Principles of Anti-Viral Chemotherapy

Question 1

What are anti-viral agents mainly used for?

Answer 1

To control those viral infections with high morbidity and mortality

Question 2

What is the problem with anto-viral chemotherapy?

Answer 2

They are still developing, and some serious viruses still have no specific therapy

Question 3

What does the life cycle of a virus provide?

Answer 3

Numerous target steps for anti-viral drugs to act on to prevent the infection and spread of the virus

Question 4

What steps of the viral life cycle can be used as targets?

Answer 4

• 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

Question 5

Draw a diagram illustrating the viral life cycle

Answer 5

Question 6

What are the main classes of anti-viral drugs?

Answer 6

• Nucleoside analouges
• Amantadine
• Highly active anti-retroviral therapy (HAART)

Question 7

How do nucleoside analogues work?

Answer 7

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

Question 8

Give two examples of nucleoside analogues

Answer 8

• Aciclovir
• Ganciclovir

Question 9

What is aciclovir used against?

Answer 9

HSV and VZV

Question 10

What is the mechanism of action of aciclovir?

Answer 10

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

Question 11

What is the advantage of aciclovirs mechanism of action?

Answer 11

It is only potent against virally infected cells

Question 12

What is the mechanism of action of ganciclovir?

Answer 12

It is coverted to a triphosphate form and the resulting guanosine triphosphate inhibits any further protein synthesis

Question 13

What is ganciclovir used for?

Answer 13

CMV infections, especially in immunocomprimised individuals

Question 14

How does amantadine work?

Answer 14

Prevents the uncoating and release of viral DNA

Question 15

What is the problem with amantadine?

Answer 15

Viral resistance is developing quickly

Question 16

What is the result in the rapid growth of viral resistance to amantadine?

Answer 16

Only short courses are used to prevent disease

Question 17

What is HAART used against?

Answer 17

HIV infections

Question 18

What has HAART been shown to do?

Answer 18

Decrease the viral load and maintain CD4⁺ levels for a significant period of tiem

Question 19

Give 3 examples of HAARTs

Answer 19

• Nucleoside reverse transcriptase inhibitors (NRTIs)
• Non-nucleotide reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors

Question 20

What are NRTIs?

Answer 20

Nucleoside analogues that are converted to 5’-triphosphate derivatives in the cell

Question 21

How do NRTIs work?

Answer 21

Once incorporated into the viral DNA chain, they inhibit any further growth

Question 22

What is the main example of NRTIs?

Answer 22

Zibovudine

Question 23

What is zibovudine an analouge of?

Answer 23

Thymidine

Question 24

What do NNRTIs do?

Answer 24

Inhibit NRTIs

Question 25

What are the main examples of NNRTIs?

Answer 25

• Nevirapine
• Delaviridine

Question 26

What are the most effective anti-retroviral compounds?

Answer 26

Protease inhibitors

Question 27

How do protease inhibitors work?

Answer 27

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

Question 28

Give two examples of protease inhibitors

Answer 28

• Atazanivir
• Indinavir

Question 29

When does HAART work best?

Answer 29

When all the therapies are used concurrently

Question 30

What are the main limitations of antiviral therapy?

Answer 30

• The narrow spectrum of activity
• The low therapeutic values (before side effects set in)
• Drug resistance may occur