www.BioInteractive.org
Updated July 2021
Page 1 of 14
Biology of SARS-CoV-2
Click & Learn
Educator Materials
OVERVIEW
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, called COVID-19, has affected millions of people worldwide.
Biology of
SARS-CoV-2 is a four-part animation series that explores the biology of the virus, including the structure
of coronaviruses like SARS-CoV-2, how they infect humans and replicate inside cells, how the viruses
evolve, methods used to detect active and past SARS-CoV-2 infections, and how different types of
vaccinations for SARS-CoV-2 prevent disease.
The accompanying “Student Worksheets” incorporate concepts and information from the animations.
The “Version 1” worksheet was written by a high school educator and is appropriate for general high
school biology students. The “Version 2” worksheet was written by a college educator and is appropriate
for AP/IB Biology and undergraduate students. The worksheets can be edited or combined based on
your learning goals.
This document contains multiple resources for using the animations with students, including the
following (click links to go directly to each section):
• specific pause points
for the animations with content summaries and questions
• general discussion points for the animations
• answer keys for the “Version 1” and “Version 2” worksheets
• references that provide more background on the science in the animations and worksheets
Additional information related to pedagogy and implementation can be found on this resource’s
webpage, including suggested audience, estimated time, and curriculum connections.
KEY CONCEPTS
• Viruses with an RNA genome have their RNA translated into proteins by an infected cell.
• Viruses hijack cellular machinery to make viral proteins, replicate, and spread to other cells.
• Mutations are random and can have positive, negative, or no effects on viruses.
• Mutations in the viral genome can be used to track how a virus is spreading through populations.
• Diagnostic tests for viral infections can detect viral RNA, viral antigens, or antibodies the body has
produced in response to the virus.
• Vaccines protect from future disease by delivering antigens that trigger an immune response
w
ithout causing an actual infection.
• Vaccines can deliver a weakened or inactivated form of the virus, antigen proteins, or genetic
instructions such as DNA or mRNA.
STUDENT
LEARNING TARGETS
• Identify structural components of SARS-CoV-2.
• Describe the steps in the SARS-CoV-2 replication cycle.
• Explain how mutations arise in the viral genome.
• Describe how a virus can change over time due to mutations.
• Outline several different ways to detect a viral infection.
• Describe how different types of vaccines expose the immune system to specific antigens.
• Explain how antigens stimulate a natural immune response, including the concepts of antibodies
and immune memory.
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 2 of 14
Click & Learn
Educator Materials
PRIOR KNOWLEDGE
Before watching the animations, students should have a basic understanding of:
• what genetic mutations are
• the flow of genetic information from DNA to RNA to proteins
• the immune system
Before completing the “Version 1” worksheet, students should have a basic understanding of:
• the definition of a genome as the genetic makeup of an organism or virus
• the function of the viral envelope
• how vaccines work
Before completing the “Version 2” worksheet, students should have a basic understanding of:
• the ways in which cell types differ, including in their cell surface proteins
• the process of DNA replication
• terms associated with DNA and RNA replication, such as template, polymerase, and elongation
• analyzing and interpreting DNA sequence data, including how differences in DNA sequences can be
used to track evolution
PAUSE
POINTS
The animations may be viewed in their entirety or paused at specific points to review content with
students. The table below lists suggested pause points, indicating the beginning and end times in
minutes for each of the four animations.
For Infection:
Begin
End
Content Description
Review Questions
0:00
0:39
● Severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) is a
m
ember of the coronavirus family
that causes a disease called COVID-19.
● When a person gets a nasal swab to see
if they have been infected by SARS-
CoV-2, it is typically called a “COVID-19
test.” What would be a more accura
te
name for this test?
0:40
0:50
● Coronaviruses can be found in many
animals, including humans.
● Coronavirus diseases in humans range
from mild to severe.
● What types of animals carry
coronaviruses?
● Does SARS-CoV-2 cause the common
cold?
0:51
1:13
● The structure of a coronavirus
includes an RNA genome, a
m
embrane called the envelope, and
spike proteins (called “protein spikes”
in the animation).
● What type of genome do coronaviruses
have? How does that differ from the
human genome?
● Why is this family of viruses called
coronaviruses?
1:14
1:35
● After entering the human body, a
virus gets into a cell and releases its
genome inside the cell.
● How does SARS-CoV-2 enter the body?
● Once inside the body, how does the
virus gain entry into a cell?
1:36
2:08
● The virus genome is translated,
replicated, and packaged inside the
human cell.
● Why do you think the virus is able to
use the human cell’s ribosomes but not
the cell’s polymerase?
2:09
2:35
● The virus spreads to new cells and
individuals, prompting an immune
response and symptoms.
● Can a person with no symptoms spread
SARS-CoV-2?
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 3 of 14
Click & Learn
Educator Materials
For Evolution:
Begin
End
Content Description
Review Questions
0:00
0:43
● The SARS-CoV-2 genome is a single-
stranded RNA of about 30,000
nucleotides that encodes fewer than
30 proteins.
● Does the length of the virus’s genome
or the number of proteins it encodes
surprise you? Why or why not?
0:44
1:24
● SARS-CoV-2 replicates its genome by
producing complementary template
R
NAs, which are used to make new
RNAs that match the virus’s genome
.
● Mutations occur randomly during the
g
enome replication process.
● Mutations occur when nucleotides are
added, left out, or substituted fo
r a
different nucleotide.
● What are three ways in which
nucleotides may be changed, resulting
in a mutation?
1:25
2:21
● Mutations that provide a selective
advantage help a virus spread through
a population.
● Mutations that provide a selective
disadvantage hinder a virus’s ability to
spread.
● Neutral mutations have no effect on a
virus’s ability to spread.
● Would a mutation that becomes more
common in a population over time be
most likely to provide a selectiv
e
ad
vantage, provide a selective
disadvantage, or have no effect?
● Why might a mutation that has a
positive effect on the virus have a
negative effect on humans?
2:22
2:47
● Tracking mutations in viruses is
helpful for understanding viral spread
and developing treatments for v
iral
diseases.
● Why is tracking virus evolution so
important?
For Detection:
Begin
End
Content Description
Review Questions
0:00
1:03
● Available tests for SARS-CoV-2 assess
whether a patient has an active
infection or a past infection.
● One test for an active infection is the
RT-PCR test, which detects viral RNA.
● Which part of the virus does the RT-
PCR test detect?
● Is the RT-PCR test effective while the
patient is currently infected or afte
r
they have recovered?
1:04
1:21
● Another test for an active infection is
the antigen test, which detects viral
proteins.
● Which part of the virus does the
antigen test detect?
● What are antigens?
1:22
1:49
● One test for a past infection is the
antibody test, which detects whether
the immune system has produced
antibodies to fight off the virus.
● What does the antibody test detect?
● What are antibodies?
1:50
2:22
● Each of the three types of tests has
strengths and weaknesses and can be
used to find out different information
about an infection.
● Based on the graph at 2:03, when
might it be more appropriate to get an
antibody test than an RT-PCR o
r
a
ntigen test?
● What is a false negative?
For Vaccination:
Begin
End
Content Description
Review Questions
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 4 of 14
Click & Learn
Educator Materials
0:00
0:56
● The immune response is how the
immune system responds to a viral
i
nfection. It includes the production of
many cell types that help destroy th
e
v
irus.
● One cell type, B cells, produces
antibodies that bind to protein
antigens on the surface of the virus.
● Antibodies help prevent the virus
from entering cells and target it fo
r
destruction.
● What is the immune response?
● What are antigens and antibodies?
Which comes from the virus, and which
is made by the body?
● How do antibodies help protect us
from viruses?
0:57
1:25
● The immune response converts some
B cells into memory B cells, which can
stay in the body for years and protec
t
t
he body from infection.
● Without memory B cells, it takes more
time to produce enough antibodies to
fight a virus. In the meantime, th
e
virus may cause serious disease.
● When someone says their body
“remembers” a particular virus, what
does that mean? How is that memory
acquired?
1:26
3:29
● Vaccines deliver antigens to trigger an
immune response without causing
d
isease.
● Vaccines for SARS-CoV-2 deliver
antigens in three main forms: inactive
whole virus, antigen proteins, and
genetic instructions (mRNA or DNA).
● How does a vaccine help prevent
disease?
● Why don’t vaccines cause the same
symptoms as the virus?
● Why do you think vaccine developers
might select one vaccine type over
another?
3:30
4:05
● While the vaccines themselves are
eliminated from the body, the
memory B cells produced by the
immune response to the antigens can
last for years, providing protection.
● Additional doses, called booster shots,
may be needed to keep antibody
levels high.
● New vaccines may be needed as the
virus mutates.
● Some SARS-CoV-2 vaccines require two
doses. Why?
4:06
4:30
● Vaccinated people limit the virus’s
ability to spread within a population.
● Herd immunity describes the point at
which a population has enough
vaccinated people to protect the full
population. Do you think every person
within the population needs to be
vaccinated to achieve herd immunity?
Why or why not?
DISCUSSION POINTS
For Infection:
● After students watch this animation, assess their understanding of how a coronavirus replicates. You
may want to introduce the terms “positive-sense” and “negative-sense” when talking about RNA,
then ask students to explain the replication of SARS-CoV-2 using these terms.
o If necessary, explain that the genome of SARS-CoV-2 is a positive-sense, single-stranded RNA,
which means that it can be used as mRNA in the cell. From that “mRNA,” the cell’s ribosomes
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 5 of 14
Click & Learn
Educator Materials
translate viral RNA polymerase, which is necessary to replicate the viral genome. The
polymerase transcribes the virus’s positive-sense genome into a negative-sense template
strand, which is used to make more copies of the genome. This replication cycle is illustrated
within the coronavirus section of the Virus Explorer
Click & Learn.
• Consider having students do the Virus Explorer Click & Learn to learn more about the structure and
replication of viruses. The Click & Learn includes a description of “sense” and has a detailed diagram
of the coronavirus replication cycle that students can explore and discuss.
For Evolution:
• Have students consider news headlines alerting that SARS-CoV-2 is mutating. Ask whether
mutations in the virus will always be bad for humans or not.
o One point that you may want to emphasize is that most mutations are neutral, and mutations
that provide a strong selective advantage or disadvantage are relatively rare. This is not
explicitly mentioned in the animation.
For Detection:
• You may want to extend students’ understanding of the RT-PCR test by discussing how it works.
o In particular, the virus’s RNA genome must be transcribed into DNA before it can be sequenced.
First, the enzyme reverse transcriptase (from retroviruses) is used to transcribe the RNA into
DNA. Then, the polymerase chain reaction (PCR) is used to make many copies of the DNA fo
r
s
equencing.
• Consider discussing pros, cons, and students’ questions about the three tests (RT-PCR test, antigen
test, and antibody test) in the animation.
o The FDA’s Coronavirus Testing Basics
page provides more information on these tests, including
how samples are taken, how long it takes to get results, and potential caveats.
o SARS-CoV-2 antibody tests in particular currently have many open questions. (How long does it
take antibodies for SARS-CoV-2 to be produced? How long do these antibodies last afte
r
i
nfection? Do these antibodies protect a person from future infections? How many peopl
e
w
ould need antibodies for the population to be protected?)
You could ask students to consider why these tests might still be useful to perform, even if
we don’t know the answers to all the questions above. Students could also discuss potential
negative consequences to performing these tests without more information.
• Consider connecting the concepts in this animation to SARS-CoV-2 testing recommendations that
s
tudents may have heard about.
o For example, when a person comes in close contact with someone who has tested positive for
SARS-CoV-2, the Centers for Disease Control (CDC)
have recommended that the person
quarantine for 14 days, regardless of whether they have tested negative on the RT-PCR test or if
t
hey have any symptoms. Ask students to discuss the reasoning behind this recommendation.
(Can a person be infected without symptoms? How might a person test negative and still be
infected?)
For Vaccination:
• You may want to clarify that the immune response and vaccines can protect the body from many
pathogens, not just viruses. For example, there are also vaccines for diseases caused by bacteria,
such as tetanus, diphtheria, and pertussis (whooping cough).
• You may want to clarify that B cells and antibodies are only part of the immune response. Other
immune cells, such as T cells, play major roles as well. Like B cells, T cells can also become memory
cells that help protect the body from future infections.
• Students may know the vaccines by their trade names rather than by their mechanisms. Here are
examples of each vaccine type and companies that are developing them:
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 6 of 14
Click & Learn
Educator Materials
o Inactive whole virus: Sinovac, Sinopharm
o Protein antigen: Novavax
o DNA: CanSino, AstraZeneca, and Johnson & Johnson
o mRNA: Pfizer, Moderna
• For the “Version 2” worksheet, consider relating student answers to Question 20 to the three tests
(RT-PCR test, antigen test, and antibody test) discussed in the Detection video. Then discuss how
these tests can avoid false positives from certain vaccines.
o The RT-PCR test does not detect the genetic instructions (DNA or mRNA) vaccines because i
t
d
etects a different region of the viral genome than the region that encodes the spike protein
(which is delivered by these vaccines).
To understand the RT-PCR test, students may need additional background on PCR. For a
brief summary of how PCR works, consider showing the Polymerase Chain Reaction
animation. This animation does not show the first step for the RT-PCR test: reverse
t
ranscription (RT), in which the viral RNA is converted to DNA.
You may want to discuss the role of primers with students. As shown in the PCR animation,
primers are short DNA sequences designed to bind a specific region of target DNA. In the RT-
PCR test for SARS-CoV-2, the target region typically does not vary too much (or else the
primers may not bind, causing false negatives) but varies enough to allow SARS-CoV-2 to b
e
d
istinguished from other coronaviruses. A common target for primers is the nucleocapsid-
encoding region of the viral genome; for more details on the structure of coronaviruses,
refer to Virus Explorer
.
o Antigen tests typically detect the nucleocapsid protein, which is not present in either the
a
ntigen protein vaccines or the genetic instructions (DNA and mRNA) vaccines. Therefore, thes
e
v
accines would not be detected by the antigen tests.
o Many antibody tests detect antibodies for the spike protein, which are produced in response to
all the vaccines in the animation. However, antibody tests are not relevant to Question 20
because they should not be used to detect active viral infections, as antibodies remain long after
t
he virus has been cleared.
o Whether these tests detect the inactive whole virus vaccine varies. The virus is typically
chemically inactivated with chemicals such as formalin and
β-propiolactone. These chemicals
can modify proteins, nucleotides, or both. Depending on the chemical used, certain tests may
give false positives for the inactive whole virus vaccine and others may not.
TEACHING
TIPS
• Consider conducting a formative assessment prior to watching the animations. Some ideas are as
follows:
o Before class, make a list of common misconceptions about SARS-CoV-2 or COVID-19 that you
have become aware of in your community or seen on social media. Include several factu
al
s
tatements in the list as well.
■ Invite students to discuss which of these statements are accurate and which are not. Record
their decisions.
■ Revisit the list after viewing the animations. Ask students if they have changed their earlier
decisions about the accuracy of the statements.
o Ask students to make a list of what they know about coronavirus infection, evolution, and
detection. This can be done individually or in pairs.
■ Ask students to share one or two items from their lists with the class. Reinforce that, at this
point, all ideas are to be accepted.
■ After viewing the animations, invite students to address misconceptions they had about
SARS-CoV-2 and COVID-19. Ask students to discuss where some of these misconceptions
may have originated.
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 7 of 14
Click & Learn
Educator Materials
• Consider discussing with students how they could become better informed about COVID-19 and
other real-world issues and less prone to misconceptions.
o For example, students may have seen news articles making false or misleading claims about
COVID-19. Students could analyze these articles using the “Evaluating Science in the News”
activity, in which they evaluate a science news article to determine whether it is trustworthy.
• Some examples in the worksheets are based on real research studies. You may wish to have
students explore the original studies and data in more depth. A full list of references can be found at
the end of this document. In particular:
o In the “Version 1” worksheet:
■ Question 3, which describes SARS-CoV-2’s ability to bind to cell receptors, is based on
Wrapp et al. (2020)
.
■ Question 9, which describes a large deletion in some SARS-CoV-2 viruses, is based on
Holland et al. (2020)
.
o In the “Version 2” worksheet:
■ Questions 6 and 7, which discuss how the drug remdesivir could potentially treat SARS-CoV-
2 infections, are based on Gordon et al. (2020)
.
■ Questions 10–14, which compare SARS-CoV-2 viruses in different states, use real sequence
data from GenBank
. GenBank links for all of these sequences are provided in the
“References” at the end of this document.
STUDENT WORKSHEETS
There are two “Student Worksheets” that can be used to accompany the animations. “Version 1” was
developed by a high school educator, and “Version 2” was developed by a college educator. Both
worksheets were designed as learning assessments that probe students’ understanding of the key
concepts addressed in the animations. They can be used to assess students’ understanding after
watching the animations or to guide students as they watch the animations. You may modify the
worksheets as needed (e.g., reducing the number of questions, adding explanations of vocabulary for
English Language Learners, etc.) in order to better fit your learning objectives and your students’ needs.
ANSWER
KEY (VERSION 1)
PART 1: Infection
1. Explain how the terms COVID-19, SARS-CoV-2, and coronavirus mean different things.
COVID-19 is a disease, and SARS-CoV-2 is the virus that causes the disease. SARS-CoV-2 is a specific
type of coronavirus. Coronaviruses are a family of viruses that infect humans and other animals.
2. The diagram below represents a SARS-CoV-2 virus. In the table below the diagram, identify each o
f
th
e labeled structures. Write one or two sentences describing the role of each structure in the
virus’s replication process.
Label
Structure
Role in replication
1
RNA
genome
The RNA genome carries the virus’s genetic information, including genes for
proteins that the virus needs to make more copies of itself.
2
Protein
spikes
The protein spikes attach to specific proteins on the surface of a cell. This allows
the virus to enter the cell, release its RNA genome, and use the cell’s machinery
to make more copies of itself.
3
Envelope
membrane
The envelope gives the virus its shape and protects the virus’s genome so that it
can be replicated. (Since the envelope is made from cell membranes, it helps
protect the virus from the immune system. You may want to explain this to
students since it is not explicitly explained in the animation.)
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 8 of 14
Click & Learn
Educator Materials
3. Scientists discovered that SARS-CoV-2 is 10 to 20 times more likely to bind to these receptors than
the other coronavirus was. Predict how this increased chance of binding has affected SARS-CoV-2’s
ability to replicate.
A coronavirus must bind to receptors on a cell in order to enter that cell. Since SARS-CoV-2 is more
likely to bind to the receptors, it is more likely to enter cells and produce copies of itself. So, this
increased chance of binding probably improves SARS-CoV-2’s ability to replicate.
4. Each of the following statements describes a step in the replication of SARS-CoV-2. These steps are
listed in random order. Read through the steps and, in the spaces provided below, list them in the
order they occur in the human body.
a. The virus releases its RNA genome into the cell.
b. Viral RNA polymerase helps transcribe more copies of the virus’s RNA.
c. The virus binds to a receptor on a human cell’s membrane.
d. New viruses travel to the cell membrane of the infected cell and are released outside the cell.
e. The virus’s RNA is translated into proteins by the cell’s ribosomes.
Correct order: c, a, e, b, d
5. As shown in the animation, SARS-CoV-2 uses the ribosomes inside human cells to translate its RNA
into viral proteins. According to the animation, what is one of the viral proteins made by the
ribosomes, and how does that protein help SARS-CoV-2 make more copies of itself?
One of the viral proteins made by the ribosomes is viral RNA polymerase, which is necessary to
replicate the virus’s genome. The polymerase makes copies of the virus’s RNA, which are used to
make new viral genomes and proteins that combine to make new viruses.
PART 2: Evolution
6. The SARS-CoV-2 virus has an RNA genome made of 30,000 nucleotides. Identify the four different
types of nucleotides found in the SARS-CoV-2 genome.
A, U, C, and G. (A stands for the base adenine, U for uracil, C for cytosine, and G for guanine. The
names of these bases are often used as the names of the nucleotides, though they
are not
technically the same.)
7. Could these mutations make the virus more deadly to humans? Support your answer in one or two
sentences.
Some mutations could make the virus more deadly, if they help the virus replicate or infect cells
more easily. However, other mutations might make the virus less deadly or have no effect.
8. Predict how the frequency of viruses with this deletion will change in the population over time. Use
evidence to support your answer.
This large deletion would most likely reduce or eliminate the protein’s function, making it harder
for the virus to escape the immune system. If so, viruses with this deletion would have a selective
disadvantage (since they are more likely to be destroyed by the immune system) and would thus
become less common in the population over time.
(It is possible, although very unlikely with a deletion of this size, that the deletion could make the
protein more effective at helping the virus escape the immune system. If so, the viruses with the
deletion would have a selective advantage and would become more common in the population
over time.)
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 9 of 14
Click & Learn
Educator Materials
9. How could sequencing many SARS-CoV-2 genomes be used to track how the virus has changed over
time due to mutations?
You could compare the genome sequences of SARS-CoV-2 samples taken from people in different
locations over time. If there are variations among the genomes — such as more, fewer, or
different nucleotides — you could track when and where these variations are present and
determine when related mutations had occurred.
PART 3: Detection
10. Imagine you are planning to visit a family member who is a nursing home resident. The nursing
home requires that all visitors test negative for an active SARS-CoV-2 infection no more than two weeks
before the visit. Which of the two tests shown above would you choose, or what other information
would you want to learn before choosing? Use evidence from the table to support your answer.
Student answers will vary; be open to a range of logical responses. If students prioritize speed, they
may want to get the antigen test. If they prioritize accuracy and want fewer false negatives (e.g.,
because they are concerned about the risk of infecting a family member), they may want to get the
RT-PCR test. Students may also discuss other information they’d want to know before choosing. This
could include things like the availability of the tests, where they can get tested, how much each test
would cost with/without health insurance, whether there are other tests they could get, etc.
11. In addition to the tests described above, people can also get tested for the presence of SARS-CoV-2
antibodies. Explain how an individual could test negative for an active SARS-CoV-2 infection and
positive for SARS-CoV-2 antibodies.
The individual could test negative for an active infection and positive for antibodies if they were
infected in the
past and have since recovered. Since they have recovered, they will no longer have
the virus. But they will still have antibodies from having fought the virus before.
P
ART 4: Vaccination
12. The animation describes the following types of SARS-CoV-2 vaccines. Briefly summarize how each
type of vaccine triggers an immune response. (Hint: Remember that the immune system responds
specifically to antigens.)
a. Inactive whole virus
The inactive virus in the vaccine contains antigens that trigger an immune response.
b. Antigen proteins
The antigen proteins (e.g., spike proteins) in the vaccine
trigger an immune response directly.
c. mRNA (genetic instructions)
The mRNA in the vaccine is translated into antigen proteins, which trigger an immune
response.
d. DNA (genetic instructions)
The DNA in the vaccine is transcribed into mRNA. The mRNA is then translated into antigen
proteins, which trigger an immune response.
13. As shown in the animation, some SARS-CoV-2 vaccines deliver mRNA for the spike protein. Mark
each of the following statements about this mRNA as either true or false.
Once the mRNA has entered a person’s cells, it…
True (T) or False (F)
…is translated into spike proteins.
T
…is integrated into the cells’ DNA.
F
…helps trigger the production of B cells.
T
…is eventually eliminated from the body.
T
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 10 of 14
Click & Learn
Educator Materials
14. Why would an unvaccinated person probably need more time to recover from a SARS-CoV-2 infection
than a vaccinated person would?
Assuming that the unvaccinated person hasn’t had a SARS-CoV-2 infection before, they wouldn’t have
memory B cells or antibodies that can quickly protect them from the virus. This person would need
more time for their body to produce enough B cells and antibodies to fight the virus, and they might
experience more serious disease in the meantime.
15. Why might people need another SARS-CoV-2 vaccination if the SARS-CoV-2 virus mutates?Vaccines
help the body produce B cells and antibodies that target specific antigens on the virus. If the
virus’s antigens change due to mutations, these B cells/antibodies may no longer be able to
target the virus. You may need a new vaccine, one with antigens from the mutated virus, to
produce new B cells/antibodies that target the mutated virus.
A
NSWER
KEY (VERSION 2)
PART 1: Infection
1. Describe the shape and location of SARS-CoV-2’s protein spikes.
The animation shows that the protein spikes are shaped like clubs and stick out from the virus’s
surface (envelope).
2. What is the function of the spike protein?
The spike proteins bind to specific proteins on the surface of a cell, allowing the virus to enter the
cell.
3. Predict how mutations in the gene that encodes the spike protein might affect the types of cells the
virus infects.
Mutations in the gene that encodes the spike protein could change the amino acids encoded and
therefore the shape and/or chemical properties of the spike protein. These changes may increase
or decrease the spike protein’s ability to bind to certain cell surface proteins. Different cell types
have different cell surface proteins, so changes in the spike protein could affect which cell types
the virus can bind to and thus infect.
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.
Student models will vary. An example is shown below.
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 11 of 14
Click & Learn
Educator Materials
5. List the similarities and differences between cellular DNA replication and the RNA genome
replication process used by coronaviruses.
Student answers will vary depending on what they already know about DNA replication (which is
not covered in the animation). Example responses are shown below.
Similarities
● occurs in cells
● uses the nucleotides A, C, and G
● replicates nucleic acids from “template” strands using complementary base pairing
Differences
DNA replication for cells
RNA genome replication for viruses
● replicates a double-stranded molecule (DNA)
● uses T (thymine)
● uses the enzyme DNA polymerase
● replicates a single-stranded molecule (RNA)
● uses U (uracil)
● uses the enzyme RNA polymerase
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?
In Figure 1, remdesivir appears most structurally similar to the nucleotide A.
7. Propose a hypothesis about how remdesivir might inhibit the virus’s replication process.
Student hypotheses may vary, but should be stated as testable, falsifiable statements
.
E
xample 1: Remdesivir prevents the new RNA from fully elongating
.
E
xample 2: Remdesivir introduces mutations into the new RNA.
PART 2: Evolution
8. When SARS-CoV-2 replicates in cells, mutations can occur in the virus’s genome. Explain how
a
m
utation (insertion, deletion, or substitution) in one of the virus’s genes might affect a protein it
encodes
.
Mutations may have no effect on the protein encoded by the gene, or they may cause changes in
the protein’s amino acids. These amino acid changes may affect the structure, size, and function of
the protein.
9. What impacts might mutations have on the transmission of the virus?
Mutations that help the virus replicate or infect cells could increase the virus’s transmission
.
M
utations that make the virus less effective at replication or infection could decrease it
s
t
ransmission. Other mutations may not affect the virus’s transmission at all.
10. Which of the following types of mutations is represented in Table 1?
a. Substitutions (correct answer)
b. insertions
c. deletions
11. At which stage of viral infection did these mutations most likely occur?
They probably occurred during the virus’s genome replication process, which is prone to errors.
12. Fill in the last column of Table 1 to indicate the number of nucleotide differences between the virus
from Washington and the viruses from other states.
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 12 of 14
Click & Learn
Educator Materials
Position in the sequence alignment
Number of
differences
State
1059
3037
14408
18060
23403
25563
28144
Washington
C
C
C
T
A
G
C
–
Utah
C
T
T
C
G
T
T
6
Colorado
C
C
C
C
A
G
T
2
Kansas
C
T
T
C
G
G
T
5
California
T
T
T
C
G
T
T
7
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?
Mutations accumulate over time. So, the viruses with more sequence differences from the
W
ashington virus probably arose later. (For reference, the actual collection dates for thes
e
s
amples were as follows. Washington: January 19, 2020; Colorado: March 7, 2020; Kansas: March
10, 2020; Utah: April 13, 2020; California: April 30, 2020.)
PART 3: Detection
15. List the three types of molecules detected by the tests in the animation.
Viral RNA, viral antigens (proteins), and antibodies
16. Imagine that three individuals get all three tests. Propose a possible explanation for each individual’s
test results, as shown in the following table.
Individual
RT-PCR
test
Antigen
test
Antibody
test
Explanation
1
Positive
Positive
Negative
This individual’s RT-PCR and antigen tests are positive
because they have an active infection. Their antibody test is
negative because their immune system hasn’t made
antibodies against the virus yet.
2
Positive
Negative
Negative
This individual’s RT-PCR test is positive because they have an
active infection. Their antigen test should also be positive but
produced a false negative in this case. Their antibody test is
negative because their immune system hasn’t made
antibodies against the virus yet.
(Consider discussing with students why the antigen test is
more likely to produce a false negative than the RT-PCR test.
The RT-PCR test is much more sensitive than the antigen test
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 13 of 14
Click & Learn
Educator Materials
because it amplifies viral RNA, which makes the virus easier
to detect. The antigen test detects only the antigens/proteins
that are present, so the virus must be replicating at high
levels before it can be detected by the antigen test.)
3
Negativ
e
Negative
Positive
This individual’s RT-PCR and antigen tests are negative
because they had a past infection and recovered, so the virus
is no longer in their body. Their antibody test is positive
because their body still has the antibodies that were made to
fight the virus.
PART 4: Vaccination
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 th
e
b
ody generates spike proteins for each vaccine type.
a. DNA vaccines
DNA delivered by the vaccine is transcribed into mRNA, which is translated into protein.
b. mRNA vaccines
mRNA delivered by the vaccine is directly translated into protein.
18. Do the genetic instructions (DNA and mRNA) vaccines contain the virus’s full genome? If not, wha
t
r
egion(s) of the genome do they contain?
These vaccines just contain the region that encodes the spike protein.
19. Do the antigen protein vaccines contain all the proteins in the virus? If not, which protein(s) do they
contain?
These vaccines just contain the spike protein.
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
It depends on how the virus is inactivated, but there may not be a good test in this
case.
Antigen proteins
You could use an antigen test that detects a different viral protein than the spike
protein. Or you could use an RT-PCR test that detects any part of the virus’s RNA
genome, since no viral RNA is delivered by this type of vaccine.
Genetic instructions
(DNA or mRNA)
You could use an RT-PCR test that detects a different part of the virus’s genome than
the region that encodes the spike protein.
REFERENCES
Astuti, Indwiani, Ysrafil. “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview
of viral structure and host response.” Diabetes & Metabolic Syndrome: Clinical Research & Reviews
14, 4 (2020): 407–412. https://doi.org/10.1016/j.dsx.2020.04.020
.
Bar-On, Yinon M., Avi Flamholz, Rob Phillips, and Ron Milo. “Science Forum: SARS-CoV-2 (COVID-19) by
the numbers.” eLife 9 (2020): e57309. https://doi.org/10.7554/elife.57309
.
Biology of SARS-CoV-2
www.BioInteractive.org
Updated July 2021
Page 14 of 14
Click & Learn
Educator Materials
GenBank (for California SARS-CoV-2 isolate sequence [accession number MT460135.1]; accessed
September 14, 2020). https://www.ncbi.nlm.nih.gov/nuccore/MT460135.1
.
GenBank (for Colorado SARS-CoV-2 isolate sequence [accession number MT512430.1]; accessed
September 14, 2020). https://www.ncbi.nlm.nih.gov/nuccore/MT512430.1
.
GenBank (for Kansas SARS-CoV-2 isolate sequence [accession number MT512442.1]; accessed
September 14, 2020). https://www.ncbi.nlm.nih.gov/nuccore/MT512442.1
.
GenBank (for Utah SARS-CoV-2 isolate sequence [accession number MT536965.1]; accessed September
14, 2020). https://www.ncbi.nlm.nih.gov/nuccore/MT536965.1
.
GenBank (for Washington SARS-CoV-2 isolate sequence [accession number MN985325.1]; accessed
September 14, 2020). https://www.ncbi.nlm.nih.gov/nuccore/MN985325.1
.
Gordon, Calvin J., Egor P. Tchesnokov, Emma Woolner, Jason K. Perry, Joy Y. Feng, Danielle P. Porter,
and Matthias Götte. “Remdesivir Is a Direct-Acting Antiviral That Inhibits RNA-Dependent RNA
Polymerase from Severe Acute Respiratory Syndrome Coronavirus 2 with High Potency.” Journal of
Biological Chemistry 295, 20 (2020): 6785–6797. https://doi.org/10.1074/jbc.ra120.013679
.
Holland, LaRinda A., Emily A. Kaelin, Rabia Maqsood, Bereket Estifanos, Lily I. Wu, Arvind Varsani, Rolf U.
Halden, et al. “An 81-Nucleotide Deletion in SARS-CoV-2 ORF7a Identified from Sentinel Surveillance
in Arizona (January to March 2020).” Journal of Virology 94, 14 (2020): 1–3.
https://doi.org/10.1128/JVI.00711-20
.
Lan, Jun, Jiwan Ge, Jinfang Yu, Sisi Shan, Huan Zhou, Shilong Fan, Qi Zhang, et al. “Structure of the SARS-
CoV-2 Spike Receptor-Binding Domain Bound to the ACE2 Receptor.” Nature 581, 7807 (2020): 215–
220. https://doi.org/10.1038/s41586-020-2180-5
.
U.S. Food & Drug Administration. “Coronavirus Testing Basics.” Last modified July 16, 2020.
https://www.fda.gov/consumers/consumer-updates/coronavirus-testing-basics
.
Wrapp, Daniel, Nianshuang Wang, Kizzmekia S. Corbett, Jory A. Goldsmith, Ching-Lin Hsieh, Olubukola
Abiona, Barney S. Graham, Jason S. McLellan. “Cryo-EM structure of the 2019-nCoV spike in the
prefusion conformation.” Science 367, 6483 (2020): 1260–1263.
https://doi.org/10.1126/science.abb2507
.
CREDITS
“Version 1” worksheet written by Mary Colvard, Cobleskill-Richmondville High School, NY (retired)
“Version 2” worksheet written by Holly Basta, Rocky Mountain College, MT
Edited by Bridget Conneely, Laura Bonetta, Esther Shyu, HHMI; Jason Crean
, Saint Xavier University, IL
Illustrations by Heather MacDonald