Longterm effects on DNA of aciclovir

Question

Since aciclovir works by decreasing the production of the virus's DNA, one might fear that it also damages DNA of healthy cells. I know that it is usually said that aciclovir doesn't affect healthy cells, but I heared recently rumors that there might be a longterm negative effects on the DNA of the patient.

So my question is the following:

• Are there any scientific studies which evaluated the longterm effects on DNA of aciclovir and what are the results.
• What are the mechanisms which ensure that it indeed doesn't affect healthy cells?

Answer 1

Aciclovir is a prodrug, which means that it has to be converted to an active form before having its desired effect.

It is converted to this active form (aciclovir triphosphate) by a process called phosphorylation. This process requires an enzyme called herpes simplex virus (HSV) thymidine kinase, which competes for endogenous deoxyguanosine triphosphate and acts as a chain terminator in the synthesis of viral DNA. Source: Science Direct

This enzyme is not present in humans, so the conversion does not occur. In viruses, it interferes with DNA synthesis to reduce viral replication.

Incidentally, viral resistance to the drug is due to a mutation in the thymidine kinase enzyme.

There have been studies demonstrating the safety of aciclovir. Here is an example demonstrating safety over a five-year period in the suppression of genital herpes.