Acyclovir

Chemical Structure / Formula of Acyclovir

• Formula: C8H11N5O3

• Structure: A purine nucleoside analog (acyclic guanosine derivative).

Mechanism of Action

• Prodrug activated by viral thymidine kinase (TK) to acyclovir monophosphate.

• Further phosphorylated to acyclovir triphosphate, which inhibits viral DNA polymerase and causes chain termination.

Uses

• HSV-1, HSV-2 (herpes labialis, genital herpes, encephalitis).

• Varicella-zoster virus (chickenpox, shingles).

• CMV prophylaxis in immunocompromised patients.

Side Effects

• Nephrotoxicity (crystal nephropathy, reversible).

• Neurotoxicity (seizures, hallucinations in high doses).

• GI distress, headache, rash.

Structure-Activity Relationship (SAR) of Acyclovir

Structural Feature	SAR Insight
Acyclic guanine analog	Mimics guanosine but lacks proper sugar, causing chain termination upon incorporation into viral DNA.
Free hydroxyl group on side chain	Allows phosphorylation by viral thymidine kinase (TK) – critical for selective activation in infected cells.
Guanine base	Essential for recognition by viral enzymes.
Absence of full sugar ring	Causes premature DNA chain termination – key mechanism of action.
Modifications to side chain	Often reduce selective phosphorylation and potency.

Synthesis of Acyclovir