eMedExpert Home > Facts > Acyclovir (Zovirax)

Acyclovir was the first successful antiviral agent in the world. It was originally synthesized in 1974 by Howard Schaeffer at Wellcome Research Laboratories (now GlaxoSmithKline). After Schaeffer's discovery, Gertrude B. Elion and her team went to work, studying how it worked, why it worked, and why it was so nontoxic. They discovered that acyclovir remains inert until it meets the herpes virus.

For four years, from 1974 to 1977, more than seventy-five researchers kept acyclovir secret. The first report detailing the selective antiviral activity of acyclovir against herpes viruses was published in 1977 2.

Acyclovir got FDA approval and was released commercially in 1982. It was marked under the trade name Zovirax by the Burroughs Wellcome Company. The original formulation was a topical ointment. Acyclovir became available in oral formulation (200 mg capsules) in 1985 6.

• Oral
• Initial genital herpes
• Recurrent genital herpes
• Herpes zoster infections (shingles)
• Chickenpox (varicella)
• Topical
• Recurrent herpes labialis (cold sores)
• Parenteral
• Herpes simplex, mucosal and cutaneous
• Severe initial episodes of genital herpes
• Herpes simplex encephalitis
• Neonatal herpes simplex infection
• Varicella-zoster (shingles) infections

• Prevention of HSV-2 transmission 13
• Cytomegalovirus infection and disease after organ transplantation 9
• Herpes simplex virus infection after organ transplantation 10, 11
• Ocular herpes simplex 15
• Herpes zoster ophthalmicus 17
• Varicella pneumonia16
• Infectious mononucleosis 4
• Reduces the need for cesarean delivery for recurrent herpes in women whose first clinical episode of genital herpes occurred during pregnancy 18.

Acyclovir exhibits activity against four of the five major herpes-group viruses:

• Herpes simplex virus type 1 (HSV-1) 7
• Herpes simplex virus type 2 (HSV-2) 7
• Varicella zoster virus (VZV) 7
• Epstein-Barr virus (EBV)5, 7
• Cytomegalovirus (CMV) (poor activity) 7, 8

Advantages:

• high efficacy against HSV and VZV infections
• very effective for the suppression of recurrent genital herpes - reduces recurrence by about 90%
• excellent clinical safety profile 6
• minimal toxicity - acyclovir cannot interfere with DNA synthesis in cells that are not infected with the virus
• well-tolerated by most patients
• highly effective for suppression of HSV shedding 13, 14
• considered safe for the mother and baby during pregnancy (so far, no adverse outcomes in the fetus or newborn have been reported)
• minor risk of drug interactions
• inexpensive

Disadvantages:

• low bioavailability (15-30%)
• inconvenient frequent dosing regimen (4-5 times) because the half-life is less than 4 hours
• risk of renal failure and neurotoxicity 12
• does not eradicate latent virus

Acyclovir is a synthetic purine nucleoside analogue with inhibitory activity against herpes simplex virus types 1, 2, and varicella-zoster virus. In simple words, it is so similar to substance that the herpes virus needs for reproduction that the virus is deceived and commits suicide.

The inhibitory activity of Acyclovir is highly selective. It is converted to acyclovir monophosphate by virus-specific enzymes thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes.

Acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase.

The greater antiviral activity of Acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral thymidine kinase.

Acyclovir has a short half-life about 2.5 to 3.3 hr.

• Acyclovir (Zovirax) versus

• 1. Physicians’ Desk Reference, 54th ed; Medical Economics, Thomson Healthcare: Montvale, NJ; 2000.
• 2. Elion, G. B., P. A. Furman, J. A. Fyfe, P. de Miranda, L. Beauchamp, and H. J. Shaeffer. 1977. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. USA 74:5716-5720.
• 3. Darby, G. 1995. In search of the perfect antiviral. Antiviral Chem. Chemother. 6(Suppl. 1):54-63.
• 4. Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother. 1983 Sep;12 Suppl B:113-21.
• 5. Datta AK, Colby BM, Shaw JE, Pagano JS. Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci USA. 1980 Sep;77(9):5163-6.
• 6. Tilson HH, Engle CR, Andrews EB. Safety of acyclovir: a summary of the first 10 years experience. J Med Virol. 1993;Suppl 1:67-73. PubMed
• 7. Collins P. The spectrum of antiviral activities of acyclovir in vitro and in vivo. J Antimicrob Chemother. 1983 Sep;12 Suppl B:19-27.
• 8. Freitas VR, Smee DF, Chernow M, Boehme R, Matthews TR. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses. Antimicrob Agents Chemother. 1985 Aug;28(2):240-5.
• 9. Legendre C, Ducloux D, Ferroni A, Chkoff N, Geffrier C, Rouzioux C, Kreis H. Acyclovir in preventing cytomegalovirus infection in kidney transplant recipients: a case-controlled study. J Med Virol. 1993;Suppl 1:118-22. PubMed
• 10. Lundgren G, Wilczek H, Lönnqvist B, Lindholm A, Wahren B, Ringdén O. Acyclovir prophylaxis in bone marrow transplant recipients. Scand J Infect Dis Suppl. 1985;47:137-44. PubMed
• 11. Pettersson E, Eklund B, Hockerstedt K, Salmela K, Ahonen J. Acyclovir and renal transplantation. Scand J Infect Dis Suppl. 1985;47:145-8. PubMed
• 12. Johnson GL, Limon L, Trikha G, Wall H. Acute renal failure and neurotoxicity following oral acyclovir. Ann Pharmacother. 1994 Apr;28(4):460-3.
• 13. Wald A, Zeh J, Barnum G, Davis LG, Corey L. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):8-15. PubMed
• 14. Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD. Obstet Gynecol. 2003 Dec;102(6):1396-403. PubMed
• 15. Oral acyclovir for herpes simplex virus eye disease: prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000 Aug;118(8):1030-6. PubMed
• 16. El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis. 1998 Jan-Mar;2(3):147-51. PubMed
• 17. Hoang-Xuan T, Büchi ER, Herbort CP, Denis J, Frot P, Thénault S, Pouliquen Y. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology. 1992 Jul;99(7):1062-70 PubMed
• 18. Scott LL, Sanchez PJ, Jackson GL, Zeray F, Wendel GD Jr. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstet Gynecol. 1996 Jan;87(1):69-73.

Published: March 31, 2008
Last updated: December 22, 2011