Pharmacology 32 - Antiviral Drugs

Question 1

Describe viral structure

Answer 1

• Envelope proteins
• Lipid envelope
• Genetic material (RNA or DNA)
• Capsid (protein shell surrounding the genetic material of the virus)

Question 2

Describe tropism of viral hepatitis

Answer 2

Liver hepatocytes

Question 3

When is hep B and C treated?

Answer 3

Only in chronic infection

Question 4

Give an example of drugs used in Hep B treatment

Answer 4

DNA virus

• Tenofir (nucleotide analogue, blocks replication of viral DNA)
• Sometimes given with peginterferon alpha (activates viral immune response)

Question 5

Describe treatment of Hep C

Answer 5

RNA virus

• Ribavirin and peginterferon alfa
• Ribavirin is a nucleoside analogue prevents viral RNA synthesis
• Boceprevir is a protease inhibitor
• Most effective against Hep C genotype 1
• Goal is to cure the virus (use of combination of drugs)

Question 6

What does hepatitis C treatment depend upon?

Answer 6

• HCV genotype (genetic structure of the virus)
• Viral load
• Past treatment experience
• Degree of liver damage
• Ability to tolerate the prescribed treatment
• Need for liver transplant

Question 7

Describe the HIV life cycle

Answer 7

Attachment and Entry

• Viral membrane proteins interact with leukocyte membrane receptors (HIV glycoprotein GP120 attaches to CD4 receptor, and also either CCR5 or CXR4)
• Viral capsid endocytosis following GP41 penetrating host cell

Replication and Integration

• Within cytoplasm - reverse transciptase enzyme converts viral RNA to DNA
• DNA transported into nucleus and integrated into host DNA

Assembly and Release

• Host cell’s ‘machinery’ utilised to produce viral RNA and essential proteins
• All viral structural proteins encoded by gag precursor.
• Virus is assembled within cell, mature virion is released

Question 8

List HIV entry inhibitors

Answer 8

Enfuvirtide
- Binds to HIV GP41 transmembrane glycoprotein

Maraviroc

• Blocks CCR5 chemokine receptor
• Some people can have genetic mutation with no CCR5 receptor (naturally protected against HIV)

Question 9

List HIV replication inhibitors

Answer 9

Nucleoside reverse transcriptor (RT) inhibitors

• Activated by 3 step phosphorylation process
• E.g. Zidovudine

Nucleotide RT inhibitors

• Fewer phosphorylation steps required
• E.g. Tenofovir

Non-nucleoside RT inhibitors

• No phosphorylation required
• Not incorporated into viral DNA
• E.g. Efavirenz

Question 10

Describe HIV integrase inhibitors

Answer 10

• Normal viral integrase inserts viral DNA into host DNA

- Raltegravir - first of 3 licensed integrase inhibitors

Question 11

List HIV protease inhibitors

Answer 11

• HIV protease cleaves Gag precursor protein
• Saquinavir - 1st generation protease inhibitor (PI)
• Low dose Ritonavir reduces PI metabolism, co-administered as ‘booster’
• Both administered together

Question 12

Describe virology of herpes simplex

Answer 12

• dsDNA
• Surrounded by tegument (a cluster of proteins that lines the space between the envelope and nucleocapsid) and enclosed in a lipid bilayer

Question 13

Describe trophism of herpes simplex

Answer 13

• HSV1 cold sores

- HSV2 genital herpes

Question 14

How is herpes simplex virus treated?

Answer 14

• Nucleoside analogues (aciclovir)
• Block replication of viral DNA
• May be taken every day when there are multiple outbreaks, or taken for a short period of time when outbreak occurs

Question 15

Describe virology of influenza

Answer 15

• Multipartite single stranded RNA virus

- Envelope protein neuraminidase causes release

Question 16

What is trophism of influenza?

Answer 16

Nose, throat and bronchi

Question 17

How is influenza treated?

Answer 17

• Neuraminidase inhibitor

- Eg. Oeltamavir (tamiflu)

Question 18

Why is HIV a reterovirus?

Answer 18

• From RNA to DNA

- Normally from DNA to RNA