Module 5 - antiviral drugs

Question 1

What are the different classifications of pathogens and what is their individual risk level?

Answer 1

Class 1 - No risk or limited ris (E. coli)
Class 2 - limited access to lab, lab coat required, laminar hoods used (Herpes)
Class 3 - Risk of death or serious illness (HIV, Y. Pestis)
Class 4 - Lethal, highly infectious, untreatable

Question 2

Describe the general structure of a virus

Answer 2

Protein capsid surrounding genetic material. Some capsids also contain viral proteins
and enzymes. Enveloped viruses are surrounded by a membrane containing viral
proteins.

Question 3

Describe the stages of a typical viral life cycle.

Answer 3

1. Adsorption and penetration
2. Capsid opens releasing DNA or RNA
   3.Synthesis of regulatory proteins which alter the function of the cell
3. Synthesis of viral genetic molecules
4. Synthesis of structural proteins
5. Assembly of viral particles
   7.Release from cell – can be lytic (cell destroyed) or budding (cell survives)

Question 4

Which of the stages of the viral cycle is the most likely to be targetted?

Answer 4

4. Synthesis of viral genetic molecules
   —> Possible to target with drugs – most antivirals target this phase

Question 5

What are a few difficulties in developing antiviral drugs?

Answer 5

Each virus is unique, therefore each virus requires a different drug.

Most viral proteins act by binding to host proteins, making them very difficult to target with drugs due to the larger surface area of proteins, meaning that the drug must be a larger molecule to prevent the binding of either protein.

Question 6

How do you block viral enzyme without blocking the host enzyme?

Answer 6

you cant be as selective since both enzymes are involved in similar function, therefore similar structure

Question 7

What makes targetting viral proteins so hard?

Answer 7

Similarity to human proteins, as well as the small genomes = limited # of targets. Viruses have as few as 10 genes, on average 1 or 2 enzymes involved in nucleic acids (host selectivity problem)

Question 8

What are three problems with antiviral drugs?

Answer 8

Selectivity: Kill virus without killing host
Diagnosis: Drugs are specific for each virus, many viruses produce similar symptoms, only way to know for sure is through a biochemical test.
Resistance: Mutation rates in viruses is very high, viruses quickly develop resistance to drugs (days or weeks)

Question 9

Adsorption and penetration are poor drug targets

Answer 9

Binding involves protein-protein interactions which are difficult to inhibit.

Limited success in HIV

Question 10

Release of viral nucleic acid

Answer 10

Capsid opens releasing genetic info to the cell, difficult to target with drugs. (Protein interactions, pH changes)

Question 11

Synthesis of regulatory proteins

Answer 11

Viral proteins are made, “take over” normal cell systems, expression of viral protein

Question 12

Synthesis of RNA or DNA

Answer 12

-Viral genome is replicated using host enzymes
-Some viruses have their own enzymes for this (drug targets)
Most anti-virals target this phase
- Require unique viral enzyme

Question 13

What is the most targeted stage in drug synthesis?

Answer 13

DNA or RNA synthesis

Question 14

herpes structure

Answer 14

Genetic information is double stranded DNA:
70 genes –> very complex virus
Carries its own polymerase, drug target

Question 15

Idoxuridine

Answer 15

• Isn’t selective to herpes virus cuz it’s a substrate for viral and host polymerase
  topical use only

Question 16

Acyclovir

Answer 16

High selectivity for virally infected cells, selectivity is primarily due to selective bioavailability.

• PRODRUG, selective to prodrug, becomes active when its phosphorylated.