Antimicrobial compounds and modes of action - Part 3 (antivirals)

Question 1

Why is selectivity with antivirals more challenging?

Answer 1

Because viruses use many host functions to replicate, so antivirals can have many side effects.

Question 2

What are 2 possible MOA for antivirals?

Answer 2

They must either block entry/exit from cell or be active inside the host cell

Antivirals are most active when virus is replicating

Question 3

Give 3 examples of antiviral classes/MOA

Answer 3

DNA polymerase inhibitors
Protease inhibitors
Reverse transcriptase inhibitors

Question 4

Give the mechanism of action for antivirals that inhibit DNA polymerase.

Give 2 examples of this

Answer 4

Interfere with DNA replication. DNA polymerase inhibitors are incorporated into DNA during normal replication. The lack of a 3’ hydroxyl group prevents the incorporation of the next nucleotide (i.e. chain termination)

Question 5

Describe the mechanism of action of reverse transcriptase inhibitor antivirals

Give 2 examples

Answer 5

Active against retroviruses

Nucleoside analogue reverse transcriptase inhibitors (NRTI)
Inhibit the reverse transcription of viral RNA genome (RNA - DNA)

e.g. tenofovir, azidothymidine

Question 6

How do antivirals that are protease inhibitors work?

Give 2 examples

Answer 6

They prevent the release of mature viral proteins from the polyproteins during viral life cycle.
No mature proteins = no virus packaging

E.g. nelfinovir, ritonavir

Question 7

What is highly active antiretroviral therapy (HAART)?

Answer 7

It is a combinational therapy
At least 3 drugs (NRTIs and protease inhibitors)
Powerful multifaceted attack employing different mechanisms of activity

Simultaneous blockade of multiple steps essential for viral activity and reproduction.