Coronavirus 'Variants of Concern ' Activity

What virus is responsible for the COVID-19 pandemic?

The COVID-19 disease is caused by a virus called SARS-Cov-2. It belongs to a family of viruses known as coronaviruses.
The  coronavirus is a tiny sphere about 100 nm in diameter with protrusions on its surface called spike proteins.

Figure 1: 3D medical animation showing the structure of a coronavirus (https://www.scientificanimations.com/coronavirus-symptoms-and-prevention...)


How does the coronavirus infect humans?

The coronavirus is essentially a protective shell containing genetic code. Inside the shell is a long strand of RNA containing about 30,000 bases.
The coronavirus needs a human cell to produce more viruses. First, the virus RNA must enter the cell, and then it commandeers the cell's own machinery to make more viruses.
The model below shows how the coronavirus RNA (green) enters the human cell (pink) through a channel produced by the spike proteins at the interface.
The virus has about 80 spike proteins on its surface which are about 20 nm in length.
Scientists are very interested in the spike proteins as changes in the spike protein molecules can affect how easily humans are infected by the virus, the severity of the illness, whether a person will catch COVID-19 again, the reliability of diagnostic tests and importantly the long term effectiveness of vaccines.

 

How has coronavirus become more infectious over time?

When a virus replicates it doesn’t always manage to produce an exact copy of itself. A change in the genetic sequence is called a mutation. Mutations are common in viruses, scientists reckon that coronavirus acquires around two single-letter mutations in its RNA each month. Viruses with new mutations are called variants.
Occasionally, these random changes give the virus some advantage that makes it easier to spread between people. Over time the variants that are transmitted easier dominate. In May 2021 the World Health Organization (WHO) assigned Greek letters to these key variants of concern.

In September 2020, a new variant of the coronavirus called the UK or Alpha variant was detected. It appears to be about twice as infectious than the original virus. This resulted in a second wave of infection in the UK.
Subsequently, the Delta variant, first detected in India, spread across the globe. This is about twice as infective as the Alpha variant and resulted in a third wave of infection in the UK.
The increase in the transmission rate of the virus has been linked to changes (mutations) in the amino acids in the spike protein sequences.
The location of the mutations in the Alpha and Delta variants are highlighted on a coronavirus spike protein in the model below.

 

Exercise 1: View the mutations in the spike protein sequence of the alpha and delta variants

A team of researchers at the University of Dundee have developed a software called Jalview that scientists can use to study proteins, RNA and DNA.
It reads files directly from public biological databases and views sequences, 3D structures and evolutionary trees.

CLICK this link to launch Jalview and compare the original coronavirus spike protein sequence with those of the alpha and delta variants

JalviewJS may take a few seconds to open and load the sequence in the adjacent web browser window.

In the Jalview viewer, the coronavirus spike protein sequence originating from China can be compared to the Alpha (UK) and Delta (India) sequences. Each letter represents different amino acids in the protein chain.
Feel free to play! For example, place the mouse cursor on the sequence and move the mouse across the different amino acids. Move the scroll bars at the side of the window to view its full length.
Look for differences in the amino acid letters in the sequence columns.
Q. Can you spot the differences between the sequences?
The 'Conservation' row below the sequences may help.

Figure: The original SARS-Cov-2 spike protein sequence aligned with the Alpha and Delta variants

 


Exercise 2: View the sequence of the coronavirus spike protein alongside its 3D structure

CLICK this link to view the coronavirus sequence and its 3D structure

JalviewJS may take a few seconds to open and load the sequence in the adjacent web browser window.
Feel free to play! For example, rotate the 3D structure by placing the mouse cursor on the structure and then move the mouse. Or place the mouse cursor on the sequence and move the mouse across the different bases. Look at the status bar in the lower left-hand side of the alignment window as this contains extra information.


Exercise 3: View the entire coronavirus genome

CLICK this link to view the coronavirus genome

The genome is made up of 4 different bases with letters A (adenine), C (cytosine), G (guanine ) or U (uracil).
In the Jalview viewer, place the mouse cursor on a letter and look at the status bar (lower left-hand corner of the alignment window), it will tell you the name of the nucleotide bases and its ID number.
Scroll to the end of the genome using the mouse wheel or the scroll bar (on the right-hand side of the alignment window).
Q. What is the last letter?
Click on the last letter C in the sequence, look at the status bar in the lower left-hand corner of the alignment window.
Q. How many bases are in the coronavirus genome?

Figure: The SARS-Cov-2 coronavirus genome