Small molecule
PubChem CID 135398513
Acyclovir
Zovirax
- Mechanism of action
- Viral DNA polymerase inhibitor (guanosine analog)
- In plain language
- Tricks the herpes virus into using a faulty DNA building block, jamming its copying machinery so it can't make more of itself.
- How it works
- Acyclovir is a synthetic acyclic guanosine analogue that must first be phosphorylated by herpesvirus-encoded thymidine kinase, a reaction herpesviruses catalyze far more efficiently than human cells do, which is what makes activation largely virus-selective. Cellular kinases then convert the resulting monophosphate to acyclovir triphosphate, which competitively inhibits viral DNA polymerase, gets incorporated into the elongating viral DNA strand to cause obligate chain termination (it lacks the 3'-hydroxyl needed for further extension), and can inactivate the polymerase directly. Because uninfected cells barely activate the drug, therapeutic concentrations accumulate almost exclusively in infected cells, giving acyclovir a wide safety margin relative to its antiviral effect. This selectivity explains its potency against HSV-1, HSV-2, and VZV and its comparatively weaker activity against viruses that lack an analogous thymidine kinase.
- Therapeutic applications
- FDA-labeled (oral) for the acute treatment of herpes zoster (shingles); treatment of initial episodes and management of recurrent episodes of genital herpes (HSV-1/HSV-2); and treatment of varicella (chickenpox). Injectable acyclovir sodium carries additional indications for mucosal and cutaneous HSV infections in immunocompromised patients, severe initial genital herpes in immunocompetent patients, herpes simplex encephalitis, neonatal HSV infection, and varicella-zoster infections in immunocompromised patients. Topical formulations are indicated for recurrent herpes labialis (cold sores) and, for the ointment, initial genital herpes and limited non-life-threatening mucocutaneous HSV infections in immunocompromised patients.
- Class
- Small molecule
- Therapeutic area
- Antiviral
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