Viral Thymidine Kinase Activation
Placeholder: HSV thymidine kinase phosphorylates acyclovir far faster than host enzymes.
- ~3000×: Selectivity vs host TK (placeholder figure)
- Valacyclovir: Prodrug used (oral bioavailability boost)
- ~55%: Oral bioavailability (placeholder figure)
- Viral TK: Activating enzyme (HSV-1 / HSV-2 / VZV)
Why viral TK matters
Placeholder text: only infected cells efficiently activate the drug.
Valacyclovir as prodrug
Placeholder text: valacyclovir converts to acyclovir after gut absorption.
Selectivity advantage
Placeholder text: this selectivity limits toxicity to healthy tissue.
Triphosphate Conversion Inside Infected Cell
Placeholder: cellular kinases add two more phosphates to form ACV-triphosphate.
- 3: Phosphorylation steps (mono → di → tri)
- ACV-TP: Active metabolite (placeholder figure)
- ~1 h: Intracellular half-life (placeholder figure)
- GMP/NDP kinase: Enzymes involved (host cellular kinases)
Second and third phosphate
Placeholder text: host guanylate and nucleoside kinases finish activation.
Concentration inside cells
Placeholder text: ACV-TP accumulates far higher in infected cells.
Ready for incorporation
Placeholder text: ACV-TP now mimics a natural nucleotide substrate.
DNA Polymerase Inhibition
Placeholder: ACV-TP is incorporated then terminates the growing viral DNA chain.
- 3'-OH: Missing group (chain-terminator)
- Viral DNA pol: Target enzyme (placeholder figure)
- ~100×: Binding affinity (vs host polymerase)
- Chain termination: Effect (placeholder figure)
Chain-terminating nucleotide
Placeholder text: no 3'-OH means no further nucleotides can attach.
Polymerase trapping
Placeholder text: the enzyme gets locked onto the terminated strand.
Replication halted
Placeholder text: viral genome copying stops, limiting viral spread.
Episodic Treatment at Prodrome
Placeholder: starting therapy at first tingling shortens outbreak duration.
- <24 h: Ideal start window (from prodrome onset)
- ~1–2 days: Duration cut (early) (placeholder figure)
- 1–5 days: Typical course (placeholder figure)
- Diminished: Benefit if delayed (placeholder figure)
Prodrome recognition
Placeholder text: tingling or itching signals imminent viral reactivation.
Timing sensitivity
Placeholder text: benefit shrinks the later treatment is started.
Episodic use case
Placeholder text: best suited for infrequent, mild recurrences.
Suppressive Daily Therapy for Frequent Outbreaks
Placeholder: continuous daily dosing keeps drug levels above the inhibitory threshold.
- ~70–80%: Outbreak reduction (placeholder figure)
- ≥6/yr: Typical candidates (recurrence frequency)
- Once daily: Dosing frequency (valacyclovir regimen)
- Also lowered: Transmission reduction (placeholder figure)
Steady-state suppression
Placeholder text: constant drug presence blocks reactivation before spread.
Candidate selection
Placeholder text: reserved for patients with frequent, disruptive outbreaks.
Long-term outlook
Placeholder text: suppressive therapy also reduces asymptomatic viral shedding.