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POM > antivirals > Flashcards

antivirals Flashcards

1
Q
  • Define what is meant by a virus
A

Infectious, obligate, intracellular parasites

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

Can have DNA or RNA genome
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2
Q
  • What size do viruses range from in diameter?
A

10nm up to a micron

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3
Q
  • What is the cell membrane of a non-enveloped virus made from?
A

pure protein

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4
Q
  • What is meant by a tegument?

- What is the central dogma?

A

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
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5
Q
  • What does it mean if a virus carries their RNA in the negative sense?
A

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
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6
Q
  • How do RNA viruses compensate for RNA genomes being shorter than DNA genomes
  • What does Reverse Transcriptase do?
A

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
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7
Q
  • Do RNA viruses & Retroviruses use their own machinery to replicate and how does this affect their mutation rate?
A

They use their own polymerase to replicate

These lack proof reading, so higher mutation rate
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8
Q
  • In cultured cells, why are some genes in virus’ genome lost?
A

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
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9
Q
  • What are segmented genomes and how do they affect the virus?
A

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
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10
Q
  • Describe the stages of Virus Replication
A

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
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11
Q
  • What is meant by the cytopathic effect?

- What do viral material form on cell monolayers?

A

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

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12
Q
  • What is meant by virus morphology?

- Where are the lipid envelopes of viruses derived from?

A

The shape or look of a virus

From lipid membrane of the cell

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13
Q
  • How can you find out how many virus particles are in a particular preparation of virus?
A

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
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14
Q
  • What is Syncytia?
A

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
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15
Q
  • What is Syncytia?
A

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
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16
Q
  • How can you use PCR with an RNA genome?
A

Convert RNA to DNA

Then PCR allows the specific primers to amplify the viral DNA
17
Q
  • How can serology be used to detect a virus in a patient?
A

Take blood from patient and look at the serum

To see whether there are any antibodies that are specific to that particular virus
18
Q
  • Why is RT-PCR used to detect SARS CoV2?

- What is meant by the therapeutic index?

A

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
19
Q
  • Give some of the ways that antiviral drugs work?
A

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
20
Q
  • What do Directly Acting Antivirals target?
A

Specific viral factors (specific to virus)

21
Q
  • What does a nucleoside analogue do?
A

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
22
Q
  • Give 4 of the nucleoside analogues used to treat viruses
A

Acyclovir - Herpes

Zidovudine - HIV

Remdesivir - Ebola

Favipiravir - Influenza
23
Q
  • What is the best anti-viral agent with viral specificity?

- How does this agent work?

A

Acyclovir

Modified nucleoside incorporated into DNA
Lack of 3 prime -OH prevents phosphodiester bond formation
24
Q
  • What makes this agent specific?
A

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
25
Q
  • What is remdesivir a nucleoside analogue of?

- What class of drugs do both Amantidine and rimantadine both belong to?

A

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

Adamantanes

26
Q
  • What is amantidine?

- How does amantidine work?

A

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

27
Q
  • What is one of the disadvantages of using amantadine?
A

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
28
Q
  • Why is neuraminidase essential in the actions of influenza?
A

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
29
Q

what are the three neuraminidase inhibitors

  • Why was Relenza not such a successful drug as Tamiflu?
A

sialic acid, relenza, tamiflu

Because the chemistry of Relenza means the virus more readily acquires resistance
30
Q

What is Baloxavir

  • What is meant by Biologicals?
A

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)
31
Q
  • Give 5 of the ways in which HIV replication can be inhibited?
A

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
32
Q
  • What is an immunomodulator?
  • What is Dexamethasone?
  • What is Toculizimab?
A

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
33
Q

What is palivizumab

A

humanized monoclonal antibody against the pre fusion F protein of RSV

34
Q

what are the mechanisms of directly targeting antivirals against hepatitis C

A

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

35
Q

What properties do antivirals against influenza must have

A

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

36
Q

how has HIV been cured before

A

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

POM (47 decks)

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