Acyclovir: Discovery, mechanism of action, and selectivity

  title={Acyclovir: Discovery, mechanism of action, and selectivity},
  author={Gertrude Bell Elion},
  journal={Journal of Medical Virology},
  • G. Elion
  • Published 1993
  • Biology
  • Journal of Medical Virology
The reasons for acyclovir's activity and selectivity in cells infected with HSV or VZV may be summarized as follows: 1. Activation by a HSV- or VZV-specified TK. 2. Greater sensitivity of viral DNA polymerase than of the cellular polymerases to ACV-TP. 3. Inactivation of the viral DNA polymerase, but not the cellular polymerases, by ACV-TP. 4. Chain termination of viral DNA by incorporation of ACV-MP. For the Epstein-Barr virus, which is also sensitive to acyclovir, there is no selective… 

Separation methods for acyclovir and related antiviral compounds.

Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management

The gold standard phenotypic method for evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque reduction assay and there is a need to develop new antiherpetic compounds with different mechanisms of action.

Substrate specificity and molecular modelling of the feline herpesvirus-1 thymidine kinase

Three-dimensional model of this enzyme was constructed based on sequence homology with two other herpesviral TKs, encoded by equine herpesvirus-4 (EHV-4) and herpes simplex-1 (HSV-1), and identified two residues as being critical for the differential ability of this enzymes to phosphorylate nucleoside analogues.

Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir.

The nucleotide changes of the DNA polymerase gene and the susceptibility of acyclovir (ACV)-resistant varicella-zoster virus (VZV) mutants to anti-herpetic drugs were determined and compared to those

Susceptibilities of Herpes Simplex Viruses to Penciclovir and Acyclovir in Eight Cell Lines

Among the transformed cell lines producing well-defined plaques, A549 cells provided the best concordance between IC50s for the two HSV types and two antiherpes drugs.

Herpes simplex virus resistance to antiviral drugs.

  • F. MorfinD. Thouvenot
  • Biology, Medicine
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
  • 2003

Antiviral Drugs Against Herpesviruses.

  • J. PiretG. Boivin
  • Biology, Medicine
    Advances in experimental medicine and biology
  • 2021
The discovery of the nucleoside analogue, acyclovir, represented a milestone in the management of infections caused by herpes simplex virus and varicella-zoster virus and constituted the second-line antiviral drugs, however, the viral DNA polymerase is the ultimate target of all these antiviral agents.

New Antiherpesvirus Agents

Toxic issues continue to be problematic in the anti-CMV arena, although newer agents have improved the situation to some extent, and safety standards must be met by newer agents entering the field.



Mechanism of action and selectivity of acyclovir.

  • G. Elion
  • Biology, Chemistry
    The American journal of medicine
  • 1982

Acyclovir inhibition of Epstein-Barr virus replication.

The results suggest that a competitive mechanism is the major mode of acyclovir inhibition of EBV replication, and the virus-producing cell line P3HRF-1 consistently shows reduced viral genome numbers and viral capsid antigen on prolonged exposure to acyClovir.

In vitro susceptibility of varicella-zoster virus to acyclovir

Analysis of the metabolism of acyclovir in varicella-zoster virus-infected WI-38 cells revealed that, as with herpes simplex virus types 1 and 2, the formation of the triphosphate forms of the drug is specific to viral infection.

Acyclovir-resistant mutants of herpes simplex virus type 1 express altered DNA polymerase or reduced acyclovir phosphorylating activities

The biochemical properties of four acyclovir-resistant mutants are described. Two of these mutants, PAAr5 and BWr, specified nucleotidyl transferase (DNA polymerase) activities which were less

Acyclovir transport into human erythrocytes.

Herpes simplex virus type 1 DNA polymerase. Mechanism of inhibition by acyclovir triphosphate.

Studies indicated that potent, reversible inhibition by ACVTP and the next required deoxynucleoside 5'-triphosphate also occurred when poly(dC)-oligo(dG) or activated calf thymus DNA were used as the template-primer, and the reversibility of the dead-end complex was demonstrated.

Inhibition of cellular alpha and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir

Human cytomegalovirus and the H29R strain of herpes simplex virus type 1, however, were found to be relatively insusceptible to acyclovir, even though their induced DNA polymerases were inhibited by low concentrations of acyClo-GTP.

Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines

Neither the productive replication of EBV nor the presence of latent viral DNA is required for ACV monophosphate formation in B lymphoblastoid cells and ACV triphosphate was detected only in cells infected productively with EBV.

Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase.

Common product analysis of the two alternative substrates, 6-thioguanosine-B'-P and acyclo-GMP, indicated that a single enzyme was responsible for the phosphorylation of both compounds.