INTRODUCTION

SARS-CoV-2 is a virus that, starting in 2020, has caused the largest global pandemic in recent
history. The disease caused by this virus, COVID-19, has affected millions of people worldwide.
In this activity, you’ll watch the animation series Biology of SARS-CoV-2 and answer related
questions to check your understanding. The concepts you’ll learn will help you better
understand COVID-19 and coronaviruses, as well as other viruses and outbreaks in the past,
present, and future.

PROCEDURE
There are four animations in this series. Watch each animation, pausing between animations to
answer the questions below in the spaces provided.

PART 1: Infection
Watch the first animation, Infection, which shows how SARS-CoV-2 infects and replicates inside
human cells.
1. Describe the shape and location of SARS-CoV-2’s protein spikes.
- As described per the video, the protein spikes are shaped like clubs and sticks. They stick
out of the virus’s outer body.
2. What is the function of the spike protein
- The spikes are used to latch onto hosting cells and infect them with their virus.
3. Predict how mutations in the gene that encodes the spike protein might affect the types of
cells the virus infects
- Mutations in the spike proteins alter the transferring of the virus from the latched spiked to
the host. Additionally, differently encoded spike proteins will be attracted to differing kinds of
cells.
4. Draw and label a model that shows how complementary base-pairing is used to create a new
strand of DNA during cellular DNA replication. Your model should include the following labels:
template strand, new strand, base pair, and DNA polymerase.
- DNA polymerase transcribes the viruses RNA, making more copies that are then translated
into proteins. This process creates virus proteins, as well as virus genomes. These two factors
combine to form a new virus that is packaged into an envelope that is formed by the cells
membranes.
5. List the similarities and differences between cellular DNA replication and the RNA genome
replication process used by coronaviruses.

Simil arities
 - In both of these scenarios, mutations
can occur that alters the viruses’ abilities
based on the mutation. For example: some
viruses may spread better or worse than a
standard coronavirus due to the mutation.
- Although slight mutations can occur
during the replication process, most of the
viruses produced by the original will share
more similarities than not.

Diffe rences

Cellular DNA replication: RNA genome replication for

- Exact copies of the existing cell are
made – there is no room for error or
mutations.
coronaviruses
- When copies are made, mutations can
occur. Mutations entail slight change in the
virus that can alter its performance. This
includes infection rate and lifespan.

- Requires building blocks called - Somewhat like genetics; a series of four

nucleotides. letters that can be interchanged with another.
- Around 30,000 genomes per multiplied Depending on the sequence of letters, what
copy. the virus can do can completely change.

Remdesivir is an antiviral drug with potential to treat SARS-CoV-2 infections. It is a broad-

spectrum antiviral, meaning it has activity against many different viruses. Remdesivir can be
incorporated into a new RNA chain as a virus replicate and can interfere with the viral replication
machinery.
Figure 1. A representation of remdesivir and the viral replication machinery for SARS-CoV-2.

6. Figure 1 shows that remdesivir “mimics” an important component of RNA replication. Which
component of RNA replication has a structure similar to that of remdesivir?

 Mimics an RNA nucleotide building block.

7. Propose a hypothesis about how remdesivir might inhibit the virus’s replication process.

 This is done by mimicking its building blocks.

PART 2: Evolution
Watch the second animation, Evolution, which
shows how SARS-CoV-2 and other viruses may
change over time due to mutations.
8. When SARS-CoV-2 replicates in cells, mutations can occur in the virus’s genome. Explain
how a mutation (insertion, deletion, or substitution) in one of the virus’s genes might affect a
protein it encodes.

 A mutation can affect the overall performance of the virus. For example: a slight
mutation in the protein spike can drastically alter the virus’ spreading capabilities.
9. What impacts might mutations have on the transmission of the virus?
The earliest SARS-CoV-2 infections in the United States were detected in the state of
Washington in January 2020. Scientists have since sequenced SARS-CoV-2 genomes from
infected individuals throughout the country.
Table 1 shows some sequence data for the gene that encodes the spike protein, which was
sequenced from
SARS-CoV-2 viruses collected in different states. (The last column of the table is left blank for
you to fill in later.) The gene’s sequence in the virus collected from Washington early in the
pandemic is between 99% and 100% identical to that of viruses collected from Utah, Colorado,
Kansas, and California later on. However, some mutations have occurred at specific locations in
the gene over time.
Table 1. Data on the sequences of spike proteins from SARS-CoV-2 viruses collected in different states
from January to May 2020. Note that during the process of amplifying and sequencing the viral RNA
genomes, the RNA is converted to DNA. Data from GenBank.

Numbe
r of
Position in the sequence alignment differen
 State 1059 3037 14408 18060 23403 25563 28144 ces

Washin C C C T A G C N/A
gton

Utah C T T C G T T Six

Colorad C C C C A G T Two
o

Kansas C T T C G G T Five

Californi T T T C G T T Seven
a

10. Which of the following types of mutations is represented in Table 1? A.

a. substitutions
b. Insertions
c. deletions
11. At which stage of viral infection did these mutations most likely occur?

 The stage of a viral infection where mutations occur is known as synthesis. During
synthesis, the virus multiplies, giving new and unique attributes to its new self.
12. Fill in the last column of Table 1 to indicate number of nucleotide differences between the
virus from Washington and the viruses from other states.
13. Knowing that the virus from Washington probably arose first, make a list below predicting
the order, from first to last, in which the viruses from these states arose.
a. Washington
b. Colorado
c. Kansas
d. Utah
e. California
14. Why did you select this order?

 This order of states corresponds to the number of differences the states had to
Washington. From least to greatest, the state with the least differences to Washington is
Colorado - hence its second.
PART 3: Detection
Watch the third animation, Detection, which shows several ways to test whether someone has
been infected by the SARS-CoV-2 virus.
15. List the three types of molecules detected by the tests in the mutation

 Viral RNA, Viral Antigens, and Antibodies.

16. Imagine that three individuals get all three tests. Propose a possible explanation for
everyone's test results, as shown in the following table.

Individual RT-PCR Antigen test Antibody test Explanation

test

1 Positive Positive Negative This series of

tests shows that
although this
patient has
tested positive,
this is their first
time getting the
virus.
2 Positive Negative Negative This series of
test represents
that although the
patient has
testes positive
from a swab
test, their
immune system
has not yet
recognized the
virus as present
- could be a
false positive.
They have not
had the virus
before.
3 Negative Negative Positive This patient
does not have
the virus, as
know genome
can be found,
their immune
system has not
recognized a
virus, and the
patient has
never contracted
 the virus.

PART 4: Vaccination
Watch the fourth and final animation, Vaccination, which shows how different types of
vaccinations for SARSCoV-2 prevent disease.
17. Antigen protein vaccines deliver the spike protein directly into the body. The DNA and
mRNA vaccines, however, make the cells of the body generate the spike protein. Briefly
describe how the body generates spike proteins for each vaccine type.
a. DNA vaccines: administered into the body through a inactivated adenovirus, which is then
transformed from DNA to mRNA once in the body. From there, the mRNA is transformed into
spike proteins that fight the infection.
b. mRNA vaccines: the spike proteins antigens of the virus are placed into the body through
an artificial membrane. Once in, the antigens cause an immune response in your body which
gives memory B cells a virus to remember.
18. Do the genetic instructions (DNA and mRNA) vaccines contain the virus’s full genome? If
not, what region(s) of the genome do they contain.

 Some types of vaccines carry the virus’s full, inactive genome. On the other hand, some
only carry the spike protein of the virus; depends on the vaccine that is administered.
19. Do the antigen protein vaccines contain all the proteins in the virus? If not, which protein(s)
do they contain?

 No, antigen protein vaccines do not contain all of the proteins originally found in the
virus, as that would cause problems for the patient. The only protein that is used is the
spike protein antigen, which then triggers an immune response.
20. For each vaccine type in the animation, propose a test that could detect an active viral
infection without false positives from that vaccine. (Hint: It may help to review the tests for active
infections in the Detection animation. Note that there may not be a good test in every case.)

Vaccine type Proposed test without false positives

Inactive whole virus RT-PCR Test

Antigen proteins Antigen Test

Genetic instructions (DNA or mRNA) Antibody Test