Antiherpetic properties of acyclovir 5'-hydrogenphosphonate and the mutation analysis of herpes virus resistant strains

Chem Biol Drug Des. 2009 Oct;74(4):382-9. doi: 10.1111/j.1747-0285.2009.00874.x. Epub 2009 Aug 19.


In this study, we continued to study antiherpetic properties of acyclovir 5'-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. Hp-ACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1/L(2) strain. The compound suppressed replication of both ACV-sensitive HSV-1/L(2) and ACV-resistant HSV-1/L(2)/R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1/L(2)/R(Hp-ACV)) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1/L(2)/R(Hp-ACV) population demonstrated their partial cross-resistance to ACV. The mutations determining the resistance of HSV-1 clones to Hp-ACV were partly overlapped with mutations defining ACV resistance but did not always coincide. HSV-1/L(2)/R(Hp-ACV) herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / analogs & derivatives*
  • Acyclovir / chemical synthesis
  • Acyclovir / chemistry
  • Acyclovir / pharmacology
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Drug Resistance, Viral
  • Herpesviridae / drug effects
  • Herpesviridae / genetics*
  • Herpesviridae Infections / drug therapy
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mutation
  • Sequence Alignment
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Vero Cells


  • Antiviral Agents
  • Thymidine Kinase
  • Acyclovir