What are the problems associated with anti-viral therapy?
Virus hijacks host- hard for the immune system to detect friend from foe.
Overwhelming proliferation of virus particles
Viruses have a rapid mutation rate.
Viruses impair the host's immune response
Viruses can integrate their genetic material into host chromosome= clinical infection can arise without re-exposure.
What are the 4 main types of anti-viral therapy?
Reverse transcriptase inhibitors
Absorption and fusion inhibitors
Anti-viral cytokine therapy
What is the anti-drug treatment aimed at?
HIV/AIDS- mostly infects T4-lymphocytes of the immune system, cells that express the CD4 receptor.
Explain the life-cycle of the HIV virus?
1. Binding of virus to cell surface.
2. Entry of virus in to cytoplasm.
3. Uncoating of viral RNA.
4. Viral reverse transcriptase produces viral DNA.
5. Integrated into host chromosome.
6. Use of host mechanisms to multiply and produce viral mRNA.
7.Translation of viral proteins from mRNA.
8.Processing of viral proteins(trimming, glycosylation)
9. Assembly of progeny virions at cell membrane.
10. Release of progeny by budding.
What are the three targets for anti-viral drugs in the life cycle of HIV virus?
1.Reverse transcriptase inhibitors- conversion of viral RNA to DNA eg NRTIs, nNRTIs
2. Protease inhibitors- protein assembly and packaging
3. Fusion inhibitors- Viral-cell fusion
Why are a combination of therapeutic approaches used and what is the combination therapy called?
A combination of drugs is used so that the virus soesn't develop resistance.
Current therapy- HAART- highly active anti retroviral therapy(mix of RTIs and PIs)
Give an example of a nucleoside reverse transcriptase inhibitor?
-effective antiretroviral but subject to rapid resistance.
-selective for viral RT and does not affect mammalian DNA polymerase
-associated with haematological toxicity, pancreatis, liver damage and severe anaemia.
Mechanism of action- Zidovudine(prodrug) enters the cell and is triple phosphorylated by various cellular nucleoside kinases before it can react with viral reverse transcriptase to halt DNA synthesis.
Give an example of non-nucleoside reverse transcriptase inhibitors?
It has serious adverse effects including life-threatening skin reactions and liver damage.
What is the mechanism of action of protease inhibitors?
-Block the processing of viral protein and assembly of the virion.
-Bind to the active site of the protease , leaving proteins uncleaved and inactive
Side effects- nausea, vomiting and diarrhoea
Give an example of first fusion inhibitor and its function?
-Inhibits the entry of HIV into host CD4 lymphocytes.
Side effects- flu like symptoms, GI effects, alterations in mood, headaches and dizziness, hypersensitivity reactions.
Give an example of cytokine therapy and what is it used to treat?
Interferon(INF-a)- treatment of hepatitis C
-INF-a is secreted by cells in response to viral infections.
- Augments the host immune system and target cell killing by lymphocytes and inhibits viral replication
What are the side-effects of interferon-a?