31. Anti-viral drugs

Question 1

What is a virus that has formed and is active outside the host cell called?

Answer 1

Virion - the complete, infective form of a virus

Question 2

Is Hepatitis B and C an RNA or DNA virus

Answer 2

• Hep B - DNA

* Hep C - RNA

Question 3

When is Hepatitis B and C treated?

Answer 3

Only when there is a chronic infection

this is associated with chronic liver inflammation which may result in cirrhosis and hepatocarcinoma

Question 4

What is the treatment for hepatitis B?

Answer 4

Tenofovir
• Nucleotide analogue
• Reverse transcriptase inhibitor

(Even though it is a DNA virus (which wouldn’t usually need reverse transcriptase) it has a complex replication cycle which needs it)

Question 5

What is the treatment for hepatitis C?

Answer 5

Ribavirin
• Nucleoside/purine analogue
• Prevents viral RNA synthesis

Boceprevir
• Protease inhibitor
• Most effective against genotype 1
• Prevents cleavage of a part of the virus, so it can’t be released from the cell (to become a virion)

Question 6

Outline the HIV life cycle

Answer 6

Attachment
• Viral membrane proteins interact with leukocyte membrane receptors
• HIV gp120 attaches to CD4 (CD40 co-stimulatory ligand involved)
• gp120 also binds to either CCR5 or CXCR4 co-receptors
• GP41 penetrates the membrane
• Viral capsid endocytosis

Replication and integration
• Within the cytoplasm, reverse transcriptase converts viral (ss) RNA => (ds) DNA
• DNA transported into the nucleus and integrated into the host DNA - using integrase
• This takes place over a couple of days, and can’t be cured after this point

Assembly and release
• Host cell used to produce viral RNA and essential proteins
• HIV protease cleaves the Gag precursor protein
• Gag precursor encodes all viral structural proteins
• Virus assembled within cell and mature virion is released

Question 7

Name 2 HIV entry inhibitors

Answer 7

Enfuvirtide and Maraviroc

Question 8

How does Enfuvirtide work?

Answer 8

Binds to HIV GP41 transmembrane glycoprotein, preventing fusion and entry

Question 9

How does Maraviroc work?

Answer 9

Blocks CCR5 chemokine receptor, so it can’t be found by gp120 and HIV can’t enter

Question 10

What is the delta 32 mutation?

Answer 10

5% of the population do not have CCR5 and do not get infected with HIV

Question 11

Is HIV an RNA or DNA virus?

Answer 11

RNA virus

Question 12

What are the types of drugs that can be used in HIV combination therapy (HAART)?

Answer 12

• Entry inhibitors
• Replication inhibitors (reverse transcriptase inhibitors)
• Integrase inhibitors
• Protease inhibitors

Question 13

Give an example of a nucleoside reverse transcriptase inhibitor

Answer 13

Zidovudine (AZT)

activated by a 3-step phosphorylation process

Question 14

Give an example of a nucleotide reverse transcriptase inhibitor and describe how it works

Answer 14

Tenofovir
• Binds to the active site of the reverse transcriptase enzyme
• Works for Hep B

(fewer phosphorylation steps required than AZT)

Question 15

Describe the most used antiretroviral drug used for HIV?

Answer 15

Efavirenz
• Non-nucleoside reverse transcriptase inhibitor
• Not incorporated into viral DNA
• Binds to allosteric sites on reverse transcriptase
• No phosphorylation required

Question 16

Give an example of an integrase inhibitor and explain why they are being used more commonly

Answer 16

Raltegravir
• More common due to increased resistance to usual combination therapy
• More tolerated and less likely to develop resistance

Question 17

What is saquinavir and ritonavir and what do they do

Answer 17

Both are protease inhibitors

Saquinavir - 1st generation
Ritonavir (low dose) - co-administered as a booster as it also reduces PI first pass metabolism (CYP450 inhibitor)
• Lots of drug-drug interactions

Question 18

What is the viral load of someone on HIV antiretroviral therapy?

Answer 18

Close to 0, so they can’t transmit it

Question 19

Is HSV an RNA or DNA virus?

Answer 19

(ds) DNA virus

Question 20

What surrounds HSV?

Answer 20

Surrounded by tegument and enclosed in a lipid bilayer

Question 21

Briefly describe the treatment for HSV?

Answer 21

Acyclovir
• Nucleoside (guanosine) analogue
• Only becomes active in infected cells (needs viral thymidine kinase and other kinases to be converted to active form)
• Acts as a chain terminator in DNA replication

Can be used to treat VZV and EBV

Question 22

Is influenza an RNA or DNA virus?

Answer 22

Multipartite ss RNA virus

Question 23

What is the envelope protein of influenza called and how does it interact with the host cell?

Answer 23

Neuraminidase, cleaves sialic acid on the host cell so that it can be released

Question 24

What does influenza usually infect in the body?

Answer 24

Nose, throat and bronchi

Question 25

What is the treatment for influenza?

Answer 25

Neuraminidase inhibitor - oseltamivir

must be inhaled as soon as you are infected, as it is too late to treat symptomatic patients

Question 26

What is a retrovirus?

Answer 26

RNA virus that uses reverse transcriptase to transcribe their RNA into DNA, which can be incorporated into cellular DNA