BIOL368/S19 week3

Purpose

The purpose of this assignment is to be able to understand research, analyze, and evaluate it.

Terms Definitions

1. Dipeptide: An organic compound formed when two amino acids are joined by a peptide bond.
2. Threonine: A colorless crystalline amino acid found in protein; occurs in the hydrolysates of certain proteins; an essential component of human nutrition.
3. Albeit: although
4. Aspartate: a nonessential amino acid that plays a critical part of the enzyme in the liver that transfers nitrogen-containing amino groups, either in building new proteins and amino acids or in breaking down proteins and amino acids for energy and detoxifying the nitrogen in the form of urea
5. Angiotensin:a 60-kDa polypeptide hormone originating in the liver. It is converted from angiotensin I to angiotensin II by the angiotensin converting enzyme.
6. Residues: a small amount of something that remains after the main part has gone or been taken or used.
7. Tyrosine: one of the 20 common amino acids with an aromatic and carboxylic acid as the R-group
8. Reiterative: marked by iteration. iterative. repetitious, repetitive - characterized by repetition; "repetitive movement"
9. 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.
10. Surveillance: monitoring of behavior, activities, or information for the purpose of information gathering, influencing, managing or directing

Article Outline

Abstract:

• The paper analyzes the potential receptor usage by 2019-nCoV, based on the knowledge about SARS-CoV which was an outbreak in 2002, and the newly released sequence of 2019-nCoV.
• 2019-nCoV has a similar sequence to t SARS-CoV which suggests that 2019-nCoV uses the human enzyme ACE2 as its receptor just like SARS-CoV do.
  • Gln493 in 2019-nCoV RBM showed interaction with ACE2
• Asn501 is not ideal for binding the human ACE2 however it’s compatible and therefore gives 2019-nCoV the ability to transmit between humans.
• 2019-nCoV is originated from bat showing that 2019-nCoV recognizes ACE2 from a variety of animal species.
• The analysis that the paper has given information about how the receptors are used and how 2019-nCoV enters the cell, how the cell is infected, and the origin of 2019-nCoV which would help with finding ways to prevent 2019-nCoV and to treat it.

Introduction:

• This paper was written early in the pandemic where there were only human 500 cases.
• Symptoms of 2019-nCoV are like SARS-CoV which happened in 2002-2003 and caused 8000 human infections and 800 deaths.
• SARS-CoV was transmitted from palm civets to humans.
• Coronaviruses are single-stranded enveloped RNA viruses
  • 2019-nCoV and SARS-CoV both belong to the β-genus.
• Spike proteins mediate coronaviruses entry into host cells
• 2019-nCoV has a similar sequence to t SARS-CoV which suggests that 2019-nCoV uses the human enzyme ACE2 as its receptor just like SARS-CoV do.
  • Gln493 in 2019-nCoV RBM showed interaction with ACE2
• Based on knowledge known about SARS-CoV and the similarities it has to 2019-nCoV RBD, the sequence of 2019-nCoV RBD (receptor binding domain) was used to provide information about the receptor and host range related to 2019-nCoV.

Material and Methods:

• Structural analysis:
  • Software Coot used to introduce mutations to structural models
  • Structural figures prepared by Software PyMOL
• Phylogenetic analysis:
  • Consensus radial phylograms generated in Geneious using the Jukes-Cantor genetic distance model (the neighbor-joining build method, and no outgroup, with 100 bootstrap replicates)
  • Phylograms rendered for publication in Adobe Illustrator CC 2020.
• Sequence alignment:
  • Clustal Omega used for protein sequencing.

Results:

• The similarities between 2019-nCoV and SARS-CoV sequence suggest that they share the same receptor (ACE2) however, 2019-nCoV RBM unlike SARS-CoV doesn’t have any deletion or insertion.
• Most of the evidence showed that ACE2 is the receptor for 2019-nCoV.
• Results showed that Gln493 in 2019-nCoV RBD is compatible with hot spot 31 in ACE2.
• 2019-nCoV level of recognition to human ACE2 shows that It’s capable to transmit from human to human.
• Receptor binding domains of 2019-nCoV are all favorable of binding to ACE2 suggesting that 2019-nCoV infects ACE2 of human and therefore infect them.
• In terms of 2019-nCoV RBD interactions with ACE2 from animals other than human, it’s showed that residue 31 of civet became thionine and can no longer form a bond with Glu35 and residue 38 becomes glutamate and forms a bridge with Lys353.
• 2019-nCoV most likely uses civet ACE2 as its receptor, even though it shows that 2019-nCoV RBD has evolved adaptively for civet ACE2 binding.
• 2019-nCoV likely does not use mouse or rat ACE2 as its receptor.
• 2019-nCoV RBD recognizes ACE2 from a wide number of species including humans, pigs, and bats, however, it doesn't recognize ACE2 from mouse and rat.

Discussion:

• Like previous publications, this research paper showed that 2019-nCoV uses ACE2 as a host receptor.
• Prior knowledge of SARS-CoV and ACE2 allowed for this research to be done.
• 2019-nCoV uses human ACE2 less efficiently than human SARS-CoV (year 2002) however 2019-nCoV uses human ACE2 more efficiently than human SARS-CoV (year 2003)
• When 2019-nCoV is diagnosed in patients, mutations at the 501 position should be taken into consideration

It’s determined that bats are most likely the source of 2019-nCoV.

• • Just like Bats are the source of SARS-CoV
• In terms of SARS-CoV, some RBM residues adapted to Civet ACE2
  • For 2019-nCoV there's no evidence of RBM adaptation to Civet ACE2
• Both SARS-CoV and 2019-nCoV don’t replicate in mice and rats.
• The Animal models that could be used for 2019-nCoV include 2019-nCoV
• It's determined that Wild animals along with Bats in Wuhan, China should be screened because they caused both 2019-nCoV and SARS-CoV
• Further research should be done to have a complete understanding of the reasons for 2019-nCoV and SARS-CoV inactivity in certain organisms.
• The long research of SARS-Co confirmed that receptor recognition of SARS-Co is the reason for it Transmation between human and across species.
• This study gives insight about 2019-nCoV to help find a way to battle 2019-nCoV.

Evaluation

• The paper is well written and clearly shows the similarities between 2019-nCoV and SARS-CoV.
• It gives a good insight into how 2019-nCoV functions.
• The author should consider the spread of 2019-nCoV in comparison to SARS-CoV in future research as 2019-nCoV is currently a pandemic and has an effect on society and the world far more than SARS-CoV as it spread more and based on that the author should research the reason that 2019-nCoV had such a huge spread and how we can control it.

Scientific Conclusion

The paper discussed how the SARS-CoV-2 virus acts similarly in the human body as 2019-nCoV does in terms of the bond it makes and spreading between humans and from other animals to human. Finally, the results showed that the two viruses are very similar, giving leads on how to treat the 2019-nCoV virus and the origin of it.

Acknowledgments

• My Homework Partner Kam Taghizadeh worked with me in analyzing the figures.

References

• OpenWetWare. (2020). BIOL368/F20:Week 3. Retrieved September 23, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_3
• Learn Biology Online. (2020, February 18). Retrieved September 23, 2020, from https://www.biologyonline.com
• 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

Except for what is noted above, this individual journal entry was completed by me and not copied from another source Falghane (talk) 22:47, 23 September 2020 (PDT)