antivirals

Question 1

• Define what is meant by a virus

Answer 1

Infectious, obligate, intracellular parasites

It is absolutely dependent on the cell machinery of the host cell to replicate

Can have DNA or RNA genome

Question 2

• What size do viruses range from in diameter?

Answer 2

10nm up to a micron

Question 3

• What is the cell membrane of a non-enveloped virus made from?

Answer 3

pure protein

Question 4

• What is meant by a tegument?

- What is the central dogma?

Answer 4

A bunch of proteins in coat encapsulated within an envelope

Process by which genetic instructions are converted into a functional product
DNA converted into RNA by transcriptase
RNA used to make protein by ribosomes of the cell

Question 5

• What does it mean if a virus carries their RNA in the negative sense?

Answer 5

Complementary strand of mRNA

Before they translate genome into proteins

They copy negative sense back into complimentary copy which is positive sense to translate this into ribosomes

Question 6

• How do RNA viruses compensate for RNA genomes being shorter than DNA genomes
• What does Reverse Transcriptase do?

Answer 6

Use complex coding strategies to make more proteins than expected from small RNA genome

Makes DNA from host's nucleotides using the Virus' RNA as a template

Question 7

• Do RNA viruses & Retroviruses use their own machinery to replicate and how does this affect their mutation rate?

Answer 7

They use their own polymerase to replicate

These lack proof reading, so higher mutation rate

Question 8

• In cultured cells, why are some genes in virus’ genome lost?

Answer 8

These genes might modify the host’s immune response to give the virus a survival advantage

However, there is no immune system in cultured cells

Question 9

• What are segmented genomes and how do they affect the virus?

Answer 9

Allow an additional easy form of recombination known as, reassortment

If different strains of virus enter same host cell, the DNA can be mixed up to give a mutated virus

But also impose more difficult packaging strategies

Question 10

• Describe the stages of Virus Replication

Answer 10

Attachment - of virus’ attachment proteins to the cell membrane receptors

Insertion - of nuclear capsid with viral genome into the cell

Translation - viral genome into proteins by host cell ribosomes and machinery

Assembly - of viral proteins to form viral material

Exocytosis - virus leaves the host cell, if enveloped, then the cell membrane of host cell is used to make the lipid envelope of the virus

Question 11

• What is meant by the cytopathic effect?

- What do viral material form on cell monolayers?

Answer 11

Death of the cells, caused by the virus
Could be due to shut down of host protein synthesis or accumulation of viral proteins to form plaques

plaques

Question 12

• What is meant by virus morphology?

- Where are the lipid envelopes of viruses derived from?

Answer 12

The shape or look of a virus

From lipid membrane of the cell

Question 13

• How can you find out how many virus particles are in a particular preparation of virus?

Answer 13

Making dilutions o viral stock and putting them onto monolayers of cells

After 2/3 days, count number of plaques formed (clear holes)

Plaque Assay Method

Question 14

• What is Syncytia?

Answer 14

Viruses with surface proteins that can fuse at neutral pH often fuse cells together

Syncytia assay is also a method of finding out how may virus particles there are in a certain sample

Question 15

• What is Syncytia?

Answer 15

Viruses with surface proteins that can fuse at neutral pH often fuse cells together

Syncytia assay is also a method of finding out how may virus particles there are in a certain sample

Question 16

• How can you use PCR with an RNA genome?

Answer 16

Convert RNA to DNA

Then PCR allows the specific primers to amplify the viral DNA

Question 17

• How can serology be used to detect a virus in a patient?

Answer 17

Take blood from patient and look at the serum

To see whether there are any antibodies that are specific to that particular virus

Question 18

• Why is RT-PCR used to detect SARS CoV2?

- What is meant by the therapeutic index?

Answer 18

Because SARS CoV2 only contains RNA

Ratio between how much drug you have to use in order to control virus and how much a patient taking the drug feels the side effects

Question 19

• Give some of the ways that antiviral drugs work?

Answer 19

Some will target the viral enzymes - increased understanding of structure of viral components and enzymes can lead to rational drug design

Some act as nucleoside analogues to inhibit or interfere with nucleic acid replication but need to achieve some sense of specificity for viral polymerase

Question 20

• What do Directly Acting Antivirals target?

Answer 20

Specific viral factors (specific to virus)

Question 21

• What does a nucleoside analogue do?

Answer 21

Nucleoside analogues are synthetic, chemically modified nucleosides

They have very similar structures to nucleosides and block cellular division/viral replication  by impairment of DNA/RNA synthesis  or by inhibition of cellular or viral enzymes involved in nucleoside/tide metabolism

Question 22

• Give 4 of the nucleoside analogues used to treat viruses

Answer 22

Acyclovir - Herpes

Zidovudine - HIV

Remdesivir - Ebola

Favipiravir - Influenza

Question 23

• What is the best anti-viral agent with viral specificity?

- How does this agent work?

Answer 23

Acyclovir

Modified nucleoside incorporated into DNA
Lack of 3 prime -OH prevents phosphodiester bond formation

Question 24

• What makes this agent specific?

Answer 24

It is given to patients in un-phosphorylated form and needs to be phosphorylated to work

The thymidine kinase that forms acyclovir monophosphate is only formed by herpes virus family

Higher affinity for viral DNA polymerase than for host cell polymerase

Question 25

- What is remdesivir a nucleoside analogue of? | - What class of drugs do both Amantidine and rimantadine both belong to?

Answer 25

Adenosine Causes chain termination 3 nucleotides downstream of incorporation -twists growing molecule so it cant be extended Adamantanes

Question 26

- What is amantidine? | - How does amantidine work?

Answer 26

Cyclic amines with bulky cage-like structures only active against influenza A Sits in the middle of tetrameric ion channel - M2 ion channel H+ ions cannot enter core of particle and the virus is locked in endosomes Initiation of infection is blocked as the ribonucleoproteins of influenza can no longer leave the virus to go to the nucleus

Question 27

- What is one of the disadvantages of using amantadine?

Answer 27

Only takes single point mutation in genes coding for M2 ion channel for amantadine to no longer bind Little cost to fitness and virus still maintains virulence and is transmissable

Question 28

- Why is neuraminidase essential in the actions of influenza?

Answer 28

Cleaves bond between haemagluttinins on influenza and the sialic acid of the host cell membrane This allows the virus to continue infecting more of the host's cells

Question 29

what are the three neuraminidase inhibitors - Why was Relenza not such a successful drug as Tamiflu?

Answer 29

sialic acid, relenza, tamiflu Because the chemistry of Relenza means the virus more readily acquires resistance

Question 30

What is Baloxavir - What is meant by Biologicals?

Answer 30

anti influenza anti viral drugs targeting PA endonuclease- sub unit of RNA polymerase Largely antibodies, derived from recovered individuals or produced in the laboratory from immortalised B-cells (Passive immunotherapy)

Question 31

- Give 5 of the ways in which HIV replication can be inhibited?

Answer 31

Inhibiting entry of virus by stopping it from attaching to its receptors and co-receptors Inhibit fusion of viral and host cell membrane Targeting reverse transcriptase Target integrase (prevent DNA integrating with host DNA) Target proteases unique to viruses

Question 32

- What is an immunomodulator? - What is Dexamethasone? - What is Toculizimab?

Answer 32

a chemical agent that modifies the immune response or the functioning of the immune system Corticosteroid used for immunosuppressants Targets pro-inflammatory cytokine IL-6

Question 33

What is palivizumab

Answer 33

humanized monoclonal antibody against the pre fusion F protein of RSV

Question 34

what are the mechanisms of directly targeting antivirals against hepatitis C

Answer 34

protease inhibitors NS5B polymerase inhibitor (an RNA polymerase) non nucleoside polymerase inhibitors NS5A target

Question 35

What properties do antivirals against influenza must have

Answer 35

target unique or essential gene of function of the virus be effective against the range of influenza types and strains be easy to administer few side effects for compliancy

Question 36

how has HIV been cured before

Answer 36

Transplant bone marrow from those naturally resistant to HIUV because they have a mutation in their CRR5 receptor gene, so CRR5 is not expressed So HIV cannot enter cells