Inhibition of hepatitis-B-virus DNA polymerase by phosphonoformate: studies on its mode of action

Phosphonoformate (PFA) and phosphonoacetate (PAA) were tested for their ability to inhibit the hepatitis-B-virus associated DNA polymerase. The HBV DNA polymerase was inhibited by 100 microM/liter PFA 50% while it was highly resistant to PAA. The inhibition of the Dane particle-associated DNA polymerase by PFA was not competitive to substrates and not affected by changes in the magnesium concentration. PFA was active also after initiation of the DNA polymerase reaction. Competition studies revealed that PFA had a higher affinity to a proposed pyrophosphate binding site than PAA or--alternatively--that both compounds bind to different sites.