Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues.

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Abstract
Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)[adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simples virus (HSV), but the more active inhibitor of the deaminase, 2''-deoxycoformycin, does not. At 10 .mu.M EHNA, which does not affect viability, growth, or DNA synthesis of uninfected [human cervical carcinoma] HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 6%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 .mu.M) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3''-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 .mu.M) does not inhibit HSV replication but in combination with 10 .mu.M EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% but protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in 2 different ways, depending on whether it is used alone or in the presence of cordycepin.