure 3A:Sequence Alignments of Human-SARS-2002, Civet-SARS-2002, Bat-SARS-2013, and 2019-nCoV.
    • Figure 3B:Sequence similarities between SARS-CoV and 2019-nCoV in spike protein, RBD, and RBM.
    • Figure 3C: Sequence similarities between MERS-CoV and HKU4 virus in spike protein, RBD, and RBM.
    • Figure 4A:depicts changes in the 5 residues if ACE2 orthologues
    • Figure 4B:interactions between SARS-CoV RBD and Civet ACE2.
    • Figure 4C:interactions between 2019-nCoV RBD and Civet ACE2 receptor.

Discussion

  • Establishes 2019-nCoV to use ACE2 as its receptor in host
  • 2019-nCoV uses ACE2 although with less efficiency than the 2002 strain, but more efficiency than the 2003 strain.
  • 2019-nCoV transmitted from civets prior to mutation to adapt to Civet ACE2

Future Direction

  • Potential drug tests that would inhibit or alter binding site so 2019-nCoV is prevented from binding to ACE2 to remove entry of the virus within the host completely.

Conclusion

  • 2019-nCoV does bind to ACE2 receptor proteins within its host. In this paper they were able to identify critical residues and the spike protein compatibility within the ACE2 based on previous research establishing this relationship..

Critical evaluation

  • The article author's depicted the relationship between 2019-nCoV and ACE2 was explained and depicted very well within the article with use of graphs and details explanation of figures and concepts. The only lacking issue could be the methods page which lack detail. The lack of detail would make it difficult to replicate the results and could therefore be seen as an issue.


Template Links

Assignment Pages


Individual Journal Pages

Class Journal Pages

Acknowledgements

  • I copied and modified the protocol shown on the week 3 page.
  • I acknowledge, Taylor Makela ,who I contacted over the phone to explain the formatting style to me.

"Except for what is noted above, this individual journal entry was completed by me and not copied from another source."23:54, 23 September 2020 (PDT)

References

  1. Palm civet. (n.d.). Retrieved September 23, 2020, from https://www.dictionary.com/browse/palm-civet?s=t
  2. Transmission Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/transmission
  3. Pathogenesis Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/pathogenesis
  4. Infectivity Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/infectivity
  5. Peptidase Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/peptidase
  6. Residue Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/residue
  7. Steric Definition and Examples - Biology Online Dictionary. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/steric
  8. NCI Dictionary of Cancer Terms. (n.d.). Retrieved September 24, 2020, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/angiotensin-converting-enzyme-inhibitor
  9. The Dictionary of Cell and Molecular Biology. (2007). Angiotensin. Lackie, J.M. Elsevier Science & Technology. Retrieved September 23, 2020 from https://ebookcentral-proquest-com.electra.lmu.edu/lib/lmu/reader.action?docID=311420#
  10. The Dictionary of Cell and Molecular Biology. (2007). Angiotensin. Lackie, J.M. Elsevier Science & Technology. Retrieved September 23, 2020 from https://ebookcentral-proquest-com.electra.lmu.edu/lib/lmu/reader.action?docID=311420#
  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
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