SOME NUCLEOSIDE ANALOGS WITH ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY INHIBIT REPLICATION OF EPSTEIN-BARR-VIRUS

The effects of (+)-beta-D-dioxolane-cytosine ((+)-D-beta-DOC), (-)-bet a-L-dioxolane-cytosine ((-)-L-beta-DOC), (+)-beta-D-oxathiolane-cytosi ne ((+)-D-beta-OTC), (-)-beta-L-oxathiolane-cytosine ((-)-L-beta-OTC, or 3TC), 3'-azido-2',3'-dideoxy-5-methyl-cytidine (5-Me-AZDC), and 3'- azido-2',3'-dideoxyuridine (AZDU) on Epstein-Barr virus (EBV) DNA repl ication in vitro were tested in P3HR-1 cells. Two anti-EBV drugs, 3'-a zido-3'-deoxythymidine (AZT) and 9-(1,3-dihydroxy-2-propoxymethyl)guan ine (DHPG, or ganciclovir), were used as positive controls. The inhibi tory effects on EBV DNA synthesis were quantified by membrane filter a nd Southern blot hybridizations with an EBV-specific probe BamHI-W fra gment. The 50% effective doses (ED(50)) for EBV DNA replication were 0 .15, 0.83, 1.5, 8.3, 14, and 7.7 mu M for DHPG, (-)-L-beta-DOC, (+)-D- beta-DOC, (+)-D-beta-OTC, (-)-L-beta-OTC, and AZT, respectively. In co ntrast, 5-Me-AZDC and AZDU were not effective at concentrations as hig h as 30 mu M. These results indicated that both (-)-L-beta-DOC and (+) -o-beta-DOC were more potent than AZT, which has previously been shown to have anti-EBV activity. (-)-L-beta-DOC and (+)-D-beta-DOC have als o been previously demonstrated to suppress the infectivity of human im munodeficiency virus type 1 (HIV-1). Thus, (-)-L-beta-DOC represents t he first nucleoside analog with L-configuration exhibiting significant antiviral activities against both EBV and HIV.