Understanding SARS-CoV-2 and COVID-19

Macromolecules and the structure of SARS-CoV-2

Late 2019 and early 2020 saw the appearance and spread of a novel coronavirus SARS-CoV-2 of zoonotic (animal) origin, spreading from Wuhan, Hubei province, China, around the globe, resulting in a disease termed COVID-19 (for coronavirus disease 2019). Consider this scenario as you work to synthesize many concepts we have covered into a larger story.

1.Like other viruses, SARS-CoV-2 in essence consists of what two important classes of macromolecules of the four that we studied?

2.List characteristics that can be used to define life, and discuss which if any apply to this coronavirus. Considering its structure, would you define SARS-CoV-2 as alive? 

3.In early March, it was reported that two main strains of SARS-CoV-2 had been identified, termed S and L, with the S type being the less virulent ancestral form representing about 30% of prevalence and the more virulent L type having descended from the S type and representing about 70%  of prevalence. However, the prevalence of the more virulent L type seems to have decreased after early January, and it is thought that this resulted from human intervention against this more virulent strain; meanwhile, the milder S form seems to have increased in relative frequency. Explain these findings in terms of evolution by natural selection and the relative fitness of these two strains.

4.The SARS-CoV-2 is an enveloped virus, meaning it is surrounded by a bilayer of membrane that it acquires as it exits the host cell. 

a.What is the host membrane bilayer made of? 

b.What is the other main macromolecule that comprises the “fluid mosaic” model of a cell membrane?

5.To gain entry, spikes of the SARS-CoV-2 bind to angiotensin-converting enzyme 2 (ACE2) found in epithelial cells especially of the respiratory and oral passageways. As such, these cells are susceptible to infection by SARS-CoV-2. ACE2 is a protein consisting of multiple alpha-helices that is embedded in, and spans, the membrane. What is this type of protein called, and what structure do the alpha helices represent?

6.Following binding of spike proteins to ACE2, SARS-CoV-2 likely gains entry into the cell either via fusion of its envelope with the cell membrane, or via endocytosis. If the latter, the virus must escape the endosome before fusion with the cellular lysosome. Once inside the cytoplasm, the virus unpackages and its positive stranded RNA genome is released. 

a.What is endocytosis?

b.What is a lysosome, and what is its importance in the cell?

c.What type of macromolecule is RNA?

7.The virus hijacks the cell, and RNA polymerases produce the complement to the positive stranded RNA genome. We can call these strands negative strands, and they then serve as templates for RNA polymerases to produce their complement. How does the sequence of these strands, the complement to the negative strands, compare with the original viral genome?

8.RNA polymerases lack proofreading ability. Define proofreading ability and describe its importance in replication of DNA genomes. 

a.Why is this a critical function for human DNA polymerases? 

b.What advantage might its absence give RNA viruses like SARS-CoV-2?

9.The positive stranded RNA serves as the template for protein synthesis. 

a.What is the process called that involves converting the RNA sequence into a sequence of amino acids?

b.What is the cellular “workbench” of this process, and what is this “workbench” composed of (i.e., what structure accomplishes protein synthesis)?

c.How is the sequence of RNA converted into a sequence of amino acids?

d.Where does this process take place in the human cell?

1.Following protein synthesis, RNA genome and proteins assemble to form virus particles that then bud into the endoplasmic reticulum (ER) lumen and then on to the Golgi apparatus. Next, they are transported via Golgi vesicles to the cell membrane, where they are released via exocytosis. Define ER, Golgi apparatus, and exocytosis, and explain how this process undertaken by these viruses is comparable to processes regularly used by the cell.