Antiviral agents

Question 1

Acyclovir (Zovirax) characteristics

Answer 1

Analogue of deoxyguanosine (acyclic side chain, lacks 3’hydroxyl, chain terminator of viral DNA synthesis)

Question 2

Specificity for viral DNA of acyclovir

Answer 2

ACV requires phosphorylation to be active, initial step accomplished by HSV viral thymidine kinase (human cell enzymes activate ACV inefficiently, phosphorylated mainly in virus infected cells/it is selective)

Also has a greater affinity for viral polymerase vs cellular polmerase (greater effects on viral replication, less on hoss cell DNA synthesis)=less cell toxicity

Question 3

Steps in acyclovir within the cell

Answer 3

1. Acyclovir gets in the cell
2. Acyclovir is activated by viral thymidine kinase (enzyme of virally infected cells)
3. Cellular kinases make the drug an aciclovir triphosphate

Question 4

Drug activity of acyclovir

Answer 4

Very effective against HSV-1 and HSV-2. Less active (but usually effective) against VZV. Considered drug of choice for HSV and VZV. Little to no in vivo activity against other herpes