Principles of Anti-Viral Chemotherapy Flashcards
What are anti-viral agents mainly used for?
To control those viral infections with high morbidity and mortality
What is the problem with anto-viral chemotherapy?
They are still developing, and some serious viruses still have no specific therapy
What does the life cycle of a virus provide?
Numerous target steps for anti-viral drugs to act on to prevent the infection and spread of the virus
What steps of the viral life cycle can be used as targets?
- Adsorption onto the surface of the host cell via attachment
- Penetration into the cell via fusion with the plasma membrane and then entry via the endosome
- Uncoating of the viral DNA so that it can be made available for interaction with the host cell DNA
- Viral proteins synthesis by host cell
- New viruses are released from cell via lysis or budding
Draw a diagram illustrating the viral life cycle
What are the main classes of anti-viral drugs?
- Nucleoside analouges
- Amantadine
- Highly active anti-retroviral therapy (HAART)
How do nucleoside analogues work?
They are taken up into the cell and converted to a form of nucleoside that will prevent any further synthesis of viral proteins in the cell by inhibiting RNA polymerase
Give two examples of nucleoside analogues
- Aciclovir
- Ganciclovir
What is aciclovir used against?
HSV and VZV
What is the mechanism of action of aciclovir?
It is converted to a monophosphate form upon entering the cell by the viral enzyme thymidine kinase. This is then converted to triphosphate form by the host which inhibits the action of RNA polymerase
What is the advantage of aciclovirs mechanism of action?
It is only potent against virally infected cells
What is the mechanism of action of ganciclovir?
It is coverted to a triphosphate form and the resulting guanosine triphosphate inhibits any further protein synthesis
What is ganciclovir used for?
CMV infections, especially in immunocomprimised individuals
How does amantadine work?
Prevents the uncoating and release of viral DNA
What is the problem with amantadine?
Viral resistance is developing quickly
What is the result in the rapid growth of viral resistance to amantadine?
Only short courses are used to prevent disease
What is HAART used against?
HIV infections
What has HAART been shown to do?
Decrease the viral load and maintain CD4+ levels for a significant period of tiem
Give 3 examples of HAARTs
- Nucleoside reverse transcriptase inhibitors (NRTIs)
- Non-nucleotide reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors
What are NRTIs?
Nucleoside analogues that are converted to 5’-triphosphate derivatives in the cell
How do NRTIs work?
Once incorporated into the viral DNA chain, they inhibit any further growth
What is the main example of NRTIs?
Zibovudine
What is zibovudine an analouge of?
Thymidine
What do NNRTIs do?
Inhibit NRTIs
What are the main examples of NNRTIs?
- Nevirapine
- Delaviridine
What are the most effective anti-retroviral compounds?
Protease inhibitors
How do protease inhibitors work?
By inhibiting the action of protease enzymes which are only found in virally infected cells, which will normally convert polyproteins (from mRNA) of the virally infected cells into viral proteins
Give two examples of protease inhibitors
- Atazanivir
- Indinavir
When does HAART work best?
When all the therapies are used concurrently
What are the main limitations of antiviral therapy?
- The narrow spectrum of activity
- The low therapeutic values (before side effects set in)
- Drug resistance may occur
