Pharmacology: Antivirals

Question 1

How to antivirals differ from antibiotics? Can they be given empirically?

Answer 1

• antivirals act intracellularly whereas antibiotics act EC
• antivirals inhibit the virus and it is the role of the hosts immune system to kill it whereas antibiotics kill bacteria
• antivirals arent used empirically because they are very specific rather than broad spectrum

Question 2

What is the role of virus load testing in antiviral therapy? Give examples where this is used

Answer 2

• to see if the virus is resistant
• to monitor compliance
• to monitor efficacy of treatment

Viral load is monitored in HIV and Hep B

Question 3

What is the genetic barrier to resistance?

What is an ‘unfit’ virus?

Answer 3

The genetic barrier to resistance is how many mutations the virus needs to become resistant. Low GB = easily resistant
An unfit virus is a virus that mutates often and therefore can mutate so much it changes structure and decreases virulence.

Question 4

Outline the stages in viral replication and therefore the potential targets for antivirals

Answer 4

1. Virus has to attach to the cell eg HIV attaches to CD4 cell (get entry inhibitors)
2. Virus has to uncoat to open up so RNA can come out (can block this so that virus can enter but not replicate)
3. The virus then replicates its RNA/DNA (block and the virus cant replicate)
4. Protein synthesis from mRNA
5. There is assembly of the new virus via the host cell machinery
6. There is release/budding of the virus so it can spread to other cells (tamiflu acts here)

Question 5

What specific step does aciclovir act on its target virus?

What is the mechanism of drug resistance?

Answer 5

Acts on epstein-barr virus (activated by viral thymidine kinase) by inhibiting viral DNA polymerase which terminated DNA replication.
Resistance arises via absent TK enzyme, altered substrate or altered DNA polymerase.

Question 6

What specific step does Ribavirin act on its target virus?

What is the mechanism of drug resistance?

Answer 6

Ribavirin acts on Hep C by inhibiting RNA and DNA viruses - alters cellular nucleotide stores and alters mRNA synthesis.
Resistance is rare

Question 7

What specific step does Amantadine act on its target virus?

What is the mechanism of drug resistance?

Answer 7

Amantadine is an anti-influenza drug.
Works by inhibiting ion channel function on the virus, preventing normal pH-mediated uncoating.
Resistance arises readily with single AA substitutions.