EFFECT OF OXETANOCIN-G, A NOVEL NUCLEOSIDE ANALOG, ON DNA-SYNTHESIS BY HEPATITIS-B VIRUS VIRIONS

The novel nucleoside oxetanocin G, -2-hydroxymethyl-beta-D-erythro-oxe tanosyl)guanine (OXT-G), that is a derivative of oxetanocin A, was stu died in relation to its action on the synthesis of hepatitis B virus ( HBV) DNA and cellular DNA in an HBV-producing cell line, HB611 (T. Tsu rimoto, A. Fujiyama, and K. Matsubara, Proc. Natl. Acad. Sci. USA 84:4 44-448, 1987). The median effective concentration of OXT-G against HBV replication was 1.5 muM, and the median cytotoxic concentration was m ore than 1,000 muM. At the same concentration, OXT-G did not inhibit c ellular DNA synthesis or viral RNA synthesis. Chemically synthesized O XT-GTP inhibited the HBV endogenous DNA polymerase reaction and was in corporated into HBV DNA strands at a low efficiency compared with the incorporation of dGTP. A synthetic primer-template study revealed that OXT-GTP was incorporated into DNA strands at a low efficiency and tha t further extension of the DNA strand by using the 2' position of the incorporated OXT-G could take place.