Antivirals COPY

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 HIV infections AND WHICH PARTS OF the HIV INFECTION PROCESSS ARE AFFECTED

Answer 2

ATTACHMENT AND ENTRY(1. Entry inhibitors e.g. enfuviratide, maraviroc)REPLICATION( 2. Nucleoside/nucleotide reverse transcriptase inhibitors e.g. zidovudine 3. Non-nucleoside RT inhibitors e.g. efavirenz)

INTEGRATION(4. Integrase inhibitors e.g. raltegravir) ASSEMBLY AND RELEASE( 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) w/ low dose Ritonavir reduces PI metabolism , so it isco-administered as ‘booster’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: - . Then nucleotide RTi (tenofovir) w/Pegylated interferon (peginterferon) alpha SOMETIMES.

Chronic HCV: - Peginterferon + nucleotide analogue (ribavirin) - Protease(enzyme that helps in release of the virus from host) inhibitor (boceprevir)

Question 5

Which antivirals are used to treat herpes?

Answer 5

Nucleoside RT inhibitor Acyclovir(nucleoside analogue)

Question 6

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

Answer 6

Influenza neuraminidase inhibitor e.g. Oseltamivir inhibits neuraminidase –> virus can’t be released from the host cell and is destroyed there.

Question 7

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

Answer 7

HIV: retrovirus, leukocytes Hepatitis: DNA (hep b-still uses reverse transcriptase for some steps - not fully understood)and RNA viruses(hepC), hepatocytes Herpes Simplex: dsDNA virus (•Surrounded by tegument & enclosed in a lipid bilayer) Influenza: ssRNA virus

Question 8

Genral viral structure

Answer 8