Dcartmel Week 11

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Purpose

  • The purpose of this assignment is to analyse and critique a particular scientific article about the coronavirus and find out how similar it is to previous related viruses.

Definitions

  1. Infectivity- the characteristic of a disease agent that embodies capability of entering, surviving in, and multiplying in a susceptible host (BiologyOnline, 2020).
  2. Palm civet- any of several black-spotted or black-striped yellowish gray or brownish gray civets of Paradoxurus or related genera that are widely distributed in southeastern Asia and the East Indies (Merriam Webster, 2020).
  3. Orthologue- a gene, protein, or biopolymeric sequence that is evolutionarily related to another by descent from a common ancestor, having diverged as a result of result of a speciation event (Oxford Dictionary of Biochemistry and Molecular Biology, 2008).
  4. Phylogram- a phylogenetic tree that indicates the relationships between taxa and also conveys a sense of time or rate of evolution ((Oxford Dictionary of Biochemistry and Molecular Biology, 2008).
  5. Putative- denoting a supposition or inference based on what was commonly believed, reputed, or deemed rather than on a direct evidence (BiologyOnline, 2020).
  6. Bifurcate- forked with two branches (A Dictionary of Plant Sciences, 2019).
  7. Pathogenesis- the generation and production, or the origin and development of a disease (Oxford Dictionary of Biochemistry and Molecular Biology, 2008).
  8. Conserved- describing a tendency to invariance in corresponding residues or sequences of residues of encoded macromolecules obtained from specimens of genetically different sources (Oxford Dictionary of Biochemistry and Molecular Biology, 2008).
  9. Steric- relating to effects involving arrangements of atoms in space (Oxford Dictionary of Biochemistry and Molecular Biology, 2008).
  10. Salt bridge- an electrical connection made between two half cells (A Dictionary of Chemistry, 2016).

Outline of Article

What is the importance or significance of this work

  • The importance of this work is that it utilizes past research and knowledge about SARS-CoV to make predictions about various aspects of the 2019-nCoV virus. This work identifies that there are various similarities in the amino acid sequences, overall structure, and binding capabilities between the two viruses. Predictions on how the virus can be transmitted from human to human were also included, which is crucial information for understanding exactly how this virus spreads. Such information can be utilized by scientists to better understand and predict the host cell infectivity and overall characteristics of SARS-like viruses in the future.

What were the limitations in previous studies that led them to perform this work?

  • The limitations in previous studies are mainly that they did not know the actual mechanism of this new 2019-nCoV virus. The only related virus that was studied before this work was the SARS-CoV virus and the reason that this virus was chosen to compare with this new 2019-nCoV virus was because of the similarities that both viruses share.

How did they overcome these limitations?

  • These limitations were overcome through the comparison of the new 2019-nCoV virus to what was previously known about the SARS-CoV virus. Using the already available information, predictions and models were made about 2019-nCoV virus with regards to how it is transmitted between hosts and its overall infectivity towards its hosts.

What is the main result presented in this paper?

  • The main result presented in this paper was that 2019-nCoV is comparable to the SARS-CoV virus. Based on the predicted compatibility between certain positions in the amino acid sequence of the 2019-nCoV receptor binding motif and particular hotspots on host ACE2 protein, they determined that the 2019-nCoV virus is capable of recognizing and infecting human cells, can be transmitted from human to human, and that the virus can recognize ACE2 orthologues from a variety of species.

What were the methods used in the study

  • Structural models of the SARS-CoV and 2019-nCoV viruses were created using software Coot and software PyMOL. Phylognetic trees of the different amino acid residues were also created.

Briefly state the result shown in each of the figures and tables, not just the ones you are presenting

  • Figure 1a shows that SARS-CoV has a core structure and a receptor binding motif that binds to the human ACE2 protein. Figure 1b shows that there are five amino acid residues that are essential for recognition of ACE2, cellular entry of the virus, and host range of the SARS-CoV virus. Figure 1c depicts a diagram showing that amino acids at certain positions enhance viral binding of SARS-CoV to the ACE2 protien. Figure 1d shows a model of the predicted amino acid positions that would enhance viral bonding of 2019-nCoV to the ACE2 protein.
  • Figure 2 is a phylogenetic tree showing that 2019-nCoV is ancestral to both the human SARS-CoV and bat SARS-CoV viral strains that use the ACE2 receptor.
  • Figure 3a demonstrates that the sequence alignment between SARS-CoV and 2019-nCoV have conserved residues. Figure 3b and 3c show that since SARS-CoV and 2019-nCoV share similar sequences, they most likely share the same receptor.
  • Figure 4a shows that the binding between SARS-CoV RBD and civet ACE2 occurs optimally when changes occur to residues 31 and 38. Figure 4b shows the specific bonds that can occur between SARS-CoV and civet ACE2 and that unfavorable interactions do not occur in this situation. Figure 4c shows the likely bonds that can be made between 2019-nCoV RBd and civet ACE2 and that unfavorable interactions are more likely to occur.

How do the results of this study compare to the results of previous studies

  • The results of this study confirm the results of previous studies with regards to the prediction that ACE2 is the host receptor protein that is used by the 2019-nCoV virus. This assertion was made using data gathered about the SARS-CoV virus which is very closely related to the 2019-nCoV viral strain.

What are the important implications of this work

  • The important implications of this work are that through the use of previous data on similar viral strains, it provides reliable predictions of the likely hosts, infectivity, and modes of transmission of this new 2019-nCoV virus. These predictions can be used by the scientific community to develop effective strategies to combat this virus and hopefully prevent it from causing further damage. The information provided in this study can also be used as a framework for predicting the characteristics of similar viral strains that may be introduced into society in the future.

What future directions should the authors take?

  • Possible future directions the authors should take could include further analysis into epidemic surveillance of 2019-nCoV through the use of predictive models. Also, these authors could conduct similar research on different types of viruses and make corresponding predictive models so that the scientific community can be more prepared in the future in terms of responding to a global outbreak.

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 the authors supported their conclusions very well with the data that was presented. The analysis of the particular amino acid residues and how they influenced the binding of the viruses to the particular ACE2 proteins in humans was very thorough. The predictions the authors made about the 2019-nCoV virus were based on reliable evidence gained from previous studies of related viruses. However, a possible limitation to this study is that even though the models created for 2019-nCoV were based on previous scientific data, the results are still only predictions at this time and further analysis would need to be conducted to actually confirm that the models are accurate.

Link to Presentation

Wan_Journal_Club_Presentation_CDDCMP_S2020.pdf

Scientific Conclusion

  • Through the critical analysis of this paper, I learned that the 2019-nCoV virus is very comparable to the SARS-CoV virus which has been extensively studied in the past. Even though this paper only makes predictions about the characteristics of 2019-nCoV, the models that it uses can be very useful to the scientific community with regards to the development of treatments against the virus as well as gaining an understanding of how it may affect society as a whole.

Acknowledgements

I worked with my homework partners Christina L. Dominguez and Maya A. Paniagua on 4/14/2020 via zoom to work on the group presentation.

I copied and modified the Week 11 Assignment page.

Except for what is noted above, this individual journal entry was completed by me and not copied from another source.

Dcartmel (talk) 00:40, 15 April 2020 (PDT)

References

OpenWetWare. (2020). BIOL368/S20:Week 11. Retrieved April 15, 2020 from https://openwetware.org/wiki/BIOL368/S20:Week_11.

Biology Online. (2020). Infectivity. Retrieved April 15, 2020 from https://www.biologyonline.com/dictionary/infectivity.

Oxford Dictionary of Biochemistry and Molecular Biology (2008). Orthologue. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-14381?rskey=l7rMu0&result=1.

Oxford Dictionary of Biochemistry and Molecular Biology (2008). Steric. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-18751?rskey=5KxOXQ&result=2.

A Dictionary of Plant Sciences (2019). Bifurcate. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198833338.001.0001/acref-9780198833338-e-778?rskey=KPfvLQ&result=1.

Oxford Dictionary of Biochemistry and Molecular Biology (2008). Pathogenesis. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-14812?rskey=NmgKV2&result=2.

Oxford Dictionary of Biochemistry and Molecular Biology (2008). Phylogram. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-15568?rskey=lBn8Im&result=1.

A Dictionary of Chemistry (2016). Salt Bridge. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198722823.001.0001/acref-9780198722823-e-3638?rskey=fhrL0T&result=1.

Biology Online. (2020). Putative. Retrieved April 15, 2020 from https://www.biologyonline.com/dictionary/putative.

Merriam Webster. (2020). Palm Civet. Retrieved April 15, 2020 from https://www.merriam-webster.com/dictionary/palm%20civet.

Oxford Dictionary of Biochemistry and Molecular Biology (2008). Conserved. Retrieved April 15, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-4042?rskey=GteGzv&result=1.

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). Retrieved 15, April 2020 from https://jvi.asm.org/content/94/7/e00127-20.

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