Ganciclovir--activation by thymidine kinase, confusion

[str8flexed]

I've heard that Ganciclovir does not need to be activated by the viral thymidine kinase so that that is one of the reasons it is most toxic to humans vs Acyclovir; however, I have also heard that it, too, like Acyclovir, requires activation.

Or is it that Ganciclovir does not need to be activated by a "virus-specific" thymidine kinase? Whatever that means?

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[Mortal_Lessons]

I've heard that Ganciclovir does not need to be activated by the viral thymidine kinase so that that is one of the reasons it is most toxic to humans vs Acyclovir; however, I have also heard that it, too, like Acyclovir, requires activation.

Or is it that Ganciclovir does not need to be activated by a "virus-specific" thymidine kinase? Whatever that means?

My understanding is that Ganciclovir is different than Acyclovir in that it is not as virus-specific, meaning that it has more promiscuity in which thymidine kinases can activate it. This means that viruses which have mutations in their thymidine kinases that render them resistant to Acyclovir might still be susceptible Ganciclovir. The benefit of Ganciclovir is a broader spectrum of viruses (including those that are resistant to Acyclovir)-the cost of course is that cells that are not virally infected might be damaged because normal cell thymidine kinases may activate this nucleotide analog and incorporate it into the DNA.