Inhibitory Effects ofAcyclic Nucleoside Phosphonates on HumanHepatitis BVirus andDuckHepatitis BVirus Infections inTissue Culture

and(S)-1-(3-hydroxy-2phosphonylmethoxypropyl)cytosine onhumanhepatitis Bvirus replication inthehumanhepatoma cell line HepG22.2.15 andduckhepatitis Bvirus infection inprimary duckhepatocytes wereinvestigated. (R)-9-(2phosphonylmethoxypropyl-2,6-diaminopurine hadthelowest 50%o inhibitory concentrations against hepatitis B virus andduckhepatitis Bvirus, 0.22 and0.06,iM, respectively, i.e., two-tofivefold lower concentrations than required for(R)-9-(2-phosphonylmethoxypropyl)adenine and9-(2-phosphonylmethoxyethyl)adenine. Allcompounds werenottoxic invitro ataconcentration of100,uM. Inchronic hepatitis Bvirus (HBV)infection thebasic therapy istheadministration ofinterferon, although complete disappearanceofvirus markers isseldom observed. Hepatitis Beantigen seroconversion, reflecting adrastic decline ofviral replication, isseeninonly 20to40%ofpatients withHBV infections. Morepotent antiviral drugs areeagerly awaited, andinlight ofthis, theacyclic nucleoside phosphonates described earlier (3,4)wereconsidered adequate candidates tobefurther pursued forthetreatment ofHBV infections. Inanearlier study (6) weinvestigated theacyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) intwohepatoma cell lines andprimary duckhepatocytes. The 50%inhibitory concentrations (IC50) forhumanHBV and duckHBV (DHBV)werefoundtobe1.2and0.2,uMas measured inHepG22.2.15 cells andprimary duckhepatocytes, respectively. Amongtheacyclic nucleoside phosphonates several other