Microbiology
Mechanism of Action
Valacyclovir is a nucleoside analogue DNA polymerase inhibitor. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against HSV types 1 (HSV-1) and 2 (HSV-2) and VZV both in cell culture and in vivo.
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue.
So here is the deal for anyone who is still reading this thread and wants the
real story in terms of Valtrex.
Acyclovir and it's prodrug Valtrex (valacyclovir) are nucleoside analogues, but they are not thymidine analogues, they are guanosine analogues.
http://en.wikipedia.org/wiki/Nucleoside_analogue
These antiviral drugs are very safe because they do not work in healthy cells, they only work in virally infected cells.
The drugs work by inhibiting a
viral enzyme called thymidine kinase.
Now to make matters more complicated, there is also a
cellular thymidine kinase present in healthy cells. But the cellular thymidine kinase are not able to phosphorylate the drugs which is a fancy way to say that the drugs have no effect in healthy cells.
However, in virally infected cells, the drug is able to effect cessation of viral replication.
A nice explanation is here:
Acyclovir undergoes monophosphorylation (adds one phosphate group) catalyzed by a virus-encoded enzyme thymidine kinase. The formation of the monophosphate can only take place in the presence of the virus, thus the drug accumulates as the monophosphate only in infected cells. It is then converted to a diphosphate and triphosphate by “normal” host enzymes in the cell. ACV-triphosphate inhibits the viral DNA polymerase from incorporating guanosine triphosphate and is itself incorporated. The DNA cannot grow further, add more groups and the chain terminates.
The mechanism of action is thus twofold: inhibition of viral DNA polymerase and chain termination of DNA once it has been incorporated into the nucleic acid.
http://www.emedexpert.com/classes/herpes-medications.shtml
So (besides the fact that the article itself states that no conclusions can be drawn as to in vivo mitochondrial toxicity),
Valtrex does not even fall into the class of drugs that are discussed as even *potentially* toxic to the mitochondria.
I actually think it would be interesting to study the antivirals and the mitochondria. But at this point, there is no reason at all to discontinue antivirals based on concerns over toxicity to the mitochondria. There is no evidence to support this position.