Antivirals

Question 1

What are examples of anti-influenza drugs?

Answer 1

1. Amantidine
2. Osltamivir and zanamivir

Question 2

What is the mechanism of action of amantidine?

Answer 2

• Early infection: Binds to and blocks M2 channels needed for initiation of fusion process
• Late infection: Interferes with synthesis and processing of haemagglutinin

Question 3

What is the mechanism of action of oseltamivir and zanamivir?

Answer 3

• Structural analogues of sialic acid (N-acetylneuraminic acid)
• Inhibits neuraminidase competitively

Question 4

What are examples of antiherpes drugs?

Answer 4

1. Aciclovir
2. Ganciclovir (CMV selective)
3. Cidofovir (CMV selective)
4. Foscarnet

Question 5

What is the mechanism of action of aciclovir?

Answer 5

Purine (guanosine analogue)

1. Within the infected cell, it is phosphorylated to MP form by viral thymidine kinase (only expressed in infected cells)
2. It is then converted to TP form by cellular kinases
3. Aciclovir-TP is 30x more selective for viral DNAP than mammalian DNAP and is incorporated into viral DNA
4. It is missing 3’ –OH group so acts as a chain terminator for viral DNA synthesis

Question 6

What is the mechanism of action of ganciclovir?

Answer 6

Purine (guanosine) analogue

1. It is converted to ganciclovir-MP by CMV-coded kinase
2. It is the converted to ganciclovir-TP by cellular kinases
3. Ganciclovir-TP has greater selectivity for viral DNAP
4. It also has 3’ –OH so permits chain elongation, albeit at a much decreased efficiency

Question 7

What is the mechanism of action of cidofovir?

Answer 7

Pyrimidine (cytosine) analogue

• Inhibits CMV DNAP

Question 8

What is the mechanism of action of foscarnet?

Answer 8

• Analogue of pyrophosphate
• Selectively inhibits the pyrophosphate binding site on viral DNAP
• Inhibits cleavage of PPi groups on nucleoside-TPs as they are added to growing polynucleotide chain in DNA synthesis

Question 9

What are the classes of drugs that can be used to treat HIV infections?

Answer 9

1. Nucleoside reverse transcriptase inhibitors
2. Non-nucleoside reverse transcriptase inhibitors
   - HIV protease inhibitors

Question 10

What is the mechanism of action of AZT (nucleoside reverse transcriptase inhibitor)?

Answer 10

Thymidine analogues

• Activated by host cell kinases
• Selective for RT and is incorporated in place of thymidine
• Azide group (-N₃) in place of 3’ –OH prevents chain elongation, allowing it to act as chain terminator

Question 11

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?

Answer 11

• Binds to allosteric site away form RT active site
• Probably inhibits conformational changes needed for RT action

Question 12

What are examples of non-nucleoside reverse transcriptase inhibitors?

Answer 12

1. Nevirapine
2. Efavirenz

Question 13

What is the mechanism of action of HIV protease inhibitors?

Answer 13

Intermediate analogue of HIV protease

• Binds to and reacts with HIV protease (Asp protease) active site but reaction cannot be completed (acid resistant –OH prevents acidic attack)
• Permanently occupies HIV protease active site and acts as suicide inhibitor

Question 14

What are examples of HIV protease inhibitors?

Answer 14

1. Saquinavir
2. Ritonavir
3. Lopinavir

Question 15

What are available interferon drugs and what are they used for?

Answer 15

1. INF-α-2a: Treat HBV and AIDS-related Kaposi sarcoma

INF-α-2b: Treat HCV

Question 16

What are other examples of immunomodulating drugs used to treat viral infections?

Answer 16

1. Hyperimmune globulins: Used to treat HBV, VZV and rabies infections
2. Palivisumab: Monoclonal antibody specific for surface glycoprotein on respiratory syncytial virus