Anti-viral drugs

Question 1

Describe the structure of a virus?

Answer 1

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

Question 2

Describe viral hepatitis B and C and the drugs used

Answer 2

Target the liver hepatocytes
- Chronic infection requires treatment

Hep B treatment: Not curable

• Tenofovir –> nucleotide analogue, given sometimes with Peginterferon alfa.
• It prevents the progression of the DNA synthesis
• Reverse transcriptase inhibitor

Hep C treatment: Curable (within 3 months)

• Ribavirin and Peginterferon alfa
• Ribavirin –> nucleoside analogue prevents viral RNA synthesis.
• Boceprevir –> protease inhibitor. Most effective against Hep C genotype 1. All three are taken in combination

Hepatits is an RNA and DNA virus

Question 3

Summarise the HIV life cycle

Answer 3

1) Attachment and Entry
- Viral membrane proteins interact with leukocyte membrane receptors
- Viral capsid endocytosis

2) Replication and Integration
- Within cytoplasm - reverse transciptase enzyme converts viral RNA –> DNA
- DNA transported into nucleus and integrated into host DNA

3) Assembly and Release
- Host cell’s ‘machinery’ utilised to produce viral RNA and essential proteins
- Virus is assembled within cell –> mature virion is released

HIV is a retrovirus (RNA)

Question 4

Describe HIV entry inhibitors

Answer 4

Attachment and Entry

• HIV Glycoprotein (GP)120 attaches to CD4 receptor
• GP120 also binds to either CCR5 or CXCR4
• GP41 penetrates host cell membrane and viral capsid enters

Enfuvirtide
- Binds to HIV GP41 transmembrane glycoprotein
Maraviroc
- Blocks CCR5 chemokine receptor

Question 5

Describe HIV replication inhibitors

Answer 5

Reverse transcription
Viral single-stranded RNA –> double stranded DNA by reverse transcriptase

1) Nucleoside RT inhibitors
Zidovudine
- Activated by 3 step phosphorylation process
- blocks the reverse transcription

2) Nucleotide RT inhibitors
Tenofovir
- Fewer phosphorylation steps required
- same mechanism as zidovudine

3) Non-nucleoside RT inhibitors
- No phosphorylation required
- Not incorporated into viral DNA
E.g. Efavirenz

Question 6

Describe HIV integrase inhibitors

Answer 6

DNA integration
Viral integrase inserts viral DNA into host DNA

1) Integrase inhibitors
Raltegravir - first of 3 licensed integrase inhibitors, target HIV integrases

Question 7

Describe HIV protease inhibitors

Answer 7

Assembly and Release

• Gag precursor –> encodes all viral structural proteins
• HIV protease cleaves Gag precursor protein

Protease inhibitors (PI)

• Saquinavir - 1st generation PI
• Low dose Ritonavir reduces PI metabolism –> co-administered as ‘booster’

Question 8

What is the treatment of herpes simplex virus?

Answer 8

HSV is treated by nucleoside analogues –> aciclovir
Prevents DNA replication - inhibits DNA polymerase

HSV-1 –> cold sores
HSV-2 –> genital sores
This is a DNA virus

Question 9

What is the treatment of influenza?

Answer 9

Neuraminidase inhibitor –> Oseltamivir (essentially prevents the release of the virus in the cell)

Envelope protein neuraminidase –> causes the release of the virus from the infected cell
This is a RNA virus