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?

 

 

 

1. 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? 

 

 

 

1. 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 make 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.

 

 

 

1. 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. 
2. What is the host membrane bilayer made of? 

 

 

1. What is the other main macromolecule that comprises the "fluid mosaic" model of a cell membrane?

 

 

1. 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?

 

 

1. 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. 
2. What is endocytosis?

 

 

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

 

 

1. What type of macromolecule is RNA?

 

 

1. 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?

 

 

1. RNA polymerases lack proofreading ability. Define proofreading ability and describe its importance in replication of DNA genomes. 
2. Why is this a critical function for human DNA polymerases? 

 

 

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

 

 

1. The positive stranded RNA serves as the template for protein synthesis. 
2. What is the process called that involves converting the RNA sequence into a sequence of amino acids?

 

 

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

 

 

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

 

 

1. 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.

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

The two important classes of macromolecules in SARS-CoV 2 are-

spike glycoproteins

ACE2 complex

 

1. 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? 

The characteristics which are used to define life are

a. must be able to respond to stimuli

b. grow over time

c. produce offspring

d. maintain a stable body temperature

e. metabolize energy

f. consist of one or more cells

g. ability to adapt to the environment

When taking SARC CoV2 into consideration, it should be noted that , they can make copies of themselves when are in contact with a cell. So, considering them inert till they come in contact with a cell in which they can replicate (viruses do not have self -generated or self - sustaining actions), they could be called alive after coming in contact with a cell.

 

1. 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 make 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.

There are 2 major types of SARC- CoV2 viruses in circulation - the L and S type. While S type is the ancestral type, the L type was found to be more prevalent. In Wuhan, after early January, the frequency of L type started to decrease. The reason being, human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and would have spread more quickly. On the other hand, the S type, which is less aggressive and evolutionary older, might have increased in relative frequency due to relatively weaker selective pressure.

 

1. What is the host membrane bilayer made of?

The lips bilayer consists of phospholipids arranged in two layers. Hence it is called bilayer. The lips are arranged with their polar hydrophilic head group facing outside and hydrophobic tail facing inside.

 

1. What is the other main macromolecule that comprises the "fluid mosaic" model of a cell membrane?

Other than phospholipids, bilayer also contains several glycoproteins, proteins and carbohydrate units. It consists of enzymes, protein receptors to receive ligands and hormones. It consists of protein channels that allow selective passage to various ions and macromolecules. It also consists of glycoproteins that face outside to work as antigens and markers outside a cell.

 

1. 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?

Recombinant protein of human angiotensin l converting enzyme (peptidyl-dipeptidase A)2

The alpha helix is a common motif in the secondary structure of proteins and is a right hand helix conformation in which every backbone N-H group hydrogen bonds to the back bone C=O group of the amino acid located three or four residues earlier along the protein sequences. Among types of local structure in proteins ,the alpha helix is the most extreme and the most predictable from sequence as well as the most prevalent

 

1. What is endocytosis?

Endocytosis is a cellular process in which substances are brought in to the cell. the material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. endocytosis includes pinocytosis (cell drinking)and phagocytosis(cell eating).it is a form of active transport.

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

A lysosome is a membrane bound organelle found in many animal cells. they are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition ,of both its membrane proteins and its luminal proteins. besides degradation of polymers ,the lysosome is involved in the various cell processes, including secretion, plasma membrane repair, cell signaling, and energy metabolism

1. What type of macromolecule is RNA?

Ribonucleic acid is a polymeric molecule essential in various biological roles in coding ,decoding, regulation and expression of genes

 

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

RNA polymerases produce complementary RNA sequence to original DNA strand. The synthesis of new RNA strand follows the principle of complementarity. So, A in the template strand pairs with U in the daughter RNA strand; G pairs with C and vice versa; T pairs with A. Now, if for any reason this pairing is mistaken and a nucleotide is paired with another nucleotide other than the assigned one, then the wrong nucleotide is removed by proofreading ability. This ensures that proper pairing between nucleotide sequences of DNA and RNA strand takes place.

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

This is a critical function for DNA polymerase as this enzyme is involved in a delicate process of DNA replication. If one daughter strand of DNA becomes defective due to improper proof reading ability of DNA polymerase, then it leads to formation of subsequent generations of defective daughter DNA strands. So, this is a critical function of the enzyme DNA polymerase.

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

Absence of this enzyme gives advantages to viruses like SARS-CoV-2 is that they can manipulate host genetic machinery more efficiently. They will gradually evolve by the production of novel proteins which gives them genetic advantage. These strains will then come out in more virulent forms which can pose serious threat to the health of the patient.

 

1. 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?

The process that converts RNA sequence to amino acid sequence of proteins is called translation.

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

The cellular "workbench" of this process is cell cytoplasm. The main part of the cell involved in this process is ribosome.

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

The sequence if RNA is converted to the sequence of amino acids with the help of tRNA. Ribosomes read the frame of RNA in sequence of three nucleotides called codons. The appropriate tRNA bearing the complementary anticodon is incorporated in the ribosome. Each codon encodes for a specific amino acid which is incorporated by ribosomes to form a chain of protein.

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

This process takes place in the cell cytoplasm just outside the nucleus. Certain ribosomes are attached to endoplasmic reticulum that carry out these functions.

 

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.

ENDOPLASMIC RETICULUM (ER)

ER is a continuous membrane system that forms a series of flattened sacs within the cytoplasm of eukaryotic cell and serve multiple functions, being important particularly in the synthesis, folding, modification and transport of proteins. in animal cell the ER usually constitutes more than half of the membranous content of the cell. functionally there are two kind of ER ,namely rough ER (ribosomes are attached) and smooth ER (ribosomes are not attached)

GOLGI APPARATUS

It is also termed as Golgi complex or Golgi body, it is a membrane bound organelle of eukaryotic cell that is made up of a series of flattened, stacked pouches called cisternae

The Golgi apparatus is responsible for transporting, modifying and packaging proteins and lipids into vesicles for delivery to targeted destination. It is located in the cytoplasm next to the ER and near the cell nucleus

Many type of cells contain only one or several Golgi apparatus, plant cells can contain hundreds

EXOCYTOSIS

Exocytosis is the process of moving materials from within a cell to the exterior of the cell. this process requires energy and is therefore a type of active transport

In exocytosis, membrane bound vesicles containing cellular molecules are transported to the cell membrane. the vesicles fuse with the cell membrane and expel their contents to the exterior of the cell

Exocytotic vesicles are formed by he Golgi apparatus, endosomes,and pre synaptic neurons. this process is important for the removel of waste, for chemical messaging between cells, and for rebuilding the cell membrane

    Sever Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. It have larger positive strand RNA genome that are 5' capped and 3' polyadenylated. during the course of infection the viral genome is incorporated with human genome and is replicated, replication followed by transcription as well as translation process, as a result viral protein is released .

The viral protein synthesis is more faster than that of the normal cells protein synthesis , this is because of the viral mRNA do not undergo post transcriptional modifications it directly undergo translation process while the human mRNA undergo post transcriptional modifications.