Anti-virals Flashcards
What surrounds the genetic material in viruses? What may surround this?
Capsid (protein shell)
Surrounded by a lipid envelope which contains envelope proteins.
What type of genetic material do the following viruses have:
a. Hepatitis B
b. Hepatits C
c. HIV
d. Herpes Simplex Virus
e. Influenza
a. Hepatitis B Hepadnavirus – it is a DNA virus that also involves reverse transcriptase in its replication b. Hepatitis C RNA virus c. HIV Retrovirus d. Herpes Simplex Virus DNA virus e. Influenza RNA virus
Describe the relative curability of Hep B and Hep C.
Hep B – not curable
Hep C – CURABLE
At what point do you start treating someone who has recently got infected by Hep B or Hep C?
When the infection becomes chronic
The immune system, in some people, is able to clear Hep B and Hep C infections by itself
What is the treatment for Hep B? What type of drug is this? What is it sometimes given with?
Tenofovir
= Nucleotide analogue which inhibits the activity of reverse transcriptase
- given sometimes with Peginterferon alfa
What are the treatment options for Hep C? State the drug types.
- Ribavirin & Peginterferon alfa
= Ribavirin is a nucleoside analogue (purine analogue) which prevents RNA synthesis - Boceprivir = protease inhibitor (only works on Hep C genotype 1)
In the treatment of HCV today, the specific drugs and the duration of treatment depend on what factors?
- HCV genotype (genetic structure of the virus)
- viral load
- past treatment experience
- degree of liver damage
- ability to tolerate the prescribed treatment
- need for liver transplant
HIV life cycle;
Attachment & Entry
- Viral membrane proteins interact with leukocyte membrane receptors
- Viral capsid endocytosis
HIV life cycle;
Replication & Integration
Within cytoplasm - reverse transciptase enzyme converts viral RNA => DNA
DNA transported into nucleus & integrated into host DNA
HIV life cycle;
Assembly & Release
Host cell’s ‘machinery’ utilised to produce viral RNA & essential proteins
Virus is assembled within cell => mature virion is released
Describe the receptor interaction involved in HIV attachment and entry.
- HIV Glycoprotein (GP)120 attaches to CD4 receptor
- GP120 also binds to either CCR5 or CXCR4
- GP41 penetrates host cell membrane & viral capsid enters
State two drugs that interfere with HIV attachment and entry and state their targets.
Enfuvirtide
= Binds to HIV GP41 transmembrane glycoprotein
Maraviroc
= Blocks CCR5 chemokine receptor
What are the three drug classes which interfere with HIV replication?
Nucleoside RT inhibitors
Nucleotide RT inhibitors
Non-nucleoside RT inhibitors
Name a nucleoside reverse transcriptase inhibitor. How are they activated?
Zidovudine
Three step phosphorylation
Name a nucleotide reverse transcriptase inhibitor. Activation?
Tenofovir
Fewer phosphorylation steps required
How do non-nucleoside reverse transcriptase inhibitors act? Give an example of an NNRTI.
Activation?
They bind to the reverse transcriptase and cause a change in shape of the enzyme so it blocks HIV replication (so it is not incorporated into the viral DNA)
Example: Efavirenz
No phosphorylation required for activation
What enzyme inserts viral DNA into host DNA?
viral integrase
Give an example of an integrase inhibitor.
Raltegravir
What viral gene encodes all the viral structural proteins?
Gag gene
What must happen to the protein product of this gene, in order to produce fully functioning virus particles?
This must be cleaved by a protease into the constituent proteins so that it can make the fully formed virus
Name a drug that acts a protease inhibitor and state one problem with its pharmacokinetics.
Saquinavir
It has a low bioavailability
What drug can be given to boost the level of the protease inhibitor in the circulation?
Ritonavir
This decreases the metabolism of saquinavir
Describe the structure of the herpes simplex virus
Double-stranded DNA
Surrounded by tegument & enclosed in a lipid bilayer
What do the two different types of herpes cause?
HSV1 – cold sores
HSV2 – genital herpes
What is the treatment for HSV?
Acyclovir
Nucleoside analogue that is specific because its activation requires viral kinases
Describe the genetic material inside the influenza virus.
What envelope protein of influenza is important for the release of the virus into the host cell?
Multipartite single stranded RNA virus
Envelope protein important for the release = neuraminidase
Name a Neuraminidase inhibitor
Oseltamivir
