Tutorial 1 - Acyclovir

Question 1

What virus does acyclovir treat?

Answer 1

Herpes

Question 2

What nucleotide is acyclovir similar to?

Answer 2

Deoxyguanosine but it does not have the 3’ Hydroxyl group

This means that acyclovir cannot attach to other nucleotides

Question 3

When does acyclovir become active?

Answer 3

When it comes into contact with thymidine kinase.

Question 4

Explain how Acyclovir is activated.

Answer 4

1. Inactive acyclovir enters the cell but is activated in the presence of thymidine kinase. It forms Acyclo-guanosine monophosphate.
2. Acyclo-GMP is converted into acyclo-guanosine diphosphate using guanylate kinase of the host cell.
3. Acyclo-GDP is then converted to acyclo-guanosine triphosphate by phosphotransferases.

ACYCLO-GTP is ACTIVE

4. Acyclo-GTP works well with viral DNA polymerase but works poorly with host polymerase.

Question 5

So how does acyclovir work then?

Answer 5

1. Acyclo-GTP works well with viral DNA polymerase.
2. It therefore gets incorporated into viral DNA.
3. It doesn’t have a 3’ hydroxyl group, so it cannot continue the chain and join onto another phosphate of a different nucleotide.
4. DNA strand terminates and prevents production of viral DNA.