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Due to the reported synergy between acyclovir [9-(2-hydroxyethoxymethyl)guanine] and 3′-azido-3′-deoxythymidine (AZT) against the replication of human immunodeficiency virus (HIV) in vitro, we have examined several guanosine and other nucleoside analogues for anti-HIV activity. Four of these (2′,3′-dideoxycytidine, Carbovir, 3′-azido,-2′,3′-dideoxyguanosine, and 2′,3′-dideoxyguanosine) had EC 90 s of 1–4 μm in the C3 T-cell line, and three (2′,3′-dideoxyinosine, 2′,3′-dideoxyadenosine, and 2′,3′-dideoxyriboside of 2,6-diaminopurine) had EC 90 s of about 30 μm, in contrast to acyclovir with an EC 50  of &gt;90 μm. Acyclovir and AZT showed only additive to antagonistic effects in this cell line, with the majority of the combination indices greater than 1.0 by both reverse transcriptase activity and p24 antigen data. Additive to antagonistic effects were also produced by this combination in the Jurkat and CEM T-cell lines. Neither 3′-azido-2′,3′-dideoxyguanosine nor 2′,3′-dideoxyguanosine showed synergism with AZT in Jurkat, CEM or C3 cells.

antiviral chemistry and chemotherapy

Inhibition of Human Immunodeficiency Virus Type 1 Replication by Guanosine Analogues and Lack of Synergistic Antiviral Effect of Acyclovir with 3′-azido-3′-deoxythymidine