(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)-cyclobutyl] guanine [(+-)-BHCG or SQ 33,054]: a potent and selective inhibitor of herpesviruses

Antiviral Res. 1990 Jan;13(1):41-52. doi: 10.1016/0166-3542(90)90043-7.

Abstract

(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl] guanine [(+-)-BHCG or SQ 33,054] is a newly synthesized nucleoside analog with potent and selective antiviral activity against members of the herpesvirus group, including human cytomegalovirus. The activity against a thymidine kinase deficient HSV-2 mutant was 25-fold poorer than against the parent virus, suggesting that phosphorylation is an important prerequisite for antiviral activity against HSV-2. (+-)-BHCG is readily phosphorylated by purified HSV-1 thymidine kinase, and BHCG triphosphate synthesized enzymatically is a selective inhibitor of HSV-1 DNA polymerase. (+-)-BHCG did not inhibit host cell growth at concentrations at least 1000-fold higher than HSV-2 inhibitory concentrations. Subcutaneous administration of (+-)-BHCG was protective against HSV-1 systemic infections in mice. BHCG is an exciting antiviral agent and represents a new class of nucleoside analogs.

Publication types

  • Comparative Study

MeSH terms

  • Acyclovir / metabolism
  • Acyclovir / pharmacology
  • Acyclovir / therapeutic use
  • Animals
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • DNA Replication / drug effects
  • DNA-Directed DNA Polymerase
  • Dogs
  • Exodeoxyribonucleases / antagonists & inhibitors*
  • Female
  • Ganciclovir / pharmacology
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • HeLa Cells / drug effects
  • Herpes Simplex / drug therapy
  • Humans
  • Mice
  • Nucleic Acid Synthesis Inhibitors*
  • Phosphorylation
  • Simplexvirus / drug effects*
  • Simplexvirus / enzymology
  • Thymidine Kinase / metabolism
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / metabolism
  • Viruses / drug effects

Substances

  • Antiviral Agents
  • Nucleic Acid Synthesis Inhibitors
  • Viral Proteins
  • Guanine
  • lobucavir
  • Thymidine Kinase
  • DNA-Directed DNA Polymerase
  • Exodeoxyribonucleases
  • DNA polymerase, Simplexvirus
  • Ganciclovir
  • Acyclovir