Description

Acyclovir is a synthetic nucleoside analog that is a potent and highly selective antiviral agent. It is specifically active against viruses of the herpes family, including herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). A key feature of acyclovir is that it is a prodrug that requires activation by a viral enzyme to become effective, which accounts for its high selectivity for infected cells and its low toxicity to host cells. It is available in various forms, including oral tablets, topical creams, and intravenous solutions.

Indications

Acyclovir is indicated for the treatment and prophylaxis of infections caused by herpes viruses. Its key indications include:

• Genital Herpes: For the treatment of initial episodes and the management of recurrent episodes of genital herpes.

• Cold Sores (Herpes Labialis): For the treatment of cold sores caused by HSV.
• Chickenpox (Varicella): For the treatment of chickenpox in adults and children, particularly to reduce the severity and duration of the illness.

• Shingles (Herpes Zoster): For the treatment of shingles to reduce pain and rash duration and to prevent post-herpetic neuralgia.
• Herpes Encephalitis: For the intravenous treatment of herpes encephalitis, a severe brain infection.

• Prophylaxis: To prevent herpes infections in immunocompromised patients, such as those with HIV or those undergoing organ transplants.

Mechanism of Action

Acyclovir’s mechanism of action is highly specific to herpes-infected cells, making it a targeted and safe antiviral.

1. Viral Activation: Acyclovir is a pro-drug. It first enters the infected cells where it is phosphorylated by a viral enzyme called thymidine kinase (TK), which is only present in herpes-infected cells. This phosphorylation is the critical first step. The resulting compound is then further phosphorylated by host cell kinases to form its active metabolite, acyclovir triphosphate.
2. Inhibition of Viral DNA Polymerase: The active form, acyclovir triphosphate, has a very high affinity for the herpes viral DNA polymerase (an enzyme essential for viral replication) but a very low affinity for host cell DNA polymerase.

3. DNA Chain Termination: When the viral DNA polymerase attempts to use acyclovir triphosphate as a building block for a new DNA chain, the compound gets incorporated into the viral DNA. Because acyclovir lacks the necessary chemical structure to allow for further DNA chain elongation, it acts as a chain terminator, permanently halting viral DNA synthesis.

In summary, acyclovir works by being selectively activated by a viral enzyme inside infected cells. Its active form then specifically inhibits the viral DNA polymerase, preventing the virus from replicating its genetic material. This targeted action makes it highly effective against herpes viruses with minimal harm to host cells.