Antivirals

Question 1

How does HIV use the host cell to replicate?

Answer 1

1. Attachment and entry - viral membrane proteins (HIV glycoprotein 120) interact w/leukocyte membrane receptors (CD4/CCR5/CXCR4, GP41 penetrates host cell membrane); viral capsid endocytosis
2. Replication + integration - in cytoplasm, RT converts viral RNA to DNA; DNA transported into nucleus + integrated into host DNA by viral integrase
3. Assembly + release - host cell’s machinery used to produce viral RNA + essential proteins; Gag precursor encodes all viral structural proteins; HIV protease cleaves Gag precursor protein; virus assembled within cell; mature virion released

Question 2

What classes of drugs are used to treat viral infections?

Answer 2

1. Entry inhibitors e.g. enfuviratide, maraviroc
2. Nucleoside/nucleotide reverse transcriptase inhibitors e.g. zidovudine
3. Non-nucleoside RT inhibitors e.g. efavirenz
4. Integrase inhibitors e.g. raltegravir
5. Protease inhibitors e.g. saquinavir

Question 3

Which antivirals are used to treat HIV? How do they work?

Answer 3

1. Nucleoside reverse transcriptase inhibitors - target HIV RT (zidovudine) + nucleotide RT inhibitors
2. Protease inhibitors - prevent HIV proteases from cleaving emerging proteins required for development of a mature virion (saquinavir)
3. Non-nucleotide RT inhibitors (nnRTIs) - inhibit RT activity by allosteric inhibition (efavirenz)
4. Viral entry inhibitors - enfuvirtide prevents fusion of HIV w/host membrane by binding to glycoprotein GP41; maraviroc blocks CCR5 chemokine receptor which HIV uses to enter macrophages
5. Integrase inhibitors - target HIV integrase protein, which allows HIV DNA to be incorporated into host DNA (raltegravir)

Question 4

Which antivirals are used to treat hepatitis?

Answer 4

Chronic HBV:

• Pegylated interferon (peginterferon) alpha 2a
• Then nucleotide RTi (tenofovir)

Chronic HCV:

• Peginterferon + nucleoside RTi (ribavirin)
• Protease inhibitor (boceprevir)

Question 5

Which antivirals are used to treat herpes?

Answer 5

Nucleoside RT inhibitor

Acyclovir

Question 6

Which antivirals are used to treat influenza? How do they work?

Answer 6

• VACCINE better
• Post-exposure prophylaxis = neuraminidase inhibitors
• Prevents influenza reproduction by inhibiting budding from host cell

Question 7

Which antivirals are used to treat influenza? How do they work?

Answer 7

Influenza neuraminidase inhibitor

e.g. Oseltamivir inhibits neuraminidase –> virus can’t be released not the host cell

Question 8

Distinguish between different types of virus and describe how they use the host cell to replicate

Answer 8

HIV: retrovirus, leukocytes
Hepatitis: DNA and RNA viruses, hepatocytes
Herpes Simplex: DNA virus
Influenza: RNA virus