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NAME (in all caps) ____________________________________ Student ID ___________________ MIC 102 WS3 Page 1 of 4 Last updated: 5/26/20 WORKSHEET 3 20 points. Submit by 10:30 AM Tuesday, 6/2/20, to...

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NAME (in all caps) ____________________________________ Student ID ___________________
MIC 102 WS3 Page 1 of 4 Last updated: 5/26/20
WORKSHEET 3

20 points. Submit by 10:30 AM Tuesday, 6/2/20, to Canvas > Gradescope > Worksheet 3.

OBJECTIVES: to familiarize you with key features of the SARS-CoV-2 virus such that you can
understand—and educate others on—its replication cycle, treatment, and genome changes.

TO DO: Read and follow the instructions posted on Canvas > Assignments > Worksheet 3.


ACADEMIC INTEGRITY AFFIRMATION:

I hereby verify that the work I submit is the result of my individual effort.

FULL NAME (SIGNATURE) _________________________________________


BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an
enveloped, (+)-sense, single-strand RNA virus that causes coronavirus disease 2019
(COVID-19). The coronavirus family is named for the crown-like spikes on the outer surface
of the virus and includes viruses that infect many species of animals, including camels, cattle,
ats, and cats. The SARS-CoV-2 virus appears to have “spilled” out of bats, its primary
animal host, and into humans in December of 2019 in Wuhan, China. COVID-19 symptoms
appear 2-14 days after exposure and include fever, dry cough, shortness of
eath, chills,
muscle pain, headache, dia
hea, and loss of taste or smell. The virus spreads from person-
to-person, primarily through droplets that are released when a person coughs or sneezes,
ut also through indirect contact with secretions. It is highly contagious and spread primarily
y symptomatic individuals but also by individuals who are asymptomatic. Researchers are
working at a frantic pace to design an effective vaccine and determine whether people who
ecover from COVID-19 can be re-infected.

Coronaviruses have remarkably low mutation rates for RNA viruses. Their replicative enzyme
has low fidelity (accuracy) but they have acquired the gene for a 3’-to-5’ exonuclease (ExoN)
that removes mismatches during and after RNA synthesis.

QUESTIONS TO ANSWER:

1. (5 pts) Fill in the missing terms in the replication cycle of SARS-CoV, a virus that is very
similar to SARS-CoV-2 with respect to its replication.

A. During attachment, the SARS-CoV ___________________ [name specific viral
ligand] binds receptor molecules on the ___________________ [name specific
structure] of the host cell.
NAME (in all caps) ____________________________________ Student ID ___________________
MIC 102 WS3 Page 2 of 4 Last updated: 5/26/20
B. During penetration and uncoating, the virion enters the cell by
___________________ and then releases its genome into the cytoplasm of the
cell through ___________________ [name process].

C. During biosynthesis, the ___________________ [positive- and/or negative] –
sense genome is replicated using the viral ______________________ [name
specific enzyme] to produce ___________________ [positive- and/or negative]
– sense strands. This activity will also produce ___________________ [name
specific macromolecule] that will be translated to produce viral structural proteins.

D. As a precursor to assembly, viral surface proteins are translated in the
___________________ [name host cell compartment]. These surface proteins
will then assemble with other viral proteins and a copy of the genome.

E. During release, infectious virions leave the host cell by the process of
___________________ [name cell process].


ANTIVIRAL THERAPY

2. (2 pts) The most promising
oad-spectrum class of antiviral drugs to treat RNA virus
infections are nucleoside analogs. These are synthetic, chemically-modified bases that are
incorporated into the replicating viral genome by low-fidelity polymerases. The incorporation
of the nucleoside analog typically interferes with synthesis by the polymerase or the resultant
mutation disrupts viral genes and replication.

Unfortunately, the SARS-CoV-2 ExoN protein renders most nucleoside analogs ineffective as
a treatment against this particular RNA virus.

Explain why the proofreading activity of ExoN reduces the ability of nucleoside analogs to
inhibit viral replication.








3. (3 pts) Happily, the antiviral remdesivir was demonstrated to reduce SARS-CoV-2 replication.
Host enzymes convert it into the compound GS XXXXXXXXXXwhich, upon incorporation into the
nascent strand by the viral polymerase, terminates RNA synthesis. (continue to next page…)
NAME (in all caps) ____________________________________ Student ID ___________________
MIC 102 WS3 Page 3 of 4 Last updated: 5/26/20
A. Compare the structure of the analog GS XXXXXXXXXXbelow) to the structure of the molecule it
is mimicking, adenosine (adenine + ribose), and list three differences between them.










B. Is GS XXXXXXXXXXa competitive or non-competitive inhibitor of the viral polymerase? Briefly
explain your answer.



SCENARIO: Your neighbor is very wo
ied by a news headline claiming that the SARS-CoV-2
virus has changed and is easier to spread than the original virus. Knowing that you are in a
microbiology class, she asks you for advice on how concerned to be, and how to avoid
getting infected. You locate the original research paper and learn that: (1) researchers have
sequenced the genomes of thousands of SARS-CoV-2 viruses that were isolated from
COVID-19 cases worldwide, (2) collectively, these genomes contain multiple nucleotide
sequence variations from the early isolates from Wuhan, (3) one particular sequence variant
has a mutation in the gene for the viral ligand protein, (4) this variant is the dominant virus
spreading through Europe, and (5) the research paper was not reviewed by other scientists
efore it was uploaded to a quick-share website and reported by the press.

Consider the following to inform the advice you will give.

4. (1 pt) Which stage in viral replication is most likely to be impacted by a mutation in the viral
ligand protein?



5. (2 pt) What role does this stage (above) play in transmission (infection of a new host)?






https:
pubchem.ncbi.nlm.nih.gov/compound/ XXXXXXXXXX
https:
pubchem.ncbi.nlm.nih.gov/compound/Adenosine
NAME (in all caps) ____________________________________ Student ID ___________________
MIC 102 WS3 Page 4 of 4 Last updated: 5/26/20
6. (2 pts) Is a missense mutation guaranteed to impact the function of the protein and,
therefore, the phenotype of the virus? Briefly explain your answer.






7. (2 pts) Does the increased frequency of a particular sequence variant prove the variant has
increased transmissibility? Explain your answer.

(Consider: if an out
eak is initiated by a single infected individual, how many variants would
you expect to isolate from new cases?)









8. (1 pt) Why is it important—and standard procedure—for other experts in the field of study to
critically evaluate the methods, results, and conclusions in a manuscript before it is published
and presented to the general public as fact, particularly during an epidemic?







9. (2 pts) How concerned should your neighbor be about the reported transmissibility of the
mutated strain, and how can she avoid getting infected in light of this new data?
Answered Same Day May 31, 2021

Solution

Ankita answered on Jun 01 2021
145 Votes
WORKSHEET 3
20 points. Submit by 10:30 AM Tuesday, 6/2/20, to Canvas > Gradescope > Worksheet 3.
OBJECTIVES: to familiarize you with key features of the SARS-CoV-2 virus such that you can understand—and educate others on—its replication cycle, treatment, and genome changes.
TO DO: Read and follow the instructions posted on Canvas > Assignments > Worksheet 3.
ACADEMIC INTEGRITY AFFIRMATION:
I hereby verify that the work I submit is the result of my individual effort.
FULL NAME (SIGNATURE)     
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, (+)-sense, single-strand RNA virus that causes coronavirus disease 2019 (COVID-19). The coronavirus family is named for the crown-like spikes on the outer surface of the virus and includes viruses that infect many species of animals, including camels, cattle, bats, and cats. The SARS-CoV-2 virus appears to have “spilled” out of bats, its primary animal host, and into humans in December of 2019 in Wuhan, China. COVID-19 symptoms appear 2-14 days after exposure and include fever, dry cough, shortness of
eath, chills, muscle pain, headache, dia
hea, and loss of taste or smell. The virus spreads from person- to-person, primarily through droplets that are released when a person coughs or sneezes, but also through indirect contact with secretions. It is highly contagious and spread primarily by symptomatic individuals but also by individuals who are asymptomatic. Researchers are working at a frantic pace to design an effective vaccine and determine whether people who recover from COVID-19 can be re-infected.
Coronaviruses have remarkably low mutation rates for RNA viruses. Their replicative enzyme has low fidelity (accuracy) but they have acquired the gene for a 3’-to-5’ exonuclease (ExoN) that removes mismatches during and after RNA synthesis.
QUESTIONS TO ANSWER:
1. (5 pts) Fill in the missing terms in the replication cycle of SARS-CoV, a virus that is very similar to SARS-CoV-2 with respect to its replication.
A. During attachment, the SARS-CoV S protein    [name specific viral
ligand] binds receptor molecules on the Angiotensin-converting enzyme 2    [name specific structure] of the host cell.
(
NAME (in

all

caps)

__

_ Student

ID


)
(
MIC 102 WS3
) (
Page
1
of 4
) (
Last updated: 5/26/20
)
B. During penetration and uncoating, the virion enters the cell by
Receptor-mediated endocytosis     and then releases its genome into the cytoplasm of the
cell through
degradation of viral or host enzymes or dissociation     _ [name process].
C. During biosynthesis, the positive    [positive- and/or negative] – sense genome is replicated using the viral replicase            [name specific enzyme] to produce negative        [positive- and/or negative]
– sense strands. This activity will also produce mRNA     specific macromolecule] that will be translated to...
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