👄 Acyclovir & Valacyclovir Therapy Simulator

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.