Question

"When replication needs to end" (1.5 pts.) A very popular drug in the treatment of the herpes simplex virus (HSV-1) is called acyclovir. When it comes to the treatment of HIV, the virus that causes AIDS, the most popular drug of choice is AZT (Retrovir). HO HN H HN -OH AZT Acyclovir a) Explain why these drugs are called nucleoside analogues and which nucleotides these are analogues of? (0.5 pt.) b) Hypothesize how each of these drugs might be affecting the DNA replication of the viruses they are meant to target. Use a drawing to aid in your answer. (1 pt.) Interesting side note: Acyclovir and many of the nucleoside analogue drugs are actually derived from natural products- in this case, the sponge Tectitethva crypta.

Answer 1

1) Nucleotide contain 5 carbon sugar, nucleobase and a phosphate group, Nucleosides do not contain the phosphate. Nucleoside analogues are compounds very similar to nucleosides but instead do not function properly.

For example

Aciclovir is an analogue of Guanosine but instead of a full sugar, the structure is missing in aciclovir.

AZT is a thymidine analogue

2) The analogues are structurally very similar to nucleotides but they have missing functionality.

The polymerase confuses them with actual nucleotides and incorporates them with DNA.

For example aciclovir once incorporated in exchange for guanine acts as a chain terminator and stops viral polymerase.

Here is guanosine

N NH НО. 'N NH2 ОН ОН

here is aciclovir

N -NH NH2 -N HO N

Image source (open source commons)

Notice how the sugar is cut off. This means its similar to guanosine but doesn't function like it. Causing transcriptional termination.