Anti-Virals

Question 1

What are the targets for anti-viral drugs?

Answer 1

Viral glycoprotein envelope uncoating, DNA/RNA polymer synthesis, viral release.

Question 2

What are the challenges in developing effective anti-viral agents?

Answer 2

Viruses are intercellular parasites so they are hard to target whilst avoiding host toxicity. It is also hard to design culture systems for viruses as they require host cells. Viruses are often host-specific so animal tests don’t yield much information.

Question 3

What drugs target viral glycoprotein envelope uncoating?

Answer 3

Amantadine, rimantadine.

Question 4

What was amantadine used for before it was used as an anti-viral drug?

Answer 4

An anti-parkinsonian medication.

Question 5

Chemically, what type of drugs are amantadine and rimantadine?

Answer 5

Tricyclic amines.

Question 6

What type of virus are amantadine and rimantadine only effective against?

Answer 6

Influenza A.

Question 7

Apart from its narrow spectrum of activity, what other problem might there be with using amantadine/rimantadine?

Answer 7

It may be difficult to build up high enough concentrations of the drug.

Question 8

What serious side effect can amantadine and rimantadine have? Which drug has a greater risk of causing this?

Answer 8

Neurotoxicity. Amantadine has a greater risk of causing neurotoxicity than rimantadine.

Question 9

What drugs prevent the release of viruses from the host cell?

Answer 9

Oseltamivir (tamiflu) and zanamivir (relenza).

Question 10

What have large-scale trials shown about the efficacy of oseltamivir and zanamivir?

Answer 10

That they may be no more effective than placebos.

Question 11

What are oseltamivir and zanamivir indicated for?

Answer 11

They are indicated for the treatment of influenza A and B within 24-48 hours of symptom onset. They are also indicated for prophylaxis of these infections.

Question 12

How do oseltamivir and zanamivir act to prevent the viral release from the host cell?

Answer 12

They block the action of the enzyme neuraminidase, which cleaves the terminal sialic acid residues attached to glycoproteins and glycolipids, a process necessary for the release of the virus from host cells.

Question 13

How is oseltamivir administered?

Answer 13

Orally.

Question 14

How is zanamivir administered?

Answer 14

Orally or by inhalation.

Question 15

How is oseltamivir excreted?

Answer 15

Renally.

Question 16

What are the side effects of zanamivir?

Answer 16

Reactive airway disease.

Question 17

What are the side effects of oseltamivir?

Answer 17

Nausea and vomiting.

Question 18

What drugs inhibit viral DNA/RNA synthesis?

Answer 18

Anti-herpesvirus drugs such as famciclovir, ganciclovir, idoxuridine, trifluridine.

Question 19

How do anti-herpesvirus agents work?

Answer 19

They are either analogues of pyrimidine or purine nucleotides, they competatively inhibit the enzymes used for DNA/RNA synthesis.

Question 20

Describe the structure of famciclovir and ganciclovir.

Answer 20

They are purines with incorrect sugar groups attached to them.

Question 21

Describe the structure of idoxuridine and trifluridine.

Answer 21

They are molecules in which the sugar part of the molecule is correct but the pyrimidine is incorrect.

Question 22

Why must one part of the nucleotide analogue anti-herpesvirus agents be the same as the molecule they resemble?

Answer 22

So they can be recognised by the enzyme which they are designed to inhibit the action of. If they were too different from the molecules they resemble, the enzyme wouldn’t recognise them and they wouldn’t be able to inhibit the enzyme.

Question 23

What is one of the most commonly used anti-viral drugs?

Answer 23

Acyclovir.

Question 24

Which anti-viral drug is an acyclic guanosine analogue?

Answer 24

Acyclovir.

Question 25

How does acyclovir work to prevent viral DNA/RNA replication?

Answer 25

It is preferentially taken up by virally infected cells, is it phosphorylated by viral kinases and then di- and tri-phosphorylated by cellular kinases. It then acts as a competitive inhibitor of viral DNA polymerase. This leads to viral DNA chain termination.

Question 26

What are the side effects associated with acyclovir use?

Answer 26

Headache, nausea, renal toxicity, neurotoxicity.

Question 27

What drug is used as an antiviral agent primarily in the eye?

Answer 27

Trifluridine.

Question 28

Where is the anti-herpesvirus drug trifluridine primarily used?

Answer 28

The eye.