Antiviral drugs Flashcards

1
Q

What are the features of the influenza genome?

A
  1. Eight segments
  2. ssRNA
  3. Negative sense
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2
Q

What is the function of the influenza M2 ion channel?

A

Triggers uncoating of genome when virus is exposed to low pH

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3
Q

What surrounds the influenza nucleocapsid?

A

Lipid bilayer envelope

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4
Q

Which two spike proteins are located in influenza envelope?

A
  1. Haemagglutinin

2. Neuraminidase

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5
Q

What is the function of haemagglutinin?

A

Mediates initial attachment of virus to host cell

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6
Q

How is the influenza nucleocapsid released from its envelope?

A

Haemagglutinin undergoes structural rearrangement following attachment, endocytosis and acidification

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7
Q

What is the function of neuraminidase?

A
  1. Prevents viral aggregation
  2. Facilitates release from host cells
  3. Possible role as virulence factor
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8
Q

What is responsible for antigenic drift and shift in influenza?

A

Variations and mutations in neuraminidase and haemagglutinin

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9
Q

What do anti-herpes agents target?

A

Virally-encoded DNA polymerases

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10
Q

How do viral DNA polymerases act?

A

In the same manner as eukaryotic DNA polymerases

Join 5’-OH of base being added to 3’-OH of sugar in polymerised strand of DNA

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11
Q

What is the distinguishing feature of purine analogues?

A

All lack cyclic sugar of 2’-deoxyguanosine

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12
Q

Why is aciclovir selective for virus-infected cells?

A
  1. Only virus-infected cells have thymidine kinase required to monophosphorylate drug
  2. Drug preferentially binds to viral DNA polymerase
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13
Q

Why do ganciclovir and penciclovir permit chain extension?

A

They have 3’OH moieties

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14
Q

What is contained in an HIV virion?

A
  1. Two copies of ssRNA genome
  2. Reverse transcriptase
  3. Aspartic protease
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15
Q

What is the role of HIV reverse transcriptase?

A

Converts ssRNA to dsDNA

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16
Q

How is HIV DNA integrated into the human genome?

A

Integrase enzyme

17
Q

What are the properties of the HIV reverse transcriptase?

A
  1. Poor fidelity
  2. Many frequent transcription errors
  3. High degree of sequence variation among viral genome copies that are produced
18
Q

What is the role of the HIV aspartic protease?

A

Cleaves polyprotein allowing maturation of HIV proteins and capsid formation

19
Q

How do non-nucleoside reverse transcriptase inhibitors work?

A

Bind to enzyme near catalytic site and denature it

20
Q

How do nucleoside reverse transcriptase inhibitors work?

A

Bind to target enzyme by mimicking naturally occurring nucleosides and terminate DNA chains once they are incorporated because they lack a 3’OH moiety

21
Q

How are nucleoside reverse transcriptase inhibitors activated?

A

Phosphorylated by host cell enzymes

22
Q

What is often co-administered with pyrimidine analogues?

A

Hydroxyurea

23
Q

What is the role of hydroxyurea?

A

Inhibit ribonucleotide reductase

24
Q

What is the effect of inhibiting ribonucleotide reductase?

A

Decreases intracellular pool of pyrimidine nucleotides

25
What is the mRNA transcribed from the HIV provirus translated to?
Gag proteins
26
What are gag proteins?
Biochemically inert polypeptides
27
How are gag polypeptides converted to functional proteins?
Cleaved by HIV protease at the appropriate positions as virus is budding from the cell membrane or shortly after
28
What does HIV protease have in its active site?
Two aspartyl residues
29
What are interferons?
Potent immunoregulatory cytokines synthesised in response to viral infection, causing biochemical changes that inhibit viral propagation
30
Which interferons have antiviral activity?
IFN-α and IFN-β
31
Which interferon has antitumour activity?
IFN-α
32
How do interferons work?
1. Bind to specific ganglioside receptors on host cell membranes 2. Promote production of enzymes that inhibit transcription of viral mRNA in host cell ribosomes
33
What is IFN-α-2a used to treat?
1. Hepatitis B infections | 2. AIDS related Kaposi's sarcoma
34
What is IFN-α-2b used to treat?
Hepatitis C