31. Anti-viral drugs Flashcards
(26 cards)
What is a virus that has formed and is active outside the host cell called?
Virion - the complete, infective form of a virus
Is Hepatitis B and C an RNA or DNA virus
- Hep B - DNA
* Hep C - RNA
When is Hepatitis B and C treated?
Only when there is a chronic infection
this is associated with chronic liver inflammation which may result in cirrhosis and hepatocarcinoma
What is the treatment for hepatitis B?
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)
What is the treatment for hepatitis C?
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)
Outline the HIV life cycle
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
Name 2 HIV entry inhibitors
Enfuvirtide and Maraviroc
How does Enfuvirtide work?
Binds to HIV GP41 transmembrane glycoprotein, preventing fusion and entry
How does Maraviroc work?
Blocks CCR5 chemokine receptor, so it can’t be found by gp120 and HIV can’t enter
What is the delta 32 mutation?
5% of the population do not have CCR5 and do not get infected with HIV
Is HIV an RNA or DNA virus?
RNA virus
What are the types of drugs that can be used in HIV combination therapy (HAART)?
- Entry inhibitors
- Replication inhibitors (reverse transcriptase inhibitors)
- Integrase inhibitors
- Protease inhibitors
Give an example of a nucleoside reverse transcriptase inhibitor
Zidovudine (AZT)
activated by a 3-step phosphorylation process
Give an example of a nucleotide reverse transcriptase inhibitor and describe how it works
Tenofovir
• Binds to the active site of the reverse transcriptase enzyme
• Works for Hep B
(fewer phosphorylation steps required than AZT)
Describe the most used antiretroviral drug used for HIV?
Efavirenz
• Non-nucleoside reverse transcriptase inhibitor
• Not incorporated into viral DNA
• Binds to allosteric sites on reverse transcriptase
• No phosphorylation required
Give an example of an integrase inhibitor and explain why they are being used more commonly
Raltegravir
• More common due to increased resistance to usual combination therapy
• More tolerated and less likely to develop resistance
What is saquinavir and ritonavir and what do they do
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
What is the viral load of someone on HIV antiretroviral therapy?
Close to 0, so they can’t transmit it
Is HSV an RNA or DNA virus?
(ds) DNA virus
What surrounds HSV?
Surrounded by tegument and enclosed in a lipid bilayer
Briefly describe the treatment for HSV?
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
Is influenza an RNA or DNA virus?
Multipartite ss RNA virus
What is the envelope protein of influenza called and how does it interact with the host cell?
Neuraminidase, cleaves sialic acid on the host cell so that it can be released
What does influenza usually infect in the body?
Nose, throat and bronchi
