Kam Taghizadeh Week 3

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Purpose

  • The purpose of this week's journal assignment is to utilize skills to interpret journal articles, outline them, and decipher what the included figures entail.

10 Unknown Vocabulary Terms and Definitions

  1. 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)
  2. MERS: "Middle East Respiratory Syndrome (MERS) is viral respiratory illness that is new to humans. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries, including the United States."(cdc.gov)
  3. ACE: "Angiotensin-converting enzyme"(Biology Online)
  4. Angiotensin: "A family of oligopeptides associated with increased blood pressure, mainly by causing vasoconstriction."(Biology Online)
  5. Salt Bridge: "Salt bridges in proteins are bonds between oppositely charged residues that are sufficiently close to each other to experience electrostatic attraction."(Wiley Online Library)
  6. Transmission: "1. (Science: microbiology, physiology) A passage or transfer, as of a disease from one individual to another or of neutral impulses from one neuron to another."(Biology Online)
  7. Pathogenesis: "The origin and development of disease."(Biology Online)
  8. Phylogram: "A tree-like diagram showing the degree of relationship of different TAXA." (Medical Dictionary)
  9. Residue: "Any of the monomers comprising a polymer, or any of the parts that integrate to make up a larger molecule"(Biology Online)
  10. Receptor: "Receptors are proteins, usually cell surface receptors, which bind to ligands and cause responses in the immune system, including cytokine receptors, growth factor receptors and Fc receptor."(Sino Biological)

Outline of the article: "Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus"

Abstract

  • Symptoms of Covid 19 are very similar to SARS-CoV
  • Since the outbreak of SARS-CoV in 2002, a lot of research has been conducted on an atomic level
    • Interactions on the atomic scale were found between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2)
  • This research has helped immensely for the analyses of Covid 19
    • First, it was revealed that the sequence of 2019-nCoV RBD and its receptor-binding motif (RBM) that binds to ACE2 are highly similar to SARS-CoV's
      • This suggests that 2019-nCoV uses ACE2 as its receptor
    • Second, it was also revealed that certain residues in 2019-nCoV RBM interact in a favorable manner with human ACE2
      • This is evidence for its capacity to infect human cells
    • Third, it was revealed that other particular residues have capacity for binding with ACE2 although they were not ideal
      • This suggests human-human transmission
    • Fourth, while it is known through phylogeny that 2019-nCoV is of bat origin, it also has an affinity for ACE2 in other animals
      • This reveals that covid 19 can have other hosts as well

Introduction

  • Covid 19 has caused at least 17 deaths and 500 confirmed cases in Wuhan, China
    • There are also other confirmed cases in other countries such as the US
  • Symptoms resemble severe acute respiratory syndrome coronavirus (SARS-CoV)
    • Symptoms include:acute respiratory syndrome
  • SARS-CoV emerged in 2002, leading to 8,000 cases and remerged in 2003, leading to 4 cases
    • It is said that SARS-CoV was transmitted from palm civets to humans in an animal market in Southern China
  • Covid-19 also emerged from an animal market in China, the animal is unknown however
  • It has been revealed from previous research that the Receptor Binding Domain (RBD) of SARS-CoV binds to its host receptor angiotensin-converting enzyme 2 (ACE2)
  • It has also been revealed from previous research that the SARS-CoV RBD contains a receptor-binding motif (RBM), and this is where ACE2 binds
  • Researchers have found five residues in RBD with high bonding affinity to human ACE2
    • When all of these residues were combined and placed into one RBD, it bound with human ACE2 very efficiently
  • Figure 1A:Shows the Receptor Binding Domain (RBD) of SARS-CoV binding to its host receptor angiotensin-converting enzyme 2 (ACE2)
  • Figure 1B:Shows the differences in the five important residues with high bonding affinity to human ACE2
  • Figure 1C:Shows the interaction between optimized human SARS-CoV RBD and human ACE2
  • Figure 1D:Shows the interaction between human 2019-nCoV RBD and human ACE2
  • An important goal for this study is to be able to predict receptor usage for future SARS-CoV or SARS-like viral strains based on their spike protein sequences

Results

  • The percent similarity between the spikes of 2019-nCoV and SARS-CoV:76% to 78%
  • The percent similarity between the RBD of 2019-nCoV and SARS-CoV:73% to 76%
  • The percent similarity between the RBM of 2019-nCoV and SARS-CoV: 50% to 53%
    • MERS=CoV and HKU4 (bat MERS-like coronavirus)have lower similarity in their spikes but still bind to the same receptor
      • This suggests that 2019-nCoV and SARS-CoV could share the same receptor, ACE2
    • Furthermore, 2019-nCoV does not have any insertions or deletions except for one loop away from the ACE2 receptor
    • Also, out of the 14 ACE2 residues, 9 are completely conserved and 4 are partly conserved among 2019-nCoV and SARS-CoV from human, civet, and bat
  • Figure 2:Shows the spike phylogeny of β-genus lineage b coronaviruses
  • Figure 3A:Shows the alignment between 2019-nCoV and SARS-CoV RBDs
  • Figure 3B:Shows the similarities in sequences between 2019-nCoV and SARS-CoV
  • Figure 3B:Shows the similarities in sequences between the MERS-CoV and HKU4 virus
  • Residue 493 is glutamine, and it corresponds to residue 479 in SARS-CoV
    • Residue 479 is near a binding hotspot Lys31 on human ACE2
      • Hot spot 31 has a salt bridge between Lys31 and Glu35 in a hydrophobic environment
      • In Civet, residue 479 is a lysine, which causes steric and electrostatic interference with hot spot 31
      • In human SARS-CoV RBD, residue 479 is asparagine
  • Residue 501 in 2019-nCoV RBD is asparagine, corresponds to residue 487 in SARS-CoV
    • Based on previous research, residue 487 located near virus binding hot spot Lys353 in SARS-CoV
      • Hot spot 353 has a salt bridge between Lys353 and Asp38 embedded in a hydrophobic environment
    • In civet SARS-CoV RBD (year 2002), residue 487 is a serine and does not provide support for hot spot 353
  • Residues 455, 486, and 494 in 2019-nCov: leucine, phenylalanine, and serine
    • Correspond to residues 442, 472, and 480 in SARS-CoV, respectively
    • They do not play as big of a role as residues 493 and 501
    • Show evidence that 2019-nCoV recognizes ACE2
  • The interactions of 2019-nCoV of ACE2 receptors in other species
    • It is likely that 2019-nCoV RBD recognizes ACE2 from pigs, ferrets, cats, orangutans, monkeys, and humans due to their ACE2 molecules being identical or similar in the critical virus-binding residues
  • Figure 4A:Shows the five residues in ACE2 from different species
  • Figure 4B:Shows the interaction between the designed SARS-CoV RBD and civet ACE2
  • Figure 4C:Interaction between Human 2019-nCoV and civet ACE2

Discussion

  • The analysis conducted allows for confidence in the fact that 2019-nCoV uses ACE2 as its host receptor
    • Two other publications also note this
    • Human 2019-nCoV uses ACE2 less adequately than human SARS-CoV (year 2002) but more adequately than human SARS-CoV (year 2003)
  • An alarming discovery is that if there is one N501T mutation, then 2019-nCoV RBD binding affinity for ACE2 could increase dramatically
  • 2019-nCoV has most likely evolved from bats, given from phylogenetic analysis
    • No mutations were found for the binding to Civet ACE2
      • It is possible that civets had transmitted 2019-nCoV to humans before 2019-nCoV could adapt to civet ACE2

Materials and Methods

  • Structural analysis- PyMOL: Protein structure analysis
  • Phylogenetic analysis- Geneious Prime
  • Sequence analysis- Clustal Omega

Questions from Week 3 Assignment

  1. What were the goals and results of previous studies that led them to perform this work?
    • The results from previous studies include the sequence of SARS-CoV, along with the interaction between SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2). This allowed for the atomic analysis of Covid-19, which is seen to be very similar in that it also binds to ACE2.
  2. What future directions should the authors take?
    • A future direction that these authors should take is to now look at a greater database, as they have only looked at cases from Wuhan. It is important that they do this so they can have more well rounded results
  3. Give a critical evaluation of how well you think the authors supported their conclusions with the data they showed.
    • This paper gave a lot of interesting information regarding Covid 19 and its relationship to SARS. To make it better however, it would be nice to have a more detailed materials and methods section. This way, other researchers would be able to replicate their findings.
  4. Are there any limitations or major flaws in the paper?
    • I did not see any limitations other than the fact that everything was computer generated, and did not have real time lab work to show.
  5. Implications?
    • This research can help policy makers with directing society how to move forward during this pandemic
    • With this much knowledge regarding SARS-CoV and Covid-19, a vaccine or could be produced to target ACE2

Scientific Conclusion

  • This week's assignment taught us to break down the scientific article into its outline, so we can truly grasp what every section is talking about. It is very important as biologists to be able to decipher papers such as this one, to inform the public regarding the pandemic right now. By defining key terms, we are able to broaden our vocabulary and make the papers to come easier to read and analyze.

Acknowledgements

  1. I referenced OpenWebWare syntax from BIOL368/F20 week 1 page.
  2. I referenced OpenWebWare instructions from BIOL368/F20 week 3 page.
  3. I referenced Purdue Owl for instructions regarding APA formatting.
  4. I referenced the article "Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus" for this week's journal entry.
  5. I collaborated with my partner Fatima Alghanem through face time to analyze our assigned figures.

References

  1. Biology online.(2020). Ace. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/ace
  2. Biology online.(2020).Angiotensin. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/angiotensin
  3. Sino Biological.(2020). Receptor. Retrieved September 23, 2020, from https://www.sinobiological.com/research/receptors/what-are-receptors
  4. Wiley Online Library.(2004).Salt Bridges. Retrieved September 23, 2020, from https://onlinelibrary.wiley.com/doi/abs/10.1002/jmr.657
  5. Centers for Disease Control and Prevention.(2020). Middle East Respiratory Syndrome (MERS). Retrieved September 24, 2020, from https://www.cdc.gov/coronavirus/mers/index.html
  6. OpenWetWare.(2020). BIOL368/F20:Week 1. Retrieved September 23, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_1
  7. OpenWetWare.(2020). BIOL368/F20:Week 3. Retrieved September 23, 2020, from https://openwetware.org/wiki/BIOL368/F20:Week_3
  8. Dictionary.com.(2020).Palm Civet. Retrieved September 23, 2020, from https://www.dictionary.com/browse/palm-civet?s=t
  9. Biology online.(2020).Pathogenesis.Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/pathogenesis
  10. Medical Dictionary.(2020).Phylogram. Retrieved September 24, 2020, from https://medical-dictionary.thefreedictionary.com/phylogram
  11. Biology online.(2020).Residue. Retrieved September 24, 2020, from https://www.biologyonline.com/dictionary/residue
  12. The Purdue Owl.(2018).Citation Chart. Retrieved September 23, 2020, https://owl.purdue.edu/owl/research_and_citation/using_research/documents/20180719CitationChart.pdf
  13. Biology online.(2020).Transmission. Retrieved September 23, 2020, from https://www.biologyonline.com/dictionary/transmission

"Except for what is noted above, this individual journal entry was completed by me and not copied from another source" Kam Taghizadeh (talk) 21:39, 23 September 2020 (PDT)

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