Phosphonoformate inhibits reverse transcriptase

J Gen Virol. 1979 Nov;45(2):273-81. doi: 10.1099/0022-1317-45-2-273.


The new antiviral substance phosphonoformate (PFA) has been tested in a cell-free system for its effect on reverse transcriptases from an avian retrovirus (avian myeloblastosis virus, AMV) and from mammalian retroviruses (Rauscher leukaemia virus, RMuLV; bovine leukaemia virus; baboon endogenous virus; simian sarcoma virus; visna virus). The observed inhibitory effect of PFA has been compared with that of a structurally related substance, phosphonoacetate (PAA). Phosphonoformate, at a concentration of 100 microM, reduced the activities of all the above mentioned polymerases by 90% when (rA)n.(dT)10 was used as a template/primer. The dose-response curves for AMV and RMuLV polymerases primed with (rA)n.(dT)10 showed PFA to be a 1000-fold more active than PAA; the RMuLV polymerase activity was reduced to 50% after incubation with 0.7 microM-PFA and 0.7 mM-PAA, respectively. There was no difference in PFA inhibition of virus-associated and purified reverse transcriptase activity. Results with various synthetic templates showed that both the RNA- and the DNA-dependent polymerase activities of reverse transcriptase were inhibited by PFA. The endogenous polymerase activity of AMV was inhibited to 50% at 100 microM-PFA, while PAA had no effect. The PFA inhibition was dependent on whether Mg2+ or Mn2+ was used as divalent cation in the assay. Phosphonoformate arrested DNA synthesis immediately after being added to the assay system. The mechanism of inhibition of the AMV polymerase was non-competitive with respect to substrate and template and the apparent inhibition constants were 16 microM and 9 microM, respectively.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiviral Agents*
  • Avian Myeloblastosis Virus / enzymology
  • Foscarnet
  • Haplorhini
  • Leukemia Virus, Bovine / enzymology
  • Magnesium / pharmacology
  • Manganese / pharmacology
  • Organophosphorus Compounds / pharmacology*
  • Papio / microbiology
  • Phosphonoacetic Acid / analogs & derivatives
  • Phosphonoacetic Acid / pharmacology*
  • RNA-Directed DNA Polymerase / metabolism
  • Rauscher Virus / enzymology
  • Retroviridae / enzymology
  • Reverse Transcriptase Inhibitors*
  • Sarcoma Virus, Woolly Monkey / enzymology
  • Templates, Genetic
  • Visna-maedi virus / enzymology


  • Antiviral Agents
  • Organophosphorus Compounds
  • Reverse Transcriptase Inhibitors
  • Foscarnet
  • Manganese
  • RNA-Directed DNA Polymerase
  • Magnesium
  • Phosphonoacetic Acid