Tutorial 1 - Acyclovir, an antiviral agent

Question 1

What is Acyclovir?

Answer 1

Antiviral used to treat Herpes.

Question 2

Define these key terms -

selective toxicity
Kinase
Thymidine Kinase
Nucleoside
Nucleoside Analogue?

Answer 2

1. selective toxicity - acyclovir doesnt affect host cell
2. kinase - enzyme that phosphorylates
3. thymidine kinase - enzyme which makes the protein coat
4. nucleoside - nucleotide with no phosphate
5. nucleoside analogue - molecule that acts like nucloeside in DNA synthesis. Large group of antivirals.

Question 3

Virus Life Cycle

Answer 3

1. virus enters host cell and breaks protein coat releasing viral dna.
2. some dna is replicated and other is transcribed.
3. mRNA from transcription is translated to produce protein for coat.
4. protein coat and the DNA from replication assemble and exit to form new virus particles.

Question 4

Summarise DNA replication?

Answer 4

DNA has to unravel first, using enzyme TOPOISOMERASE

DNA HELICASE breaks the hydrogen bonds

DNA polymerase synthesises new strand

DNA LIGASE joins new strand to original strand.

Question 5

how is viral polymerase different to dna polymerase

Answer 5

3’ OH group has to be phosphorylated so it can join the next nucleotide and continue the polynucleotide chain.

Acyclovir is similar to deoxyguanosine but DOESN’T HAVE THE 3’ OH group. Therefore it cannot attach other nucleotides.

In this way it cant continue the chain and join onto another phosphate of a different nucleotide so the DNA strand terminates and prevents production of viral DNA.

Question 6

How is acyclovir activated?

Answer 6

It’s given in the inactive form and only activated when in contact with Thymidine Kinase (only present in cells where virus has invaded and released thymidine kinase.

In these cells it forms Acyclo-guanosine monophosphate (acyclo-gmp)
Converted in to Acyclo-GDP using guanylate kinase of the host cell.
Then into Acyclo-GTP by phosphotransferases (ACTIVATED)