Mechanism of antivirals

Question 1

What do antibiotics treat? and What does anti-virals do?

Answer 1

Antibiotics –> Bacteria

Anti-virals –> Viruses

Both ‘antimicrobials’

Question 2

What are anti-viral drugs needed?

Answer 2

• as there isn’t a vaccine for some viruses, or poorly effective ones
• not every virus can be administered via a vaccine
• immune response from a vaccine can take time

For example:

• Acute infection - influenza
• HIV - post-exposure prophylaxis
• Acute inflammatory - herpes
• Chronic infection - Hep B and C

Question 3

What are the principles of anti-viral drugs as therapeutic agents?

Answer 3

• to inhibit virus replication without harming the infected cell
  
  • target protein in virus, not infected cell due to differences in structure and metabolic pathways between host and pathogen
• to induce selective toxicity

Question 4

Describe briefly the overview of the virus life cycle

Answer 4

Question 5

How can anti-virals take action?

Answer 5

• Preventing virus absorption
• Preventing penetration
• Preventing replication
• Preventing maturation of virus
• Preventing virus release

Question 6

Why is it so difficult to develop effective, non-toxic anti-viral drugs?

Answer 6

• Viruses use cellular proteins which may have other functions
• Viruses must replicate inside cells
• Viruses take over the host cell replicative machinery
• Viruses have high mutation rate
• Anti-virals must be selective in their toxicity
• Some viruses are able to remain in a latent state

Question 7

What is acyclovir?

Answer 7

targets herpes virus, Varicella zoster virus (chickenpox and shingles) and CMV

• only works in virus affected cells
• is converted from inactive to active inside the cell by viral enzyme by increasing the number of phosphate residues
• Very selective and effective and safe. Has a low background toxicity
• If there is mutations in the 2 main mechanisms: thymidine kinase mutants and DNA polymerase, the virus becomes resistant to acyclovir (very rare)

Question 8

What is HAART?

Answer 8

= treats HIV which is a combination of the anti-virals: anti-reverse transcriptase inhibitors (causes chain termination and no longer DNA replication, so no virus no disease) and protease inhibitors

• Treatments for post and Pre-exposure prophylaxis
• Selection pressure and mutation frequency leads to increased mutation rate and for a quasispecies within a individual –> viral swarm (many different HIV genomes present)

Question 9

What can treat influenza?

Answer 9

Amantadine used to treat influenza - inhibits virus uncoating by blocking the protein when inside cells

Zanamivir and Oseltamivir now have taken over to treat influenza and work by inhibiting virus release

Question 10

What do ribavirin/HCV inhibitors do?

Answer 10

Treat hep C virus

Transmitted by blood and very infection and increasingly common

Vaccination not available

Ribavirin is activated within the cell cause chain termination and so no RNA, no virus, no disease

• Very easy to get anti-viral resistance mutations which will drive the virus

HCV inhibitors are now more used and shorten the length of therapy, minimise side effects

Question 11

What happens so there is resistance to anti-virals?

Answer 11

Use of single agents leads to rapid development of resistance

The drug binding site is altered in structure by as few as one amino acid substitution

Mutation rate is high and viral load is high –> resistance

Question 12

What is post-exposure prohylaxis?

Answer 12

• Treating post-infection, post-exposure to a potential infected product
• If done fast enough and vigorously, it is very effective
• For example HIV, Hep B and C

Question 13

What types of viruses are not treatment and have no effective therapies?

Answer 13

• Rabies
• Dengue
• Ebola
• Common cold virsues