Some nucleoside analogs with anti-human immunodeficiency virus activity inhibit replication of Epstein-Barr virus

Abstract

The effects of (+)-β- d-dioxolane-cytosine ((+)- d-β-DOC), (−)-β- l-dioxolane-cytosine ((−)- l-β-DOC), (+)-β- d-oxathiolane-cytosine ((+)- d-β-OTC), (−)-β- l-oxathiolane-cytosine ((−)- l-β-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 replication in vitro were tested in P3HR-1 cells. Two anti-EBV drugs, 3′-azido-3′-deoxythymidine (AZT) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, or ganciclovir), were used as positive controls. The inhibitory effects on EBV DNA synthesis were quantified by membrane filter and Southern blot hybridizations with an EBV-specific probe BamHI-W fragment. The 50% effective doses (ED 50) for EBV DNA replication were 0.15, 0.83, 1.5, 8.3, 14, and 7.7 μM for DHPG, (−)- l-β-DOC, (+)- d-β-DOC, (+)- d-β-OTC, (−)- l-β-OTC, and AZT, respectively. In contrast, 5-Me-AZDC and AZDU were not effective at concentrations as high as 30 μM. These results indicated that both (−)- l-β-DOC and (+)- d-β-DOC were more potent than AZT, which has previously been shown to have anti-EBV activity. (−)- l-β-DOC and (+)- d-β-DOC have also been previously demonstrated to suppress the infectivity of human immunodeficiency virus type 1 (HIV-1). Thus, (−)- l-β-DOC represents the first nucleoside analog with l-configuration exhibiting significant antiviral activities against both EBV and HIV.