Question

Which is the active form of Ganciclovir?

• A. Phosphate
• B. . Tetraphosphate
• C. Biphosphate
• D. Triphosphate

Answer 1

The Correct Option is D

The correct option is (D): Triphosphate.

Answer 2

Ganciclovir is an antiviral prodrug that needs to be converted inside infected cells before it can act on viral DNA polymerase. The question asks which converted form actually does the work.

1. Phosphate: The monophosphate form is only the first step of activation, produced when a viral or cellular kinase adds a single phosphate group. On its own it is not yet able to compete effectively with the natural nucleotide at the DNA polymerase active site.
2. Tetraphosphate: Ganciclovir's activation pathway does not proceed to a four-phosphate form; nucleoside analogues in this class are only ever converted up to a triphosphate, so a tetraphosphate species does not form as part of its mechanism.
3. Biphosphate: A diphosphate (biphosphate) intermediate does form during activation, but it is still one phosphorylation step short of the fully active species, and it is not the form that goes on to inhibit viral DNA polymerase.
4. Triphosphate: Cellular kinases add two more phosphate groups after the initial monophosphate step, producing ganciclovir triphosphate. This triphosphate form is structurally similar enough to deoxyguanosine triphosphate that viral DNA polymerase incorporates it into replicating viral DNA, which then stops the DNA chain from extending further and halts viral replication.

Since only the fully triphosphorylated form is close enough to a natural nucleotide to be incorporated by viral DNA polymerase and block replication, that is the active species.

The correct answer is Triphosphate.